Episode 7: Treatment of Generalized Anxiety Disorder with Dr. Jared Peck

• Episode 7: Treatment of Generalized Anxiety Disorder with Dr. Jared Peck

  Dr. Jordan Bawks: [00:00:10] Welcome to Psyched, the Educational Psychiatry Podcast by Medical Learners for Medical Learners. Thanks for joining us as we continue our series on core topics in psychiatry. This is the second episode in our series on Generalised Anxiety Disorder or as we will commonly refer to it, GAD. Within psychiatry, we use biological, psychological and social model of understanding the illness experience. And today we'll be focusing on a variety of treatment options that help people who are suffering from symptoms of GAD. If you haven't already, I'd recommend you check out part one where we talked about diagnosis, but it's your life and we're happy to have you here. Either way. Your Psyched hosts today are Dr. Jordan Bawks, a second year resident. That's me and Dr. Bruce Fage, fourth year psychiatry resident at the University of Toronto. We are joined by Dr. Jared Peck. Again, last episode we teased you, saying that Jared had done an earlier episode with us, but I'm here to correct that today. This is actually the second episode with Dr. Peck. We're very happy to have him back once again. He is still the head of ambulatory psychiatry at the Mount Sinai Hospital, still an assistant professor at the University of Toronto and still a bike safety enthusiast, especially as the weather warms up here in Toronto. In addition, Dr. Peck is a certified CBT therapist with the Academy of Cognitive Therapy and trained at the Beck Institute for Cognitive Behavioural Therapy. And that's one of the reasons we're so happy to have him here to talk about CBT and anxiety. Thanks for bringing your expertise and clinical experience to talk about GAD with us again. Dr. Peck.

  Dr. Jared Peck: [00:01:47] My pleasure. Thanks for having me back.

  Dr. Bruce Fage: [00:01:50] So in terms of the objectives for this episode, we're going to be focusing on treatment and we're going to focus on things like lifestyle modifications, psychopharmacology, including first line treatments with some second and third line options. After that, we're going to talk about psychotherapy, some different options, though, focusing on cognitive behavioural therapy, and then we'll wrap up, provide you a summary and some additional reading.

  Dr. Jordan Bawks: [00:02:15] So, Dr. Peck, can you walk us through the general approach to treating GAD? For example, if you are working to support a person with GAD, what would you say about the treatment options and process?

  Dr. Jared Peck: [00:02:29] Sure. Well, first and foremost, the foundation of all treatment starts with providing people with just education about their illness. So if we rewind to our last session, those questions and the things we talked about in terms of pathological versus non pathological anxiety, kind of explaining what really the disorder is, is the starting place so people can understand that it's about their worry creeping up when there's less of a need for worry or misinterpreting situations as more dangerous and then experiencing those physical symptoms. So that's the first piece. And then, you know, we'd want to look at lifestyle and from the biopsychosocial perspective, we can look at kind of social or lifestyle things as well as biological and then psychological treatments.

  Dr. Jordan Bawks: [00:03:22] And when you talk to patients about sort of like lifestyle changes and generalised anxiety disorder that have evidence or kind of just make good clinical sense, what are the typical big things that you highlight?

  Dr. Jared Peck: [00:03:34] Well, you know, increasingly we live in a society where everyone's turned on with their phones and always checking them. And I think, you know, there's always this sort of drive that we have and kind of we need to check things, we need to check. So I think turning off a little bit is an important piece, and that can include exercise, yoga, things like that. And there's some evidence for those things as well as it just kind of being, quote, common sense. But lots of things become common sense when you when you after the fact. In addition to that, we want to look at substance use. People are often drinking coffee. Not everyone with anxiety is or with generalised anxiety disorder is super sensitive to the effects of caffeine, but many people are, so the coffee will make them physically feel a bit keyed up or revved up. It's difficult because sometimes people compensate with having coffee because as part of their anxiety they have a hard time sleeping. Which leads us into talking about sleep hygiene. And I don't know if you guys are doing a podcast on sleep hygiene, but you know, the basics of it are making sure you really have this winding down period and keeping the bed for for sleeping. Not a lot of screen time before, not exercise just before bed, you know, not eating too late, not smoking too late, getting out of bed if you're really thinking about something. So there's a bunch of principles there.

  Dr. Jordan Bawks: [00:05:02] So it's sort of like reducing stimulants when possible, like caffeine increasing, kind of like non-electronic, like relaxing, focussed kind of exercises, like exercising or yoga or meditation and also like protecting sleep through sleep hygiene.

  Dr. Jared Peck: [00:05:21] Yeah. And then also people sometimes have a drink of alcohol to wind down and drinking is okay. But again, people with anxiety disorders, one drink might kind of cut the edge off things. But when people drink and then alcohol is getting out of the system, you can have rebound anxiety. And so we really want to educate people around the impact of alcohol on their anxiety.

  Dr. Bruce Fage: [00:05:47] So it sounds like even before we get to medical treatment, there are lots of options for patients to consider in managing their own anxiety and symptoms of generalised anxiety disorder. In terms of medications and psychotherapy, do you have a sense of which one is superior?

  Dr. Jared Peck: [00:06:06] Um, well, there's not clear evidence that one is superior over the other. There's some signal towards psychotherapy being more long lasting, meaning that once you're not engaged in the act of psychotherapy, you continue to have gains. Whereas if you're on medications and you're no longer taking the medications, you don't have gains. So there's a signal that there's more sustained gains. But really the evidence is that both can be helpful. And there's questions around whether a combination can be more helpful or less helpful, paradoxically. But that's the jury's still out on that.

  Dr. Bruce Fage: [00:06:48] Thanks for explaining that. I guess I'm wondering if you can tell us a little bit about some of the medications that you use for treating generalised anxiety disorder.

  Dr. Jared Peck: [00:06:56] Sure. You know, there's there's generally two classes that have the most evidence or technically three classes in terms of response with all medications. We want to look at the individual, we want to look at what potential comorbid conditions they have, if they've had treatment in the past, how they've tolerated that. Look at the potential side effects. And as always, as a reminder, we want to have full informed consent around the risks, benefits, common and very serious side effects. So if we look at probably the most commonly used medications or the ones with the the most commonly used first line medications, those would be the selective serotonin reuptake inhibitors and the serotonin norepinephrine reuptake inhibitors, what we refer to as the SSRIs and SNRIS. These drugs don't work immediately. We start at a lower dose and then try to fairly rapidly, but not too quickly increase them until we hit the therapeutic window and then leave them there for a few weeks and then increase more over time. They can take. People can get early benefits. So in the first 2 to 3 weeks, but often it's 4 to 6 weeks and sometimes with anxiety can be a bit longer, getting closer to eight weeks, which can sometimes be a little bit longer than in treatment of depression, but not always. They're generally well tolerated. The early side effects and the ones that are most common are a lot of gastrointestinal side effects. So like feeling a bit bloated, your bowels, movements changing one direction or the other, or a bit of nausea, that usually settles.

  Dr. Jared Peck: [00:08:56] And that's why we ease people in. People can get a bit of a headache and tremor sometimes, sometimes not. With all of them, but sometimes initially there can be a little bit of a spike in the anxiety. Or it can be what we often refer to as, quote, activating, which is, you know, a bit energising but can sometimes be experienced as some physical anxiety. We tell everyone that you can, with all the SSRI and SNRIs, have changes in your sexual functioning. So it can be anything upon anything along the sexual response curve. So it could be decreased interest kind of taking longer for someone to become physically aroused right through to delays or inability for people to orgasm. It doesn't happen in everyone. It's usually somewhat dose dependent. If it happens with one medication, it's not necessarily going to happen with another one, but that's an important one. With SNRIs, particularly as we increase the dose, they can affect people's blood pressure. So we want to watch that as well. So those are the SSRI and SNRIs. Then there's another class of medications, Alpha two, Delta drug, and that's a medication called Pregabalin. Now, Pregabalin is also first line evidence for GAD. I believe it's used more in Europe than in North America, but I'm not sure what what has led to that prescribing practice. But I think it's increasingly being used here.

  Dr. Jared Peck: [00:10:38] It's clear from studies and from treatment guidelines that it's an effective medication. There's some advantages and disadvantages when we compare Pregabalin to SSRIs. The advantage would be it doesn't have the sexual side effects up front. And probably although SSRIs and SNRIs are well tolerated overall, it's probably a bit better tolerated in terms of having less of those GI symptoms up front, although people can get a bit of that. And one of the disadvantages is that as we talked about previously, a lot of people have comorbid depression or other anxiety disorders, and SSRIs and SNRIs in general are indicated for most anxiety disorders. Pregabalin is not indicated for all anxiety disorders, and in addition, Pregabalin is not an antidepressant. So you lose that that sort of dual treatment. I have found, though, in some people it can be tremendously helpful. There is some evidence for treatment in alcohol use disorders, which is positive. As we know, alcohol use disorders can be comorbid with anxiety and generally there are there are few interactions with Pregabalin. I've kind of gone all over the place with the pros and cons, but another con would be it's more expensive. So, you know, hopefully people have drug coverage. If they don't, then it's going to be quite expensive. And, you know, one of the SSRIs would be where you start. Also, in general, in medicine, we prefer things that are dosed once a day and Pregabalin is b.i.d. Dosing.

  Dr. Bruce Fage: [00:12:40] And just to for our listeners, bid means twice a day.

  Dr. Jared Peck: [00:12:43] Yes.

  Dr. Bruce Fage: [00:12:44] Yeah.

  Dr. Jordan Bawks: [00:12:44] And yeah, it's interesting because it's like it seems like there's a lot of excitement about Pregabalin in the current kind of clinical environment because it's a new kind of class of agent, right? It's, you know, sometimes when you rotate people between SSRIs and SNRIs, you do get a response, right? Like some people will respond to Sertraline when they don't respond to Escitalopram. But I think it's, you know, it's nice to have a totally different class of drug. And the other thing, too, is there seems to be some signal in the literature that people respond to Pregabalin a little bit earlier, like whereas SSRI takes, you know, 4 to 6 weeks or maybe more and anxiety disorders. I think the literature kind of supports that. In Pregabalin, you can see it within like 1 to 2 weeks if you're doing a rapid titration.

  Dr. Jared Peck: [00:13:27] Anecdotally, I would say that in my experience I've prescribed more SSRI or SNRIs over time for anxiety than Pregabalin. But when I've had people improve, the improvement has been earlier. So I would agree with that.

  Dr. Jordan Bawks: [00:13:49] And I think too, because people generally get less exposure to Pregabalin, they may be less comfortable with dosing. And it's worth noting that there's for people who are interested in the evidence that supports Pregabalin, there's a great systematic review and meta analysis by Generoso.  We'll put that in our show notes. It was done in 2017 and I was looking at the dosage ranges and it's anything from like 150 to 600. And they also look at the tolerability, the compared to Benzodiazepines. So again, you're looking in that 150 to 600 kind of dosage range, which you'll find in most sort of clinical practice recommendations. And but usually when you get above like 150, you need to do bid and it's a short acting drug. So especially you need to do it twice a day because it doesn't last in your system long enough. Another thing that I'm almost like reticent to mention on a podcast that goes out to the broader public, but I think it's worth knowing for prescribers that there does seem to be some case reports of people abusing Pregabalin as well, like it's a sedative medication that acts fast. And so when you're prescribing it, you should watch for kind of like signals of misuse, people running out early or asking for dosage ranges that aren't clinically indicated. So something for prescribers to be aware of.

  Dr. Jared Peck: [00:15:11] Yeah. And and a lot with respect to the sedative aspect, particularly as you increase the dose with the bid dosing, sometimes that can get get in the way a little bit. If someone's up to, you know, 200, 300 or even. Yeah, yeah. Around that much in the morning can can be a bit sedating but not in everyone.

  Dr. Jordan Bawks: [00:15:33] And also something that we don't often think about with the SSRIs is kidney function. So if you have a patient who has like medical comorbidities, it's important to check their creatinine clearance because that's how Pregabalin gets out of the system. So you could you might need to adjust dosing based on that.

  Dr. Jared Peck: [00:15:48] Yes. Now, there's a couple other drugs that we see used. Quetiapine seems to be the pandiagnostic drug or in regular terms the drug that's used for everything. And there  it doesn't have first line evidence as being a drug to use for generalised anxiety disorder. But there are some studies that show some evidence looking at the literature and in my experience I tend to use smaller doses of it. The sedating piece we're talking about with Pregabalin is nothing compared to the sedation people can have with Quetiapine. And you know, looking at the literature, it seems to be more at lower doses. So 150 mg going up to 300 does not necessarily improve things and sometimes makes it worse and less tolerable because people feel quite groggy and less sharp. A pro to it is that when people take it, they can get that anti-anxiety effect pretty early and it's used for other disorders. It has clear evidence in bipolar depression, in psychotic illness and in unipolar depression or major depressive disorder. So Quetiapine is something that's there. It's always important to remember when we're using Quetiapine regardless of the dose. We want to do all of our metabolic monitoring. So looking at people's sugars, their weight and their cholesterol and that's a key with it because we don't know what dose that starts at. But in theory people can have those side effects at any dose.

  Dr. Jordan Bawks: [00:17:39] And so, yeah, and because of those, because of those metabolic side effects and the tolerability issues, they are listed as a second line agent in many of the clinical practice guidelines, including the one that we often use here in Toronto, the Katzman Canadian clinical guidelines.

  Dr. Jared Peck: [00:17:57] Yeah. And I guess finally, possibly, you know, we said up front the most commonly used being the SSRIs and SNRIs, but other commonly used class of drugs is the benzodiazepines. People will sometimes end up on these when they're first seeing their doctor in the context of having a real spike of their anxiety and benzodiazepines do have evidence for treatment of generalised anxiety disorder, but they can be quite tricky. They're not more efficacious or better than the other classes in the long term. And in fact you can run in some into some problems with them long term. There's short acting, benzodiazepines and long-acting benzodiazepines. The short-acting ones have a greater potential for people to misuse them because they kind of really switch on quickly and calm people down. But then they switch off and you can get a little bit of increase in your anxiety, similar to what I was talking about earlier with alcohol. And the long acting ones can do that as well. The challenge with benzodiazepines is that over time people's bodies get used to them and they need higher doses. And then they're having, as I said, somewhat of that what we call withdrawal or rebound anxiety. So we want to be careful. Often we use them when we're first starting on SSRI or SNRI to combat that potential activation or to help people get some benefit while we're waiting for the other medication to kick in. But we want to really watch how long we're keeping people on them. We also know about the comorbid substance use, and if people have a history of alcohol use disorder or other substance use disorder, we want to be really, really careful around prescribing benzodiazepines. And we want to know, obviously, what people's liver functions like, particularly as people are getting older, even though they. Their liver livers still functioning. You know, things change and the body composition changes. And we really want to avoid benzodiazepines. In the older population, people are at higher risk of falls and it can be quite dangerous.

  Dr. Jordan Bawks: [00:20:18] So when do you see yourself using benzodiazepines in when you're treating patients with generalised anxiety disorder?

  Dr. Jared Peck: [00:20:26] So as I mentioned, there's the situation when you're starting an SSRI or an SNRI and you're they're getting either some activation or increase in anxiety temporarily, then you might use that. Or even if they're not getting that to help tone things down. And that would be like.

  Dr. Jordan Bawks: [00:20:42] For weeks, like a month.

  Dr. Jared Peck: [00:20:45] I would say. So somewhere in the range of so weeks over those first four weeks or so. The other case would be the individual who I've really tried everything else and doesn't have a substance use disorder. And the benzodiazepine has helped. Right. So maybe a longer-acting one that they're taking once or twice a day. You know, they they do have a time and a place. You just want to be careful about how you're prescribing them. So in that individual, I can think of multiple people I've treated over time where we've tried everything and they're even either haven't tolerated it or they haven't gotten the benefit. So I think those would be the two cases up front. And then there's obviously cases where people have comorbid illnesses or things that are more severe and and you're using some of it as well.

  Dr. Bruce Fage: [00:21:41] So it sounds like benzodiazepines can be used with great caution for short periods of time with careful management. Dr. Peck, when you're starting somebody on a medication, what kind of things do you tell them about how likely it is to work or how likely they are to to experience a reduction in their symptoms?

  Dr. Jared Peck: [00:22:02] So, you know, the majority of people get benefit. I think it's about two thirds of people that will have benefits from a first try and then drops to around 40% for, you know, moving to a second drug. So I tell them that, you know, we're we're not going to make everything go away, but there's a good chance here. I also talk with them about anxiety in general. I think a really important key is that as part of prescribing medications and as health care professionals, it's not just seeing someone for, you know, five minutes and giving them a prescription. It's important that you look at those lifestyle modifications and talk about that stuff with them. And we're going to talk about CBT in a few minutes, but use some of those principles of CBT embedded in while you're on medication as well. So I usually talk about those things with people. The other challenge, obviously you tell people about side effects and we have to do, you know, provide informed consent. But people with generalised anxiety disorders worry a lot and they scan their environment looking for signs of danger. And you know, the environment that they're always in literally is their body. And so when people with generalised anxiety disorder are prescribed a medication, not all, but many people tend to scan their body. And, you know, if any of us scans our body, whether we're taking medication or not, we're going to notice things. And so people with generalised anxiety disorder are often somewhat more I don't know if the word sensitive or if there's just greater awareness of potential side effects or attribute physical sensations to the medication they're on. So sometimes it can be a challenge around starting a medication with with, you know, people with GAD. I think you can work through that by going with low doses, but still making sure that you're increasing them over time and sometimes meeting a little bit more often to provide the reassurance around it.

  Dr. Jordan Bawks: [00:24:13] Yeah, and that's a common thing that I emphasise when I'm starting medications in people who have anxiety and they have a history of saying like, Oh, you know, I have a lot of side effects to this or that medication and it's spending the time to go through the side effects and say like, you know, this is what you can expect. And so like this is if this is how you're feeling like that, that's okay. And like, we're going to work through this together, we're going to go slow and it's going to get better. And that, I think, is like something I really try and emphasise is that like often with SSRIs, I tell them just so they have that expectation that it might get worse before it gets better, you know, because I worry that someone's on a medication for four days. And you know what? This isn't working. It's actually making me worse. This medication doesn't work for me, but we know that they need to be on the medication for 4 to 6 weeks. So it's important to set that expectation kind of ahead of time that this is sort of what it's going to be like. Dr. Peck, let's not forget about tricyclic antidepressants. They're in a lot of the guidelines in the Katzman 2014 guidelines, Imipramine, second line. I know we don't get a lot of exposure to prescribing them in our current kind of like residency environment. What role do you see TCAS playing in in management of GAD?

  Dr. Jared Peck: [00:25:27] So that's a good question. I think for medical students, they should know what TCAS are. They're not going to be the first drug you use. People probably most commonly see them used at lower doses for pain or for sleep. Sometimes I think that they are underused in treatment of depression and in treatment of anxiety. They've been around for a long time. We have to be careful watching when people are at risk of overdose or if people have cardiac conditions, but that particularly Desipramine and Nortriptyline, which are better tolerated. I've used them in people and I think once you've gone through the first line treatments, if they haven't been effective, you definitely want to try those. There's the tolerability issue, but you can work around that. So I think we don't want to forget about them. They're one of the tools we have. It's not going to be the first tool that you use, but definitely something to remember about and consider.

  Dr. Jordan Bawks: [00:26:33] Okay, great. So before we move on to talk about the psychotherapies, let's just do a quick recap of what we covered in psychopharmacology for the management of Generalised Anxiety Disorder. SSRIs and SNRIs are the standard first-line therapy. They work fairly well, they're fairly well tolerated. It's a medication that you hear us talk about lots on the show over time. We've talked about Pregabalin, which is an emerging treatment for generalised. An anxiety disorder that has a different mechanism of action may work a bit quicker, but doesn't have the same evidence for depression if that comorbidity exists and also is a little bit more expensive. We talked about Qeutiapine, which is also a very commonly used agent sort of across the board for different disorders. That versatility is a strength, but it comes with metabolic side effects and also sedation. And that's why it remains sort of second line. We talked about the role of Benzodiazepines, a somewhat controversial medication that's used very commonly and sort of, you know, to be used cautiously. But they do have a place in the management of generalised anxiety disorder in terms of bringing people onto another first line therapy or in helping to manage people who have very sort of severe disorder, who haven't had a good response to other things. And of course TCAs, which people should still know about and should be used when other options have been tried. Moving on to psychotherapies, Dr. Peck, can you outline some of the psychotherapy options that have evidence in the treatment of generalised anxiety disorder? 

  Dr. Jared Peck: [00:28:13] So the psychotherapy with the most evidence is cognitive behavioural therapy or CBT. There's different protocols or different forms of CBT and there's things that fall under the umbrella of CBT, but that's where there's the greatest evidence for treatment of generalised anxiety disorder. Now, CBT or cognitive behavioural therapy is based on the cognitive model, which is just a way for us to look at the world so we can break down any situation into a few different elements, what the person is experiencing with respect to their mood state or their emotional feelings, what they're physically feeling in any situation, the thoughts or cognitions going through their mind and their behavioural response. When we're looking at all emotional disorders, it's hard for us to just change the mood, right? If we could do that, then that would be great. And I think our medication somewhat target that. And so in cognitive therapy, we or cognitive behavioural therapy, we recognise that those four different elements all interact with each other. So the way you're feeling emotionally impacts the thoughts that you have, the thoughts that you have, impact what you're feeling emotionally, both your emotions and your thoughts impact what you experience physically and what you experience physically feeds back and also impacts those two and the way you behaviourally respond. So the things you do can trigger emotional states or thoughts and also in either directions. And the thoughts can or the emotional state or physical sensation can trigger your behaviours. So there's these sort of bidirectional arrows between those four areas. And so since we can't directly target.

  Dr. Jared Peck: [00:30:14] People's moods or emotional state in cognitive behavioural therapy. What we can do is first get people to be aware of what they're feeling physically, what emotional state they're in, what thoughts they're having linked to that, and what their response is in terms of their actions. And in generalised anxiety disorder, we see some common thinking patterns in situations. People are often what we call catastrophizing. So sort of jumping ahead to some negative conclusions. And in general, people with GAD tend to overestimate the likelihood of there being a bad event or a bad outcome and underestimate their ability to cope. So if you take that belief about the world and there's sort of that filter over the way that you look at things, you can imagine that you start to see danger in places and you think you're not going to be able to handle that which leads into changes in your behaviour. So in CBT we try to get people to recognise these thoughts and then evaluate them. We don't try to convince people of anything but get them to to look from a sort of neutral perspective, look at the evidence around what they're predicting will happen or what they're thinking and see if we can, you know, remove some of that filter and gain some cognitive or thinking skills. But a really other important, important piece is then the be part of cognitive behavioural therapy, which is when we get people to try out little experiments of behaving in different ways and seeing if what they predict or they think will happen actually happens.

  Dr. Jared Peck: [00:32:09] And we know that, you know, basic learning theory teaches us about how people learn and that's through experiences and testing out your thoughts. So CBT can be help very helpful in that way. Specifically, when we look at the idea of behaviours people often have in anxiety disorders, what we would call avoidance behaviours, right? They often will stay away from doing things or sometimes it's an avoidance behaviour will be a mental avoidance. So not think about something or overthink about something, but they're often avoidance behaviours and some of their behaviours are also what we refer to as safety behaviours. So a safety behaviour would be a behaviour that makes you feel more calm and then you attribute success in a situation and success is often, you know, completing something or not feeling as anxious. You will then attribute it to that safety behaviour as opposed to yourself and it'll reinforce for the person that they have to do that safety behaviour. So that safety behaviour could be having a drink before they go to a certain place, or it could be double checking something multiple times, it could be having a person attend something with them. It could be, you know, taking one of those benzodiazepines that we talked about earlier before doing something. And so in cognitive behavioural therapy, we try to look at what the safety behaviours are and then test out acting in ways where we're slowly removing some of those safety behaviours so that people can learn that they do have the ability to cope with these situations.

  Speaker4: [00:34:00] Thanks, Dr. Peck, for that.

  Dr. Jordan Bawks: [00:34:03] Comprehensive introduction to the theory and sort of realities of cognitive behavioural therapy. It sounds to me like the main thrust of the CBT approach to GAD is to help anxious people re-evaluate the probability that a feared outcome will take place and also re-evaluate, like the consequences should it occur. So like helping them see that they can cope if the bad thing that they're worried about does in fact happen.

  Dr. Jared Peck: [00:34:35] Yeah. Yeah, that's that's at the core of it.

  Dr. Jordan Bawks: [00:34:39] All right. Easy peasy. So now everyone who's listening can go conduct CBT. So now I know that in the Katzman 2014 article, there are some other therapies that are mentioned as emerging kind of therapies for the treatment of generalised anxiety disorder. Can you just say a couple of words about those other therapies where they're at and kind of the evidence chain?

  Speaker5: [00:35:06] And so yeah, so there's, there's evidence for mindfulness based interventions.

  Dr. Jared Peck: [00:35:12] I view mindfulness as what would be called the third wave of CBT. So it takes CBT principles and is under the umbrella of cognitive behavioural therapy and a specific type but incorporates meditation acceptance Commitment Therapy Act is also sort of under that third-wave umbrella. And so those are a couple of the, the treatments that. That are more more advanced. And then there's specific protocols for GAD, something called the Laval model that comes out of Quebec. And in the UK, Anthony Wells has developed something called metacognitive therapy, which are forms of CBT.

  Dr. Jordan Bawks: [00:35:59] Is it Anthony Wells or Adrian Wells? 

  Dr. Bruce Fage: [00:36:05] Adrian, if you're listening, we're sorry.

  Dr. Jordan Bawks: [00:36:07] Come help us on the podcast.

  Dr. Bruce Fage: [00:36:09] Come explain your model. You'd be happy to have you.

  Dr. Jordan Bawks: [00:36:13] So there's these third wave, So there's like MBCT. So Mindfulness based cognitive therapy, acceptance and commitment therapy, and then some of the kind of like second generation, we're talking about third wave, second generation, very technical, but basically like just like progressions of CBT applied to generalised anxiety, which is sort of looking at the Metacognitive theory of worry and the Laval model. Is that correct? Okay. So I have from working with Dr. Peck, who is my CBT supervisor. I know that he knows a lot more about CBT for generalised anxiety disorder, but I think it's probably this is a good place to sort of cap the episode off for our basic medical audience and maybe we'll be able to bring Dr. Peck back and we can talk more about sort of advanced CBT techniques which will be targeted at residents and practitioners of CBT in a later episode. Bruce, why don't you give us a summary of everything we talked about today?

  Dr. Bruce Fage: [00:37:20] Sure. So I think it was really great to have you, Dr. Peck, and outlining a number of different treatments for generalised anxiety disorder. And I think we highlighted that there's more than simply medication that can be used to help people who are suffering from these these symptoms in particular. There's lots of different lifestyle modifications that people can try, such as exercise, reducing your caffeine intake as well as different psychotherapeutic techniques like CBT and some of the newer models that are that are emerging for the treatment of GAD.

  Dr. Jared Peck: [00:37:51] The one thing I'd add actually is that CBT everywhere can be hard for people to access, and not everyone needs to have CBT in individually or in a group. There's several really good books out there and if someone's motivated, they can learn a lot of these skills and the workbooks go through modules that are on a weekly basis and incorporate a lot of the tools. And so and people can get just as much benefit from that as they would from an individual course of therapy, because it's really about learning new ways to look at situations and to test out acting differently.

  Dr. Bruce Fage: [00:38:36] And I think that's an excellent point, particularly when we when we know that sometimes it can be really challenging to access mental health treatment.

  Dr. Jordan Bawks: [00:38:43] And I think from the Katzman article, they actually showed some evidence that Internet based CBT was non-inferior to in-person CBT. So I think that's an early field of research, but also another way potentially to increase access. Thanks everybody for tuning in to our episode. As always, we encourage, request, beg for your feedback. We are actively trying to make this the best possible educational experience for our listeners, so let us know what you like, what you don't like, episode length type of guests type of material covered. If you want Jordan to stop hosting the episodes, please let us know. We'll kick him off the team. And yeah, you can find us at our website psyched podcast.org or on Facebook. If you type in psyched podcast, we have our own page now. I think we're also on Twitter and you can find out how to reach us there.

  Dr. Jordan Bawks: [00:39:50] So thank you to the University of Toronto Psychiatry Department for providing funding that makes this show possible. A big thank you as well to all of the background staff at the PsychEd podcast, including all our residents and medical students and staff supervisors who make the show possible.

  Dr. Bruce Fage: [00:40:11] And special thanks to the Canadian Psychiatric Association, who is working to help us spread our message and increase the availability of free, open access, medical education.

  Dr. Jordan Bawks: [00:40:21] Thanks again. See you guys next time.

Episode 6: Diagnosing Generalized Anxiety Disorder with Dr. Jared Peck

• Episode 6: Diagnosing Generalized Anxiety Disorder with Dr. Jared Peck

  Bruce Fage: [00:00:13] Welcome to PsychED, the Educational Psychiatry Podcast by medical learners for medical learners. If you're returning listener, welcome back. If it's your first time, thanks for checking us out. Today's episode is on Generalised Anxiety Disorder and specifically in part one diagnosis of generalised anxiety disorder. Your host today are Dr. Jordan Bawks, a second year psychiatry resident and myself, Dr. Bruce Fage, a fourth year psychiatry resident at the University of Toronto. We are joined by Dr. Jared Peck, head of ambulatory psychiatric care at Mount Sinai Hospital and assistant professor at the University of Toronto. He's a local expert in cognitive behavioural therapy and a bike safety enthusiast. Dr. Peck was my first outpatient supervisor in PGY two. We worked together for about two months and I learned a lot from working with him. It's great to see you again and to be back at Mount Sinai. Dr. Peck, why don't you start us off by telling us a little bit about yourself?

  Dr. Jared Peck: [00:01:08] Thanks, Bruce, and thanks, Jordan, for inviting me to take part in this. It's great that you guys are doing this initiative and happy to help out. I've been working as a staff psychiatrist since 2009 here at Sinai. I enjoy the work. I see a lot of patients with anxiety, depression, as well as psychosis and bipolar disorder. But there tends to be a lot of anxiety that comes through the clinic here. And so I do a lot of my clinical work in that area. As you mentioned. I do cognitive behavioural therapy and I'm a little bit anxious myself. I don't always appear that way, but I can relate to some of what people go through with anxiety disorders. So yeah, that's a little bit about me. I can tell you a lot more about me in a non-professional context, but we'll we'll stick to that.

  Bruce Fage: [00:02:03] Well, we appreciate you being here despite your own anxiety. So thanks. And we're happy to work through that. We're going to talk a little bit about the objectives for this episode. So by the end of this episode, you should be able to diagnose and recognise the clinical features of Generalised Anxiety disorder using DSM-5 criteria and appreciate the differential diagnosis and how to conduct assessments to help inform your clinical diagnosis. Dr. Peck, knowing that we may have some non-medical listeners, can you give us a plain language summary of generalised Anxiety disorder to set the frame for today's podcast?

  Dr. Jared Peck: [00:02:40] Sure. So generalised anxiety disorder or GAD is essentially the medical term for people that are huge. Worrywarts. Many of us worry worry is not a diagnosis in and of itself, but when it starts to get in the way and cause impairment, that's generalised anxiety disorder. The key though is that it's not just worry. There's a lot of physical manifestations and we'll get, I'm sure, into the specifics of specifics of that when we go through the diagnoses. But in a plain language way, it's those folks that are just out of control worry.

  Jordan Bawks: [00:03:19] Do you find it useful for patients or when you're explaining to medical learners to differentiate between normal fear and anxiety and anxiety that becomes a clinical disorder? Like how do we draw that distinction?

  Dr. Jared Peck: [00:03:30] Yeah. So it's a good question and I think it's something that I discuss with every patient when we're making the diagnosis, particularly in the psychoeducation part. And frankly, for many of our disorders, right? Like we all have, sadness and sadness is different from depression in the same way. And sadness can be helpful sometimes. I think the big key differentiator between normal fear and anxiety and a disorder is the impact it's having on you. So all three of us have many years of education sitting around this table. We've written lots of exams over time, had presentations, things like that. And if we didn't have some level of anxiety or fear, then we might not have studied and we might not have gotten through some of those hoops that we needed to get through to get here. So and it's not just doctors, it's anyone, right? Anxiety can drive you to do things, and that can be good. However, when that anxiety is out of control or disproportionate with what lies ahead of you, then it can become a problem. And so I think that's really the key and we're jumping ahead. But when we get to the treatment aspect, one of the keys for people when they're learning different ways of thinking about their anxiety is to start to differentiate that when there's something in front of them that they're worrying about or that they're fearful about, kind of pulling back and recognising is this worry that's, quote, pathological or out of control, or is there something that I should be fearful from here? So I think it's a really key step to differentiate between, quote, normal fear and pathological normal fear.

  Jordan Bawks: [00:05:22] So what you're saying is that everybody worries. And what really makes the distinction between like a normal anxiety and a clinically relevant anxiety is kind of whether it's adaptive, flexible or useful.

  Dr. Jared Peck: [00:05:37] Yeah. And I think just one sort of other piece which we're speaking to, but to be more explicit worry is the thinking or cognitive manifestation of fear. And we're all animals that are wired to have a fear response. And people with anxiety disorders and GAD tend to have this faulty alarm system where maybe they misread a cue in their environment or overcall something and interpret it as, you know, being fear. So it sets off their fear system. And when your fear system is inappropriately or prematurely activated, that is when you start to be having pathological anxiety or an anxiety disorder.

  Jordan Bawks: [00:06:25] Like, why do you think GAD in particular is something that's important to learn about?

  Dr. Jared Peck: [00:06:32] I think for a few reasons. One is people with GAD tend to sort of suffer in silence, so to speak. I think people kind of dismiss anxiety and they just say, well, you know, you're not psychotic or you're not really depressed, but there's a lot of suffering that's going on out there. And if we don't explicitly learn about it or label it, then we could miss it. So I think we want to know to look for it. When we look at utilisation of health care resources, people with anxiety present to their family doctor a lot more often for non-anxious complaints for medical problems. Sometimes it's catastrophic misinterpretation of, you know, physical things. But for people listening to this who are not going to be psychiatrists but are medical students, it's important for them to know that whatever setting they're in, they're going to see people with anxiety and they they have a lot of comorbidity with other psychiatric illnesses as well as physical. And just from a work productivity perspective, we'll probably get into this a bit later. But they tend to miss work. They tend to endure their symptoms for many, many years without treatment. And they often end up fearful of things, so they might end up being unmarried or if they're not identified as having anxiety and it's seen as more just their irritability, it can lead to problems in relationships. So I think there's a variety of really important reasons to to know about it so that we can help ultimately treat people.

  Bruce Fage: [00:08:18] So thanks for providing that that context. Can you speak a little bit about the epidemiology of anxiety? What what does this look like from a population trend level? What kind of people get GAD and when do they tend to get it?

  Dr. Jared Peck: [00:08:32] Thanks, Bruce. That's a good and important question. It tends to affect women twice as much as it affects men. And it can the onset can be at any point, but there's a bit of a bimodal distribution, often laid out in adolescence. It can kick in, which corresponds to the, you know, kids or adolescents starting to have more responsibility. You know, if you think of junior high school or high school, your day is no longer as constructed and there's more free time and more decisions for you. So a little bit more falling on your shoulders. You can see it in early adulthood as well. Similar type of transition, but really you can also see it later on. Sometimes in older adults with the onset of a chronic physical disease, it can make them feel somewhat helpless and and trigger this. Um, the one-year prevalence tends to be about 3 to 8%, but only 30% of people, right? So that's like one third of people actually get formal psychiatric treatment. And as I mentioned earlier, people most commonly present in their family doctors and they can go go quite a long time until they're referred or even picked up as having anxiety and in the meantime are often presenting with headaches or gastrointestinal illness or quote, a lot of muscle tension, which can can lead to other physical issues that they present with.

  Jordan Bawks: [00:10:16] So this is a shout out to all you medical students listening. No matter what field you end up in, your goal is to do better than that 30%. All right. So after these two episodes, you're going to be able to pick up GAD and you're going to be able to at least think about or refer for the appropriate treatments. Now, my understanding of generalised anxiety disorder is that it's generally considered to be like a chronic illness. It's not something that's kind of episodic. It's like you have GAD and without treatment it's probably something that's going to be with you lifelong. Is that a is that an accurate understanding?

  Dr. Jared Peck: [00:10:56] So to some degree, yes. So, you know, major recurrent, major depressive disorder, we tend to see people going along doing reasonably well. And then they have these triggered drops. People with GAD have this chronic worry. But we do see these flares like people will cope reasonably or manage with their anxiety, but then something might happen that triggers an intensification. So it's not that it's static in that it's always there at the same level, but I would say it's more chronic just with intensification, which is unfortunately well, fortunately or unfortunately the opportunity for us to intervene, that's when they tend to get referred.

  Bruce Fage: [00:11:46] Now, I know that some people listening to this podcast right now might be worrying, Oh, I think this is me. I've been a worrier all my life, so we're going to take a step back and provide you some relief by talking about how we diagnose generalised anxiety disorder from a DSM-5 diagnostic criteria and how it technically and clinically differentiates from normal worry. So as for the DSM-5 a diagnostic criteria, the essential characteristics of GAD are sustained and excessive anxiety and worry, accompanied by either tension or restlessness occurring more days than not, for at least the last six months in a number of different areas, meaning work, school, health, finances. Et cetera. The worry is difficult to control and it is associated with at least three of the following six symptoms restlessness, feeling keyed up or on edge, being easily fatigued, having difficulty concentrating, or finding that your mind goes blank, having irritability, muscle tension or sleep disturbances. Of course, as with most DSM five diagnoses, there are some caveats in that the worry has to cause some sort of functional impairment and is not related to the effects of a medication, an illicit substance or another medical condition.

  Jordan Bawks: [00:13:06] Okay, so that's generalised anxiety disorder. Why don't we go through that kind of one more time, slightly different language, see if that sticks, because I don't know about you guys, but I find the DSM-5 criteria a lot to absorb in one pass. So basically the core of GAD is that there's this kind of like regular obsessive worry or anxiety. It's there a more days than not. It's been there for at least six months. And this is kind of what differentiates it from other anxiety disorders, but it's kind of generalised. So it's not like I'm specifically worried about dogs every day for six months. It's like, you know, the worry could be around, Am I going to make the bus? Am I going to get fired from my job? Am I do I have a problem with my knee that I need to go to the doctor? So there's kind of this general picture of it and then the worry is difficult to control. I mean, if anyone from the DSM-5 is listening, you know, don't take this the wrong way, but I've always found this a kind of a silly criteria. It's like naturally the worry is hard to control. It's been there for six months and it's interfering with their function. But and then the other the key part of the diagnosis is that there's associated cognitive or physical symptoms. So there's like the irritability. When I think of the cognitive type of symptoms, I think of the the irritability, I think of the difficulty concentrating or the mind. Going blank. And then when I think of kind of the more physical stuff, I think about the restlessness, that kind of physical agitation, inability to relax the the muscle tension, the sleep disturbance, the being easily fatigued.

  Bruce Fage: [00:14:46] So, Dr. Peck, in your clinical experience, does this resonate with the kind of patients that you see? Do you pick up a lot of these symptoms?

  Dr. Jared Peck: [00:14:57] Yeah, definitely. There's  a lot of people we have to be careful because some people label, quote, worrying in a way that they are worrying and thinking about things, but it doesn't necessarily fit into this, which gets into exactly how we tease out what they mean by worry. But it definitely resonates with a lot of folks that I see.

  Jordan Bawks: [00:15:23] Now, medical students are always looking for nifty acronyms. What do you guys use to remember the six physical symptoms, that cognitive and physical symptoms? Do you guys have one?

  Dr. Jared Peck: [00:15:33] I've never I'm not a huge acronym person. There were a couple of them that I had in med school, but I'm sorry. I can't help you out there.

  Jordan Bawks: [00:15:42] Dr. Fage, do you ever?

  Bruce Fage: [00:15:43] I find that when you're doing a diagnostic interview, some of the symptoms are similar to what you might see in a major depressive disorder. So you've covered a few of them if you've asked questions about that. So I always just try to remember the muscle tension piece.

  Jordan Bawks: [00:15:58] As like a differentiating one.

  Bruce Fage: [00:15:59] From when to not forget when you're going through a diagnostic screen.

  Jordan Bawks: [00:16:03] Yeah. For those who do like acronyms and I'm kind of a visual guy, so I like to see it spelled out on my page is I'll use TRY ICE. So that's tension, restlessness, insomnia, and then the ice being irritability, concentration, energy. But, you know, it's whatever you need to do to remember them. And if you're a genius like Dr. Park, you can just pull them out from your mind at will. You don't need any acronyms. So, Dr. Peck. Next question, What is your typical screening question for GAD during a general psychiatric assessment?

  Dr. Jared Peck: [00:16:44] So I think of it in two ways, which actually might help with not an acronym, but a way of conceptualising remembering. I always think of the sort of cognitive or thinking side of anxiety, which is the worry and then the physical side. And that physical side can take you into panic attacks, which we'll talk about in another point possibly, which isn't GAD versus the kind of more chronic physical stuff. But with I usually start off with an entry into the worry on the cognitive side. So it's usually a pretty simple question. So "Are you a worrier?" Right? Or "do you worry?". And then once you get a yes, you don't check the box, you then move in a little deeper around, "Well, what kinds of things do you worry about? Give me an example. Over the last day or so, what our worries have been going through your mind?" And then if you're getting positives there, then they hit that criteria.

  Bruce Fage: [00:17:47] I would agree. I think that using the non-clinical language and describing worry when you're bringing it up with patients is really helpful. And I try to ask about how much it impacts their function and if they feel that their worry is productive or unproductive as well.

  Dr. Jared Peck: [00:18:03] An interesting question that can sometimes confirm it is even asking if they worry about their worry. Right. Because that will take you to them being concerned about it and recognising that their worry is causing a problem.

  Jordan Bawks: [00:18:20] And what kinds of things would you look for on a mental status exam when you're with a patient that may kind of direct you into the feeling strongly that there's a generalised anxiety component, or what might you typically see?

  Dr. Jared Peck: [00:18:37] Well, so starting off with the appearance, not always, but you'll sometimes have someone who's actually got a little bit of pressured speech, not in a manic sense, but in a sort of anxious sense and sometimes can be a bit overinclusive like wanting to tell you everything, get everything in quickly. They people can be a bit fidgety or, you know, just have that sort of frightened appearance. Sometimes physically, they're not fully curled up in a ball, but you can see that they're nervous, which often settles as you're talking with them. So those are some big things and then themes that you're hearing. Right? You're going to hear the worry coming out. You'll sometimes get some reassurance seeking. They can really present sometimes as almost wanting to please you and make sure they're doing an okay job in the interview or you're just clinical interaction. So I think those are some of the common themes. Things that I see.

  Jordan Bawks: [00:19:49] Yeah. For me, that reassurance seeking, that's one to me that if I've been thinking about generalised anxiety disorder, I feel relatively comfortable about the diagnosis. And then at the end, if someone is sort of saying, well, what if, what if I get this side effect? And "What if I do this and what if that?" And when it's like things you thought they were wrapped up and then all these extra questions come up and there's this real reassurance seeking element that to me is something I usually kind of say, "Yeah, I am on the right page here". Like there is definitely an element here where the worry is really significant and I feel pretty confident about GAD.

  Bruce Fage: [00:20:28] Dr. Peck, there's some evidence that suggests that the use of standardised scales or questionnaires to help with either screening for mental illness or monitoring treatment response can improve patient outcomes. What do you think about scales in clinical practice, and are there any that you find particularly helpful?

  Dr. Jared Peck: [00:20:44] Yes. So scales I think are still underused. Measurement based care is essential in managing all of our disorders. The key is finding the right scale. So GAD-7 is a very quick seven question inventory that can be self-administered that is great for the family doctor's office. Or you could do it before seeing someone in the psychiatrist's office as well. It's fairly easy. Offhand, I don't know the numbers, but scoring it, you can see how someone's doing. You can use it to track symptoms over time. I'm pretty sure it hasn't been validated for monitoring treatment over time. There's a couple of other questionnaires that can be quite helpful. One is the Penn State Worry Questionnaire. That one really captures the cognitive element. So the worry side, and I believe it's not copyright protected so people can find that online and I find that's helpful for tracking treatment over time. Some people use the Beck anxiety inventory. My experience with it is it's more focussed on the physical symptoms. So if someone has GAD with primarily physical symptoms that worry you're going to capture more of the physical symptoms on the buy. So those are three the latter two being ones that you can use to track over time response to treatment.

  Jordan Bawks: [00:22:27] Now, keeping in mind that this is something that we plan on covering in our future episodes because we plan to do an episode on most of the major anxiety disorders, I think it's still worth talking about differential diagnosis. And, you know, I know because I've trained with you, Dr. Peck, that your approach to differentiating anxiety disorders is pretty straightforward. You want to walk us through it?

  Dr. Jared Peck: [00:22:49] Yeah. So, I mean, the person always has the answer in front of you. We know that comorbidity is the rule, so to speak. When one person has one anxiety disorder, they often have another. But determining whether they have them I think is pretty straight ahead. You can take the question, what if and have a blank that you fill in when you're thinking about what goes through the patient's mind? So if the person has panic disorder, essentially what that is, is people have had a panic attack and they're now fearful of having further panic attacks. And so their fear is, what if I have a panic attack for the person who has social anxiety disorder, the sort of core cognitive construct there that's driving their fear is the fear of being humiliated or embarrassed by others. So what if I become embarrassed or what if I'm rejected in that social situation? What if I make a fool of myself? So some version of that OCD and PTSD are technically not anxiety disorders. We used to conceptualise them that way. PTSD. It's what if I get attacked again or whatever. You know, a horrible trauma has happened to the person and OCD. What if I get these germs? What if I touch that usually related to whatever that intrusive thought is? And then we have our specific phobias, which are, you know, fairly obvious. What if the dog attacks me now, the challenging one or where people get  can slip up? Is that in generalised anxiety disorder people worry about any and everything right. So it's not just what if one thing you're going to be getting what if a whole bunch of things but what if it rains like they don't have a rain phobia. So they start to have fears of multiple different things? But I think that's a good basic way. And as I said, the person you're sitting with, if you ask the question about what they worry about, you're going to get this.

  Jordan Bawks: [00:25:12] And as you said, like one of the reasons it's hard is because the rates of co-morbidities are so high. You know, I was looking at a couple of different sources and I saw between 50 to 90% lifetime comorbidity rates and people with generalised anxiety disorder. So very well may be that they have generalised anxiety disorder and panic and or generalised anxiety disorder and depression. And let's take a second to talk about depression specifically because that's one, as Dr. Fage mentioned earlier, there's a lot of overlapping symptoms. So I find that one can be really tough to tease apart. And what's your approach to differentiating generalised anxiety disorder from depression?

  Dr. Jared Peck: [00:25:59] Well, I think it can be a challenge, especially because you're seeing people when they've entered into clinical care and as I mentioned earlier, they'll, you know, they might be a flare in their anxiety or it might not be a flare in their anxiety. It might be that this person's going along with GAD for years and then they have a depression because of this comorbidity. So when you're seeing someone and meeting them for the first time and they're depressed, they can have a major depressive episode with anxious. Distress or with panic symptoms. And so it becomes hard. So I think we want to get a really good time course so the individual, you know, might be able to tell you whether their anxiety really started in conjunction with their more recent depressive symptoms or whether it predates it. So that's one key piece, just getting that time course. And if they can't provide it, I think we underuse collateral history from family members. We want to make a plug to make sure we include family members in the care of our patients, even if it's a one-time consultation, you know, those folks around them will be able to give insights so that they can help with the time course. The other piece is, although there's this overlap, when we look at sleep, let's say people who are anxious typically have difficulty falling asleep because they just can't shut their mind down. Sometimes they wake up in the middle of the night worrying about things. People with classic depression can have that initial insomnia, but they often have that early morning awakening. Now, this isn't a complete rule, but you can often differentiate it by that. And so so that's one piece. The content of their worries is important as well because people can use that phrase worry. But what they're really doing is they're looping back on their guilt or about how they're letting people down. And it can be a lot more sort of depression or depressive cognitions. So I think that's another key.

  Bruce Fage: [00:28:24] As residents, we often work with people who struggle in some way with substance use, and it's not uncommon that a person might say to us as an explanatory model for why they use substances is that they're medicating, they're self-medicating, they're trying to cope with their anxiety by using substances. Is this something that you come across commonly in your clinical work?

  Dr. Jared Peck: [00:28:51] Yeah. So there are many people with anxiety disorders who I see who don't misuse or overuse substances, but there's definitely a subset of people who end up using their substance. Probably the two most common being people using cannabis or alcohol and looking at the alcohol. Start off with people get into just this vicious cycle because they're coming to see you. So it's probably not working out all that well. But what happens with alcohol is once the alcohol is no longer bound to the receptors, we get this rebound anxiety. So although they started off using it with one drink that takes the edge off things and probably did make them feel relaxed in a very biological way initially, it then creates a problem because their tolerance and they're drinking more and then they get these drug opposite effects with the rebound anxiety when it's out of the system. And their attempt at, quote, self-medication turns into a problem in driving their anxiety further.

  Bruce Fage: [00:30:07] So it sounds like people may use substances as a coping strategy in the short term, but in the long term, it can actually worsen their symptoms.

  Jordan Bawks: [00:30:15] Correct. This is something that we haven't been doing in our previous episodes, but it's always important to think of when you're seeing a patient in front of you who's got a mental health problem, whether there's some kind of general medical condition that's contributing to that problem. The basic blood work for someone with an anxiety disorder problem, the blood work I usually order is like a CBC, a complete blood count, thyroid stimulating hormone, vitamin B, 12. Occasionally, if someone's got like a more panicky picture, like they're talking a lot about chest palpitations, I may order like an EKG or a holter just to rule out, especially if there's a family history or something like that of a cardiac problem. Any other investigations either of you guys would do a screening basis?

  Dr. Jared Peck: [00:31:07] So I usually check their renal function as well, not because I think it's driving it, but just if we're going to be initiating medication, you kind of do that up front. I think in your typical person who you think is healthy in front of you, that's suffice. Obviously, if it's someone a little older, you might be doing extended lights or if there's worry about some other illness driving this. You always want to rule out the physical, especially since these folks can present with physical other comorbid illnesses. But you don't want to overdo it, starting to chase things there that aren't there.

  Bruce Fage: [00:31:53] Yeah, I think it's that balance, particularly if people with anxiety might be prone to wanting to investigate their medical concerns to an extent where it can become harmful. I think sometimes when I interact with family doctors, they're not really sure how aggressively to pursue somebody's complaint if they haven't found an answer. Sometimes you might consider doing liver function tests as well, because a lot of the medications, if you're going to consider a medication, a lot of them are cleared through the liver. And particularly if somebody has a comorbid alcohol use disorder.

  Jordan Bawks: [00:32:33] All right. Let's take a second to review what we've talked about for our learners and also to see if there's anything else any of us want to add. We talked about why generalised anxiety disorder is an important disorder to talk about. We talked about it's being prevalent. We talked about the common presentations to family doctors. We talked about it being undertreated. We talked about the epidemiology, the bimodal distribution, late adolescence, early adulthood, later in life. We talked about its tendency to be a chronic disorder that can have flares that precipitate presentation to treatment centres. We talked about the diagnosis using DSM-5 criteria. Six months of excessive, difficult to control, worry about a variety of different things, accompanied by at least three of six cognitive physical symptoms. We talked about differentiating generalised anxiety disorder from other anxiety disorders by the fact that it's a generalised kind of worry. And we talked about some of the common comorbidities, including depression, alcohol and other substance use disorders. Everything we talked about today sitting here now, any thoughts before we wrap up the episode? [00:33:52] Doctor Packard. Doctor Fage. [00:33:53]

  Dr. Jared Peck: [00:33:54] I think you did. You covered it all. The one thing that I think I'd add that I don't think I said earlier is people with GAD don't necessarily worry about different stuff than anyone else. So any of these worries could pass through any of our minds. It's just it's really key to focus on the hard to control part or turning off the worry as that's just a real key point there.

  Jordan Bawks: [00:34:22] So maybe not so silly as I made it out to be. We talked about the DSM-5 criteria. All right. [00:34:29] Good to put that in the humble bank for Dr. Bawks over here. Doctor Fage, any last thoughts? [00:34:35]

  Bruce Fage: [00:34:36] I mean, I think we can all appreciate that fear and anxiety are a normal part of the human experience, and it's not necessarily the intent to over pathologize somebody who might be experiencing something that's very common. But I think we've tried to elucidate the difference between that and something that actually does become problematic and causes suffering.

  Jordan Bawks: [00:34:59] Well, thanks so much for joining us today, Doctor Jared Peck. A pleasure, as always. We'll be bothering you again soon to get you back and talk about the treatment of generalised anxiety disorder. And I did see your slides on cognitive behavioural therapy for generalised anxiety disorder and I'm going to make a pitch to the group that we do a special episode on sort of advanced CBT for generalised anxiety disorder because stuff looks pretty cool. Metacognitive model. Laval Model. Anytime you've got fancy names for something, you know it's going to be good. What do you think?

  Dr. Jared Peck: [00:35:33] Well, let's see how this one turns out and how the first treatment one is and we'll go from there.

  Jordan Bawks: [00:35:39] Sounds good. Thanks so much, listeners, for joining us back at Psyched. We love to hear your feedback. Give it to us on our website. I believe we have an email address there. You can find us at psychedpodcast.org. You can also check us out on Facebook @Psyched podcast. Give us a like, give us a follow. You can stay up to date on what we're doing. You can give us feedback if you want longer episodes, if you want shorter episodes, if you want to kick the experts off the episodes, you let us know and we will think about doing it. Thanks for tuning in. We hope to have you guys back next time. This episode of Psyched was written and produced by Dr. Jordan Bawks and Dr. Bruce Fage. Our theme song is Working Solutions by Olive Music. We would especially like to thank Dr. Peck once again for making the time to help us out with the episode. This podcast and this episode was made possible by the support from the Department of Psychiatry at the University of Toronto and is produced in affiliation with the Canadian Psychiatric Association. The views expressed in this episode do not necessarily reflect those of the Canadian Psychiatric Association or the Department of Psychiatry at the University of Toronto. I'd also like to offer a big thanks to all of the board members, our staff mentors and the medical students who are affiliated with us and help us out and make these episodes possible. Take care!

Episode 5: Treatment of Schizophrenia with Dr. Andrew Lustig and Dr. Jason Joannou

• Episode 5: Treatment of Schizophrenia with Dr. Andrew Lustig and Dr. Jason Joannou

  Lucy Chen: [00:00:07] Hey there, psychEd podcast listeners. I'm Lucy Chen.

  Carrol Zhou: [00:00:10] And I'm Carrol Joe.

  Lucy Chen: [00:00:12] Today we're going to explore the complexities of recognising and diagnosing schizophrenia and hopefully simplify the content to enhance our understanding of the disorder.

  Carrol Zhou: [00:00:21] So we have a few objectives for this episode.

  Lucy Chen: [00:00:24] So first objective is knowing the diagnostic criteria of schizophrenia and specific manifestations of the disease.

  Carrol Zhou: [00:00:30] We also want to know the epidemiology, the triggers for the disease, the impact of the disease and its trajectory.

  Lucy Chen: [00:00:37] We want to know the differential diagnosis with schizophrenia and its subtypes.

  Carrol Zhou: [00:00:41] We also want to know the Mental Health Act and the legalities around forming someone with schizophrenia.

  Lucy Chen: [00:00:47] We want to know how to elicit a good history and how to approach patients with schizophrenia as well. So to help us achieve this understanding, I'm joined by two inpatient psychiatrists, Dr. Andrew Lustig and Dr. Jason Joannou, based at Chem H in Toronto. Thanks so much for taking the time to help us delve into the world of schizophrenia.

  Dr. Andrew Lustig: [00:01:05] You're welcome. Thank you for having us. All right.

  Lucy Chen: [00:01:07] So perhaps you guys can tell us a bit about yourselves and how you found yourself in the kind of work that frequently involves caring for people with schizophrenia.

  Dr. Andrew Lustig: [00:01:14] Okay. Yeah. So when I went to medical school, I did not envision a future for myself in psychiatry. I was like, really into, like the physical sciences and kind of like, I guess what they're calling a positive epistemology now. And so I, I undertook training in other specialities before psychiatry. I did some time in internal medicine and in radiology. And while those are, you know, really exciting specialities, I found the narrative to be a little thin in both of them. And no disrespect to my colleagues, of course. And the thing I found really fascinating about psychiatry is that it gives you a chance to really get to know people and to hear about their stories in like an infinite amount of detail and to talk to them about it. So I found that really exciting and that really drew me to psychiatry.

  Lucy Chen: [00:02:04] Great. Thanks.

  Dr. Jason Joannou: [00:02:06] Somewhat similar to Dr. Lustig, I was into Psych Keener. I think when you go into residency, there's the divide between the people who are born to be psychiatrists who have been working at it since they were in diapers to people who just kind of stumble across it. And definitely one of those people stumbled across it. Definitely wanted to do internal medicine. And I like the kind of reading about it, the science of learning about it. But the actual practice, I found a little mundane. And then I met a girl that's most good stories go yada, yada, yada. We're married with two kids now and she's a psychiatrist as well. But she really kind of introduced me to psychiatry, and I've been doing that since.

  Lucy Chen: [00:02:53] That's great. It's nice to get a picture of how people do this kind of work. Yeah. So let's jump into this. Diagnosing schizophrenia.

  Carrol Zhou: [00:03:02] So schizophrenia affects about one in 100 or 1% of the population. Different sources will vary, but that's something that you can quote to a patient that's easy to remember. First of all, how do we diagnose schizophrenia? Well, in order to. You need to know the five big categories of symptoms.

  Lucy Chen: [00:03:22] One.

  Carrol Zhou: [00:03:23] Delusions or fixed false beliefs about something. Two hallucinations, which are things like you're seeing or hearing or smelling that are actually not there. Three disorganised speech where, you know, basically your words are jumbled up and they don't make sense. And at the, at its worst, like kind of right now it can be called a word salad where essentially you say words that don't usually connect together and don't make any sense, four disorganised or catatonic behaviour, which includes a variety of different bizarre behaviours. Five negative symptoms, which essentially is regular human experiences that individuals with schizophrenia lack, like lack of motivation, lack of enjoyment and activities which you'll hear us talking about in a little bit. In order to diagnose someone with schizophrenia, you would need at least two of these five symptoms, and at least one of them must be either hallucinations, delusions or disorganised speech. In terms of the timeline, you need to have symptoms for at least six months. Of course, in psychiatry we always say it has to affect you socially in work, play relationships, that kind of thing, for a significant amount of time, for it to meet diagnostic criteria for a disorder, and it can't be attributable to another condition. And there are many conditions that can mimic this, as we'll talk about in a bit.

  Lucy Chen: [00:04:53] It's a severe mental illness and it affects the way patients think, process emotions, maintain relationships and make decisions. When people think of schizophrenia, they might picture Russell Crowe in A Beautiful Mind or maybe Edward Norton and Brad Pitt in Fight Club with bizarre, twisted delusions, or maybe the imagery of homeless women at Dundas Square whispering to herself and pacing in the corner. These manifestations what we call the positive symptoms of schizophrenia. So basically hallucinations and delusions. There's also a constellation of negative symptoms and cognitive symptoms that we don't typically think about. What is like someone with severe schizophrenia? Negative symptoms like what? What does that typically look like?

  Dr. Andrew Lustig: [00:05:36] Well, I guess in terms of like what they call the negative symptoms, they talk about things like alogia, which means, you know, speaking less than usual and energy of having less energy than usual and affective flattening. So essentially, for people who have negative symptoms of schizophrenia, they find it, I think, more difficult or are less likely to engage in the kind of social interaction activity that people without schizophrenia do. So, for example, they would find it more difficult to like get up at a certain time, kind of get showered, get clean, get ready for the day, prepare breakfast, pack your bags, make lunch and get out the door to get to, like, say, a job or school on time. And then if they were, say, in school, they might find it more difficult to engage with other students, to kind of actively listen and take notes and take the required complex steps to kind of succeed at the tasks that they're engaged in.

  Lucy Chen: [00:06:38] I have a question for you guys. In the context of you working in the inpatient with inpatient population and kind of seeing more extreme sort of manifestations of psychosis and schizophrenia and kind of what that looks like or maybe even like what catatonia could look like.

  Dr. Andrew Lustig: [00:06:54] Catatonia is is rare in schizophrenia now, and I've really only seen like a handful of times having seen in schizophrenia, although I understand it was pretty common like a hundred years ago. And I understand it's something of a conundrum as to why its its commonality has decreased so much. But, you know, when people are catatonic, they'll they'll either like not move at all for extended periods of time or engage in what we would regard as like purposeless movements, like holding kind of like a strange posture for hours on end or just engaging in some repetitive movement that doesn't really have an obvious function for a long period of time.

  Lucy Chen: [00:07:33] I'm thinking about also students who kind of might manifest like symptoms of poor concentration, poor memory, and I'm kind of wondering about more of the cognitive symptoms associated with schizophrenia.

  Dr. Jason Joannou: [00:07:46] So definitely, I think some of the cognitive symptoms get overlooked when we're teaching schizophrenia to medical students or even residents or even when you're doing your assessment. But they can be really impactful for the actual patients and families who have to deal with them. So some things that we do know are, you know, processing speeds, things that fancy words like Bradyphrenia just means your brain is working slower than usual. So you can actually do the task. It just requires a lot more energy and attention and it doesn't allow you to kind of like multitask as well because you're just focusing so hard on something that other people might otherwise be able to do with a lot less intent. Other things are kind of like facial recognition. So, you know, people who have suffered from schizophrenia are known to have more difficulty discerning between emotions on people's faces. So you can see how that could even play into like things like paranoia, right? If you can't read somebody's face. Right. You think they're there, have some sort of malintent or you're just not quite sure what's going on. And then your brain's already in a paranoid fashion, perhaps from your kind of positive symptoms of schizophrenia, and they kind of interplay that way. So definitely it's important to kind of think about these cognitive symptoms as well.

  Carrol Zhou: [00:09:03] When people are in an acute episode of psychosis and schizophrenia, they actually score lower on cognitive testing during the acute phase and then somehow recover after. Or after treatment?

  Dr. Andrew Lustig: [00:09:15] Yeah, definitely. Like cognitive structured cognitive testing while most often employed to detect, you know, cognitive impairment from like dementia, you know, requires, you know, focusing on a task and engaging in kind of various cognitive operations. And if somebody is, you know, either if they're disorganised or if they're distracted by by internal stimuli or if they're, say, very frightened or very distrustful, then you would expect them to score lower on a structured cognitive test for sure. Now it's recorded.

  Lucy Chen: [00:09:48] So we're only on the cusp of understanding what's going on at a neurophysiological level in schizophrenia. At this point, what we do know is that there's evidence that it is a neural developmental illness, meaning there's numerous brain anomalies and abnormalities that explain some of the manifestations of schizophrenia. By the time a patient presents with the first episode of psychosis, they already have bigger ventricles and decreased grey matter. And like Dr. Lustig was saying, they may score lower on cognitive testing because of these structural abnormalities. And in keeping with the thought that this is a neurodevelopmental disorder, children that later develop schizophrenia frequently have more social and cognitive deficits in childhood. It's also important to note that schizophrenia also tends to be associated with something called a prodromal period. So this is characterized by brief psychotic experiences and a bit of social withdrawal, and it can actually kind of appear like a depression for a few months or even years prior to the manifestation of the first episode of psychosis. So we're really getting a sense of like the heterogeneous kind of manifestations of schizophrenia and that it is quite a spectrum of presentations. And, you know, there's a clear genetic predisposition to schizophrenia and there are really triggers and neural insults that can tip a person over and and and trigger the disorder. We're commonly seeing a lot of psychosis emerging and youth with cannabis use. And we're curious about your understanding or what you can speak to about the influence of marijuana use and the risk of schizophrenia.

  Dr. Andrew Lustig: [00:11:36] Yeah, well, I mean, I think it's a somewhat controversial topic and I think the jury is still out. But as I understand it, cannabis is not thought exactly to have a causative role in the onset of schizophrenia, but that in people who have kind of a predisposition, it has a tendency to hasten the onset of the illness. And then there are these people that we see who appear to develop psychotic symptoms when they smoke cannabis for a period of time, and then they kind of like they'll come into hospital and they'll say they won't smoke cannabis, maybe they'll get some anti-psychotic medication and the psychotic symptoms will resolve and then typically they'll go back, go and go back to smoking cannabis and get the psychotic symptoms again. And oftentimes that then will kind of evolve to the point where then they have psychotic symptoms even when they're not smoking cannabis. So it seems as though that cannabis induced psychotic symptoms seem to indicate like a strong vulnerability or predisposition towards developing psychosis.

  Dr. Jason Joannou: [00:12:31] You know? Yeah. Andy's right. Like there hasn't been a formal causal link, but there never will be because you're not going to be able there's a very strong association. And this is kind of one thing, I think, with the public health policy around the legalisation of pot and, you know, various statements including the organisation that we work at, work work at, we don't work out here, there's no gym, there's no gym and they'll never be randomised controlled trial, right? So you can't say, well expose all these young people with pristine brains to pot and all these other ones without and see how many develop schizophrenia in these two groups. You're not going to get that past an ethics board or nor should you. But we have these large conscript studies from, you know, Scandinavian countries. You know, I think the ends like 18000 to 20000, and you have an odds ratio in different publications between like one and four, and it kind of converges around two of that. And there are certain risk factors whether you start smoking pot very early like before age 13, whether you're defined as a heavy user, i.e. more than 50 times in your life. And that has a very strong association with developing a primary psychotic disorder and whether those people would have had it or not, I agree with you, we will never be able to do it, but I don't think the evidence will get any stronger than it is now. And based on the fact that we can't kind of study it any closer, we're going to we can't do a randomised controlled trial in the setting.

  Carrol Zhou: [00:14:08] Yeah, there's definitely limitations to what and how you can do research around. Substance use.

  Dr. Jason Joannou: [00:14:14] And when you and when you talk to people with anything, they try to find evidence to confirm their findings versus disconfirming. And that's kind of I think is kind of human nature. Like, you know, they'll go on the Internet and they'll find things that kind of confirm what they want to believe. So what I what I tend to tell people is like there's many people, most people, in fact, who can smoke marijuana and, you know, won't become psychotic or have a psychotic experience and relatively safe in that regard. But if you're seeing me, that ain't you. And you're kind of playing with fire. And, you know, just like anyone else with any kind of substance issue or health issue, you know, if you had diabetes, you have to be careful about your sugar intake. I'm warning this is, you know, unfortunately, your brain's vulnerable for psychosis and really you should be staying away from this stuff.

  Carrol Zhou: [00:15:06] So aside from marijuana, there are several other notable risk factors for schizophrenia. For example, there's a clear genetic predisposition to developing the illness. If one pair of a monozygotic twin has schizophrenia, the other twin has a 48% chance of also developing the disease.

  Lucy Chen: [00:15:23] Interestingly, males are overrepresented in schizophrenia with a risk ratio of about 1.4 relative to females. Additionally, males tend to present earlier have poor pre morbid adjustment and have more cognitive impairments and may have a worse prognosis. Many have hypothesised that oestrogen may have a protective effect on the development of psychosis. This is further supported by the fact that women do seem to have an increased risk for psychosis after menopause. And in the Perry pardon period.

  Carrol Zhou: [00:15:57] Other risk factors for schizophrenia include immigration, urban city or growing up in a city older paternal age and having a medical problem during pregnancy.

  Lucy Chen: [00:16:08] Another reliable risk factor for schizophrenia is urban city. So living in a larger, more busier city and also older paternal age. So having a father that's older during the time of birth, having a medical problem during pregnancy or delivery is also associated with a 2 to 7 increased risk of developing schizophrenia. There are multiple things that come into play with regards to this risk, such as foetal growth retardation, intrauterine infections such as influenza, Coxsackie, B rubella, toxoplasmosis and nutritional deficiency, such as low vitamin D, placental abnormalities, RH factor incompatibility, pre-eclampsia, foetal distress and low APGAR scores. Also, if the neonate had experienced hypoxia or birth asphyxia. So these are all types of risk factors around the birth period that can play into this increased risk of schizophrenia in the context of pregnancy or delivery. I'd like to go back to this idea of like psychosis not always being schizophrenia, and that it could be the result of a mood disorder like bipolar or substance induced sort of state or a medical illness. And I'm wondering whether you guys see a lot of like medically induced episodes like psychosis that's confused the schizophrenia or other kind of manifestations of sort of psychosis that are typically seen. Yeah.

  Dr. Andrew Lustig: [00:17:38] Well, I think, again, because of the way like my practice, our practices are structured, we don't we don't see a lot of medically induced psychosis like secondary to general medical illnesses because we work at a standalone psychiatric hospital and we partner with a general medical hospital down the street where they see everyone who has medical illnesses. So that that kind of gets filtered out before people get to us. Generally in terms of, yeah, we see tons of substance induced psychosis, probably as much or more than schizophrenia. And you know, we see lots of cannabis induced psychosis because cannabis is so popular and also a lot of crystal meth induced psychosis and to some degree like like some cocaine slash kind of crack cocaine psychosis, that's pretty common as well. And then, yeah, we see psychosis secondary to mood disorders. A lot of people can't get sight either develop psychotic symptoms in the context of depression or in the context of mania. And we see a ton of that. And sometimes that can be difficult to distinguish. And then also there's this phenomenon of what they sometimes call micro psychosis, which is kind of interesting. It's when people with severe personality disorders develop some psychotic symptoms, but they don't appear to be kind of a prominent part of the clinical picture. They'll be things like visual disturbances in the like the visual periphery sometimes like like a vague kind of murmuring or someone like saying your name over and over again and things of that nature. And so that's something that we sort of like take care to try and differentiate from like a primary psychotic illness. And sometimes it's very obvious and sometimes it's like next to impossible to tease them apart.

  Carrol Zhou: [00:19:18] So another clinical pearl here, a really common differential diagnosis, a substance induced psychosis. Common substances that can cause psychosis include stimulants and hallucinogens such as MDMA, cocaine, ketamine, marijuana and mushrooms. Alcohol and benzodiazepine also cause psychosis, but it's less frequent.

  Lucy Chen: [00:19:42] Other differential diagnoses of schizophrenia include the following bipolar disorder, depression, schizotypal personality disorder, and schizoaffective disorder. These are all things that could look like psychosis or and, well, basically have psychotic components to them that look like schizophrenia. The timing and predominant symptoms of these conditions differ from schizophrenia. So that's one way you can differentiate these disorders from schizophrenia. Bipolar and depression will predominantly have a mood component rather than psychosis. And a personality disorder would reflect a pattern of behavioural abnormalities throughout their life instead of a discrete single episode of psychosis. Schizoaffective disorder is the trickiest. It describes a disorder where there's a mood episode present concurrently for the majority of the total duration of the action of the active and residual proportions of the psychotic illness, but also have a period of at least two weeks where there are just positive psychotic symptoms and no mood changes. This diagnosis can only be made after serial clinical assessments and observation of the patients, sometimes for years. So it's always on the differential. When we first meet a patient and bipolar disorder and depression, you'll predominantly have a mood component rather than psychosis and a personality disorder like a schizotypal of personality. You'll essentially have an odd pattern of behaviour throughout your entire life rather than a discrete episode of psychosis. In schizoaffective disorder, you'll essentially have mood symptoms like mania or depression, and you'll also have psychotic symptoms. But there's going to be a period of at least two weeks where there's just psychotic symptoms and no mood symptoms at all.

  Dr. Jason Joannou: [00:21:32] Yeah, I think it's the nice thing about being a general psychiatrist is that we see all things. So not every you know, if all you have is a hammer, everything is a nail, right? So sometimes that's sometimes what you risk when you go to subject. Again, not our colleagues in subspecialties who only like see first episode psychosis, who or who only see 22 Q 11 deletion syndromes. You know the very good what they do and they're great clinically. But one of the advantages of being a general psychiatrist is that you see so much of everything that when something doesn't fit the bill, it makes you question and then you kind of look into it. And, you know, there's been many times that somebody has come to me with a diagnosis of schizophrenia, and then something just wasn't right about it. Either, you know, the onsets or the or the actual, like nature of the symptoms or there was something else going on and turned out they didn't have schizophrenia. Yeah. Yeah. So it's always it's always important to revisit the diagnosis, even if it's been established before they come to you. Although I would say for schizophrenia in general, it's a pretty it's not one of those diagnoses that there's, it's pretty consistent amongst providers, unlike things like bipolar or bipolar two.

  Dr. Andrew Lustig: [00:22:50] Although, you know, I have seen people that were just like, you know, say like very odd and they had a diagnosis of schizophrenia and they were kind of like passed around and it gets written in your chart and then it gets copied every single time you get readmitted. And every discharge summary has schizophrenia written on it, then it's in your chart like 30 times. And so as a clinician, you're reading through somebody's chart and you see schizophrenia all over the place and you walk into the interview thinking, Yeah, this person has schizophrenia, but then sometimes it's helpful to, to kind of just like revisit like what are the psychotic symptoms here? Are there positive psychotic symptoms and is the diagnosis warranted or is it some something like, you know, sometimes like autism can be confused or like kind of a schizotypal of personality or something along those lines? Yeah.

  Carrol Zhou: [00:23:32] Speaking of weird and unexpected cases, what were some of the most unexpected? Sorry, What were some of the most unexpected causes of psychosis you have ever seen in your career? Thinking back.

  Dr. Jason Joannou: [00:23:47] I mean, there's a couple there's always like the weird, the weird and wacky stuff you kind of remember. So like, like when you do, like, consult liaison psychiatry, which is like when you're going to the medical wards, there's a lot of medical causes of psychiatry. So, you know, I saw some interesting, weird and wacky things like press syndrome, where people kind of whole brains like light up on MRIs and they go cortical blind and then it resolves and and stuff. So, you know, nobody thought they had acute onset schizophrenia when they were in the ICU, but they were psychotic and needed our help or what have you. But the most interesting one I had was a man, again, just revisiting who was labelled as schizophrenia treatment resistant. You know, multiple courses failed clozapine and but his symptoms just weren't proper. Like he had a he kept having visual hallucinations, which is not in not typically seen in schizophrenia more of an organic illness or kind of drug intoxication and withdrawal symptom and very articulate man. But he was profoundly suicidal because he it was tormenting him, these visual hallucinations he was having. And they weren't improving treatment. He had failed clozapine. And I just he was on a sub therapeutic dose of epival that someone added just for fun. And he had a previous history of seizures. So I was just like, Oh, well, let me just up your epival and we'll see. Maybe that will help because there were some, you know, on probing there might have been maybe this was like a partial seizure of some sort like temporal lobe epilepsy or what have you. So we just upped his up epival, didn't even, like, do anything fancy, like an EEG or whatever, and they went away and he was so thankful. Then we consulted our neurology friends. It's like, again, this is like the asystole comment. They were like, Well, the only way we'll know for sure is we take them off, see if they come back, do an EEG and.Then do it.So I proposed that to him and he said, No, thank you. I'll leave with my epival script.

  Dr. Andrew Lustig: [00:25:43] Yeah. And I you know, I actually have not seen a confirmed case, but recently read this book Brain on Fire about anti NMDA receptor encephalitis, which is I guess a weird and wonderful not wonderful if you have it cause of psychosis that can be confused with schizophrenia.

  Carrol Zhou: [00:26:04] Other medical causes of psychosis can include neurological conditions such as Lewy body dementia or dementia, with Parkinsonian features, brain tumours, seizure disorders, endocrine disorders like hypothyroidism or adrenal insufficiency, electrolytes or metabolic changes, and even lupus. Steroids, antivirals, anti-Parkinsonian drugs, digoxin antimalarials, and even carbon monoxide and heavy metals can all cause psychosis.

  Lucy Chen: [00:26:34] If you strongly suspect a medical cause of psychosis and want to do some blood work, a good place to start would be CBC. Electrolytes, including extended electrolytes, blood glucose, liver and kidney function, TSH, B 12, and imaging studies or other serum markers as indicated.

  Carrol Zhou: [00:26:56] Also always ask for collateral information from the patient's family and friends in order to find out the onset of the illness and whether there was a prodromal period of social withdrawal, bizarre beliefs or behaviour and functional deterioration. You'll find that with this patient population, the collateral information is often more reliable and very useful to your diagnosis. You probably work with some patients who have really poor insight onto their illness. They come onto your unit. They don't believe they should be there. How do you engage with someone like that?

  Dr. Jason Joannou: [00:27:29] I think the the kind of the crux of the matter is. He they don't see a reason for being on the unit and they might be distrustful anyways. And it's very important to try not to disempower them. It's a very disempowering thing to have your perhaps your civil liberties limited, to have the kind of authority of the state looming over you saying that you're ill and you need medication when you don't believe that to be true. So I think, you know, one of the most important things about doctoring is aligning with your patients. So I'll often, especially with like younger patients, I'll do things like we're all on Team Joe, we all want you to do well. And this is kind of what I've heard. This is, you know, some of the concerns that that have come up when I see this, this might imply this. So I don't I tell them what I think and why I think it and at the same time tell them that my only goal here is that I'm your doctor and I just want you to have the best health possible. And right now there might be some concerns that you don't share in terms of your safety or other people's safety while you're in the hospital, but we'll work through that together.

  Dr. Andrew Lustig: [00:28:40] Yeah, I agree. And, you know, like forming an alliance is really one of the most important things because ultimately, if you if a person really does not believe or really does not want to get treated, even despite legal measures to try and make people get treatment, it's very, very hard, verging on impossible, to get someone to have a good outcome and really kind of go with the treatment plan. So I find one thing that's helpful is to try to find I think this is what you're talking about, Jason, some kind of a common ground where even if you don't agree about the diagnosis or you don't agree about the symptoms, is there anything that you can find as common ground like you want to get back to school? This might help with that or you want to get out of the hospital or you just want to you want to get outside to have a cigarette and maybe we can work together towards that.

  Lucy Chen: [00:29:23] Other pearls specifically for interviewing a very paranoid patient, include keeping personal distance in having a respectful, curious, non judgemental attitude for really paranoid patients. We may choose not to give direct eye contact and allow as much physical space as possible for them to feel safer.

  Carrol Zhou: [00:29:44] If a thought expressed by the patient seems illogical or affectively charged in an inappropriate way, then just delve into it with curiosity. Gently guide the patient into further discussion by showing interest and asking clarifying questions so that way their defences can go down and delusional material may be more readily shared with you.

  Lucy Chen: [00:30:06] Working with this sort of population that's very, very ill. And we kind of alluded to this at the beginning, but this idea of involuntary detention and forming a patient and that process of it, how what does that process look like to put someone on a form and kind of that process of telling a patient and informing them that they're involuntarily detained?

  Dr. Andrew Lustig: [00:30:32] Yeah. So, I mean, I think it's a really tightly regulated process because, you know, as physicians in Ontario, we have a tremendous power to basically to to detain somebody who's not committed a crime, not been convicted of anything, often hasn't really done anything wrong based on something that we think might happen in the future. And so basically the way it works here is that if we think that somebody meets the threshold, you know, which is typically that they're likely to cause serious bodily harm to themselves or somebody else or suffer serious physical impairment, then essentially we have to fill out a form and then we have to give the patient a formal notice that they're being detained against their will. And typically when we give them the formal notice, which is a legal document, we also explain what's happening and answer any questions that they might have. And as you can well imagine, people are usually really, really unhappy about being detained in the hospital. The hospital's generally not a pleasant place to be. The food's not very good. People aren't that nice. There's not very much to do. And oftentimes people who are detained don't even think they need to be in the hospital in the first place.

  Dr. Jason Joannou: [00:31:47] Yeah. And then they get formal they get formal notification of their rights from somebody called a rights advisor. And they can choose to have the doctor's decision reviewed by a expert tribunal. The consent capacity board in Ontario. And that's meant to be a timely process where that occurs within a week. And then, you know, it's very difficult for patients who come into the hospital. We detain them. We say, here, here you're being detained, but here you can exercise your rights. And then all these kind of formal people are coming around and they sometimes have a hard time differentiating between the rights adviser and not being part of the hospital process or one of our colleagues. So we try our very best to kind of inform them of the rights and such. But it's, as you can imagine, not always a pleasant experience.

  Lucy Chen: [00:32:40] So just to recap, the process of involuntary admission to a hospital for a mental health reason may differ depending on the province or jurisdiction that you live in. Here in Ontario, the Ontario Mental Health Act is the law that helps lay out how it's done. The Mental Health Act outlines the criteria under which a patient is admitted voluntarily or involuntarily to certain psychiatric facilities. The hospitals with designated psychiatric facilities that can admit involuntary patients are called Schedule one facilities.

  Carrol Zhou: [00:33:17] So essentially the form one criteria require the patient you examined to have demonstrated a danger to themselves or others, and that if they continue, they will be a likely danger to themselves or others, and that this danger is likely the result of a mental disorder. So threefol. One, they have been unsafe in the past. Two, they're likely to be unsafe in the future. And three, the reason that they're being unsafe is because they suffer from a mental illness. The purpose of this form is to send this person to a schedule one facility for a psychiatric assessment.

  Lucy Chen: [00:33:57] Once the form one is completed, there's a form that you provide the patient, which is called a Form 42, which basically just lets them know that they've been put on a form one. You can actually obtain these forms. So the form one and the form 42 online by simply Googling form one, form 42, and you can actually fill them out electronically.

  Dr. Andrew Lustig: [00:34:17] I was talking to a senior colleague of mine today who's a full professor of psychiatry who told me he doesn't think he's ever correctly filled out a form one.

  Carrol Zhou: [00:34:23] Yeah. I had tried to fill out a form one, and then I ran into a staff psychiatrist who was like, Did you sign three times on the form? And I was like three times and sort of went back and realised, No, I only signed one time. So that was, that was all the questions we had.

  Lucy Chen: [00:34:41] Yeah. Sort of. Any lasting impressions you want to leave with young learners and future psychiatrists of today?

  Dr. Andrew Lustig: [00:34:53] You know, I think maybe, you know that the to be perfectly honest with you, the treatments that we have for schizophrenia right now in 2017 are poor and you know, unfortunately, schizophrenia hasn't seen the benefits that you've seen in like, say, cancer care or like cardiovascular care. And our patients, unfortunately, with actual schizophrenia, have poor outcomes. And so I think it's important to be kind of like to know that that the drug you're prescribing is probably not going to be transformative in their life and isn't going to get them back to where they want to be. And so it's important to be kind of like empathic and humane with patients and not get too caught up in, you know, like the details and the dose and the drugs and to realise that it's going to be a lifelong journey for the patient and to try to make it as, as palatable as possible.

  Dr. Jason Joannou: [00:35:47] I thought she wanted you to say something inspiring. No, no, no. For sure. And. But again, I think this is partly because we work in a very acute environment and there are many people with psychosis. I mean, we had that shared patient who I've been following for three years. And you're still shocked that he's doing so well.

  Speaker1: [00:36:13] Yeah.

  Dr. Jason Joannou: [00:36:14] And those occur. And I think those occur much more often, not where we work. So just because you found yourself to me, especially with the kind of earlier on and I think that's also why I am why we do the work we do because we I think I think there can be a lasting impact on what we do. The medications I agree with at 100%, I think they can be effective. There's just a lot of side effects associated with them as well. And especially earlier on in the in the illness, the illness tends to be much more responsive to the medications. And for people who unfortunately develop kind of more of a chronic course. And that's the same for many things like, you know, multiple sclerosis or other things. There's different kind of patterns of disease. When you when you go to read your Kaplan and Sadique and prepare for your Royal College exam, you'll learn about all these other kind of epidemiology of the disorder. They say 20% of people with schizophrenia recover completely.

  Dr. Andrew Lustig: [00:37:16] Yeah, they do say that.

  Dr. Jason Joannou: [00:37:16] The literature I mean, that's not what we see.

  Dr. Andrew Lustig: [00:37:18] Yeah, I understand that.

  Dr. Jason Joannou: [00:37:19] But yeah, no, in our particular setting. So it's important to keep that in mind. But I think you have to instil hope yet being real and honest at the same time. And that's why it's important to kind of just the psychoeducation around things like we were talking about the cannabis or kind of lifestyle or the importance of family. I say the other important, like not to minimise our treatments. Yeah, I don't know if I would say they suck. There's definitely room for improvement, but they, you know, the, the who, who's the who. Rob Ford. They did very large international studies and seventies eighties and nineties. The first one in seventies came out they were wanting to show the the promise and how great antipsychotics were and they compared outcomes in North America and UK to developing countries like India and they couldn't find a difference and they said, oh it's methodological issues, whatever, and they repeated it like the study again in the eighties couldn't find a difference and again in the nineties. So what they found was that people who are much more socially connected, more likely to be married, more likely to have a job, more likely to be part of a community when they're in these places.

  Carrol Zhou: [00:38:27] When counselling a patient, it can be helpful to conceptualize the course of schizophrenia. In thirds, approximately 20% to one third of patients will have an episode of psychosis, respond well to treatment and are able to achieve remission. About a third improve symptomatically but continue to experience relapses and about a third have a progressive and deteriorating course with residual symptoms and significant impairment.

  Lucy Chen: [00:38:55] Having an insidious onset is associated with a poor prognosis compared with presenting with a sudden and acute onset with a clear precipitating trigger.

  Carrol Zhou: [00:39:06] Poor treatment response is also associated with the male gender earlier onset of illness, poor premorbid social functioning, low premorbid IQ, negative symptoms and lack of affective symptoms.

  Lucy Chen: [00:39:20] So having a longer duration of untreated illness. So this includes the prodromal symptoms. So the time before the overt psychosis happens, having a longer duration of that is associated with a much worse prognosis. Therefore, it is also important to identify individuals as early as possible and direct them to the right resources. Ideally, a first-episode psychosis program if there's one in your area.

  Carrol Zhou: [00:39:49] Drug use and poor medication adherence are also associated with worse prognoses. Very often, an aspect of the illness involves a striking lack of insight that one is even unwell, and therefore it can be very difficult to get patients to agree to take medications and remain compliant with them.

  Dr. Jason Joannou: [00:40:10] So I think it's very important that we don't just rely on the medications that if you work with families and try to get people integrated, things like getting them into job trades, whatever school, something productive, there are people too. So not just again, not the asystole leave is broken, must fix it. They're psychotic. I must fix the psychosis and not just the psychosis. It profoundly affects the family and the people that it comes on. So, you know, again, if I don't know how to get people to do what they what I what. I Think is best for I'm such a young people, so it's hard. But like, we do what we do and I think we do good work and it doesn't always work out. But for, you know, the ones that do it does. It's very rewarding.

  Lucy Chen: [00:40:57] Thanks for being very real with us.

  Carrol Zhou: [00:40:59] Thank you so much.

  Lucy Chen: [00:41:01] And for your wisdom and pragmatic sort of contribution to our understanding.

  Carrol Zhou: [00:41:07] All right.

  Lucy Chen: [00:41:08] That's a wrap. If you record it, it's actually great.

  Carrol Zhou: [00:41:20] Yeah. Like what? Like how do they splice that in? Like, blooper? Not blooper, but, like, the real deal segments. Yeah. Keep going.

  Lucy Chen: [00:41:30] Keep. You guys are magical.

  Dr. Jason Joannou: [00:41:32] They're really good. Braised short rib.

  Dr. Andrew Lustig: [00:41:33] There. Really? That doesn't sound like Indian food to me.

  Dr. Jason Joannou: [00:41:36] You wouldn't think so, but it's actually quite delicious. Okay.

  Dr. Andrew Lustig: [00:41:39] Yeah. And that's all right.

  Dr. Jason Joannou: [00:41:41] They're also known for their gunpowder shrimp. They're quite good. Yeah. I don't know what that means.

  Lucy Chen: [00:41:47] It must be explosive. Thank you for listening to PsychEd. Please contact us on Twitter at Psyched podcast or check us out on PsychEdpodcast.org, We love hearing from you and your feedback and questions are vital to the podcast. This episode of Psyched was written and produced by DR. Lucy Chen, Carol Zhou, Phoebe Bao, Kara Dempster and June LAMB.

  Carrol Zhou: [00:42:24] Audio editing was provided by Henry Barron.

  Lucy Chen: [00:42:27] Our theme song is Working Solutions by Olive Musique. We would especially like to thank doctors Andrew Lustig and Jason Joannou for taking the time out of their schedules to share with us their expertise. This podcast was made possible by support from the Department of Psychiatry at the University of Toronto and is produced in affiliation with the Canadian Psychiatric Association. The views expressed in this episode do not necessarily reflect those of the Canadian Psychiatric Association or the Department of Psychiatry at the University of Toronto.

Episode 4: Treatment of Bipolar Disorder with Dr. Roger McIntyre

• Episode 4: Treatment of Bipolar Disorder with Dr. Roger McIntyre

  Jordan: [00:00:14] Welcome to psychEd the Educational Psychiatry Podcast for Medical Learners Biomedical Learners. We're a group of junior psychiatry residents at the University of Toronto in Canada who have come together to discuss important topics in psychiatry through our own research and with the help of our world class staff psychiatrists here in Toronto. Our topic this episode is the treatment of bipolar disorder. I'm Jordan Box, your host, and I'm joined by.

  Lucy Chen: [00:00:39] Hi, I'm Lucy Chen.

  Dr. Raben: [00:00:41] Hi, I'm Alex Raben.

  Jordan: [00:00:43] Hi, guys. Thanks for joining me today. Today, we're going to be talking about the treatment of bipolar disorder. And the expert that we have on with us is Dr. Roger McIntyre, who's a staff psychiatrist at the University Health Network in Toronto. By the end of this episode, the listener should be comfortable with information and knowledge on one the treatment of acute mania and depression in bipolar disorder, two preventing relapse in bipolar disorder through maintenance pharmacotherapy. Three. Preventing relapse through non-pharmacological interventions and for how to obtain informed consent for lithium treatment. So before I start asking questions of my co hosts, let's bring listeners up to speed on the case that we first presented in our episode three Bipolar Disorder, Recognition and Diagnosis. This is like.

  Lucy Chen: [00:01:43] So. Okay. So you're still in a merge and you've just diagnosed Devin with bipolar disorder in a current manic episode. As reminder, Devin is a 28 year old pharmaceutical rep who had just been brought to hospital by his partner Ben, because he was not sleeping, talking quickly and had become increasingly aggressive through a detailed history mental status exam and some collateral Detective work. You are confident in your diagnosis of bipolar disorder in a manic episode. Devin is waiting on a stretcher in the darkened isolation room of the Emerge department, and you need to make some decisions about how you're going to treat him and the people.

  Jordan: [00:02:28] At the front shift. So it's the moment of truth. I feel pretty confident about our diagnosis of bipolar disorder, but I guess I'm curious what my next step should be. Can one of you guys walk me through this?

  Dr. Raben: [00:02:41] Yeah, of course, Jordan. So before we jump in, we should let our listeners know that a lot of the recommendations we cover in this episode come from the 2013 canmat bipolar guidelines. These are an excellent resource and we would highly recommend looking into them outside the episode to further your knowledge. Our goal is not to repeat these guidelines, but to touch on the important points and give them some clinical context. These guidelines are Canadian, but the general principles should still be applicable for our international listeners. All right, now that that's out of the way, let's talk treatment to start in a setting like the psychiatric emergency. The first step after attending to acute safety concerns is actually clarifying the disposition. To admit or not to admit.

  Jordan: [00:03:31] Okay. So Alex so you mean, like, is this person going to come into hospital or are we going to discharge them from hospital? Yes. So how do we make that decision?

  Dr. Raben: [00:03:39] So really, there's two parts to that decision. One is whether or not there are safety concerns. And if there are safety concerns, then the patient should come into hospital. And then if there are no safety concerns, then the question becomes whether or not the patient would benefit from admission anyhow.

  Jordan: [00:03:56] I see. And when you say safety concerns, what do you mean by that?

  Dr. Raben: [00:03:59] So by this I mean imminent risk to themselves, imminent risk to others, or an imminent risk because they're not able to take care of themselves.

  Jordan: [00:04:09] I see. And by not taking care of themselves, that's just like basic needs of living, like a place to kind of keep themselves warm and safe and.

  Dr. Raben: [00:04:18] Exactly. So we'll I'll touch on it a bit with Devin and why I feel he fits into that category. So. Remember from last episode that Devin did deny any suicidal or homicidal ideation. So that rules out the first two safety concerns, especially because we corroborated that information with his partner, Ben, which you always want to make sure you do. However, Ben also explained that before Devin came to the hospital, he found him dancing in the streets without shoes, without proper fall clothes. So that prevents a risk to himself. The other piece is that he actually provoked a fight with a much larger man. So that would also present a danger to him if he were to be released from hospital. And so I think it's pretty we have pretty clear evidence in Devon's case that he's not in a good position to care for himself and that he is likely an imminent danger to himself based on that reason. Of course, you're never alone in making these kinds of distinctions, and talking to staff about your disposition is necessary and educational. Both are needed and decided.

  Speaker4: [00:05:28] I just. I don't know.

  Lucy Chen: [00:05:30] With all this in mind, you review your case with your supervisor who agrees with your provisional diagnostic assessment. And given Devin's risk and illness, together you decide to continue the form one and admit Devin to hospital.

  Speaker4: [00:05:43] Don't worry.Just because you. Okay, so that makes sense.

  Jordan: [00:05:52] Before we discuss this plan with Devon, I think we should hear from Dr. McIntyre and see what he has to say about the general approach to someone who is manic in the emergency setting.

  Lucy Chen: [00:06:03] Good afternoon, Dr. McIntyre.

  Dr. McIntyre: [00:06:05] Well, good afternoon, Carol. Nice to be with you.

  Lucy Chen: [00:06:07] Yeah. Why don't you first introduce yourself to our listeners?

  Dr. McIntyre: [00:06:11] Well, I am a psychiatrist. I'm also a professor of psychiatry and a professor of pharmacology at the University of Toronto and at the University Health Network. Among other things, I head the Mood Disorder Psychopharmacology Unit, and I'm also the executive director of the Brain and Cognition Discovery Foundation. So very pleased to be with you today.

  Lucy Chen: [00:06:29] Yeah. And it sounds like you'll provide us with many insightful answers to a lot of questions today.

  Dr. McIntyre: [00:06:35] That's my intent. I hope my deliverable meets the intent.

  Lucy Chen: [00:06:39] All right. So what are your disposition considerations when you're seeing someone who is likely manic in the emergency room?

  Dr. McIntyre: [00:06:48] In the emergency room, a person presenting with mania is the clarion call for emergency. This is an acute medical emergency. The first objective is to assure safety of that individual. And, of course, health care providers and those around this individual. The second is, is to offer relief to this individual for the incredible distress that this experience is for the person. There's a canard, a false story that unfortunately is still pervasive not only in psychiatry, but in medicine, that people like being manic. That's generally untrue. And most people do not like being mad. They find it horrifying, in fact, and they require immediate effect stabilisation. So safety first and beginning to, in fact, thinking about approaches that can offer that individual immediate symptom resolution. As is always the case in medicine, when we're in fact confronted with someone in such an acute situation, we always need to make sure that we are removing any aggravating factors to the acute manic episode, often complicated by psychosis. And we need to identify what are some of the more adaptive or some of the more therapeutic or salutary factors. For example, it's not uncommon for us in the acute setting to see people who are manic, who are taking an anti depressant medication. Well, clearly that medication must be discontinued. Is an example, very simple, axiomatic example of a aggravating factor. We also know that emergency rooms can, in fact, be very active and very busy and very stimulus prone type environments. And very often we need to create an environment that's much more settling for the individual. And that requires, in fact, obviously the appropriate infrastructure in the emergency room. But to the extent that we can control this, being cognisant of environmental factors that could be activating that particular individual. So our objectives in the acute phase are safety. Secondly, to offer immediate symptom relief through the appropriate pharmacological treatment avenues. And thirdly, to do the best that we can to engage those factors that enable acute anti manic responses and to in fact make sure we're mitigating any aggravating or provoking factors.

  Jordan: [00:09:07] All right. That makes a lot of sense. So just to summarise Dr. McIntyre's main points, first, we tend to safety and then we make sure we can reduce some of the aggravating factors by keeping the environment as calm as possible. So when a patient who is acutely manic, they might be really distractible, They're really sensitive to aggravating factors outside other people getting upset, people walking by their room, then we want to try and reduce those sort of external factors as much as we can in an emergency setting that has an isolation room, then that can be an appropriate sort of place to put someone like this to try and reduce the amount of external distractors and stimuli that are can be upsetting or provoking for them. And then next, we want to try stopping anti depressant medications as soon as possible because we know that anti depressant anti depressant medications can worsen mania. Finally, we want to offer the patient medications that may help reduce some of their symptoms. And that's something that we're going to discuss in quite a bit more detail next. So before we get into that, let's check back in with Devin. 

  [00:10:16] About finally about targets. And we have to get them today so much more.

  Lucy Chen: [00:10:24] Now that you've put together a plan with your supervisor, it's time to talk to Devin again in order to be as safe as possible. You stand just outside the door and have asked security to accompany you to Devin's room as you anticipate he might get agitated. The news of having to come into hospital. You explain to Devin your provisional diagnosis of bipolar disorder and how he was currently in a manic episode. You further explain that in order to help him, you'll be continuing the form one and admitting him to hospital. Devon shouts, I'm fine. Why are you guys trying to keep me here? Why don't you just lock me up in a jail? Devin gets up from his gurney with his hands in fists. You attempt to calm him down using a soft tone of voice to explain that you're concerned about his safety. We are quickly interrupted by more shouting. He continues to advance towards you and you realise this has become an unsafe situation that is beyond verbal de-escalation and quickly back away from the door while security moves in to confront Devin. Devin lunges for the door and is stopped by security. You call a code white. Your allied health colleagues spring into action and Devin is placed in physical restraints. You offer him oral medications to help him relax, but Devin refuses.

  Jordan: [00:11:48] Okay, let's press pause. Before we move on, I think we should point out to our listeners some of the excellent things that were done by the staff in this situation because it would be easy to skim over them. So one of the things that jumps out to me when I'm hearing about this case is when you see that Devin is getting up from the gurney with his hands in fists, there's an immediate recognition that there is a risk here, that there's a sort of an emerging violence risk based on his physical behaviour. And the immediate response is an attempt to calm him. And one of the nice things about that is using a soft tone of voice, and it's very tempting when the patient's being loud to try and be louder than them. But we know that in emergency settings that often actually escalates people. So it didn't work in this case with Devin. But using a soft tone of voices is important for that. Then when he continues to advance to wards that the staff, the staff backs out of the situation, recognising that it's continuing continually unsafe. And then there's the bringing in allied health, because you never want to be alone in these situations. And then there's also the offer of oral medications. It's tempting when someone is this upset to just go right to giving medications by needle, but it's an important act of respecting a patient's autonomy to offer them an oral medication first. So now that we've kind of gone over that a little bit, how do we approach a situation like this and what should we do next?

  Dr. Raben: [00:13:15] Yeah, Jordan, I think that's exactly the right approach. Just as you said, you want to first start with verbal de-escalation. You then want to offer oral medications and then if all else fails, you need to get the team in there to physically restrain the patient and give them IM medications for restraint. But speaking specifically about agitation in bipolar disorder, severe agitation, the CANMAT guidelines make some recommendations around this. First of all, they point out you want to start with oral medications. These include risperidone, olanzapine, or quetiapine. These are all atypical antipsychotics. If this is not an option, then you want to go to your  anti psychotics which include olanzapine, Ziprasidone OR aripiprazole. Or haloPeridol combined with lorazepam. Now. Benzodiazepines like Lorazepam, are often given alone for severe agitation in the emergency setting. But keep in mind, the CANMAT guideline suggests that for mania you should not do this. You should always combine it with an anti psychotic like Halopeidol.

  Jordan: [00:14:30] Thanks Alex, for going over the list of medications and making everything explicit. Now, Lucy, bring us back to the case and talk about what actually we would do in this scenario.

  Lucy Chen: [00:14:53] So Devon is given an anti-psychotic and a benzodiazepine. He's given IM Haloperidol, five milligrams and lorazepam, two milligrams and slowly settles and sleeps through the night. He eventually is moved to the inpatient ward where a new team takes over his care.

  Dr. Raben: [00:15:20] Okay, So I'm going to take over hosting because I know, Jordan, you did some background research on how to treat someone with mania when they're on the ward. So let's say that now you're on Devon's care team. What do we do now?

  Jordan: [00:15:35] Yeah. So the purpose of this episode is not to do a detailed review of mental health law, but it's important to cover just the basics here because based on Devon's current manic presentation, his impaired insight and judgement at this time and his inability to contract for safe behaviour, we would place Devon on a Form three and issue a Form 33 respectively. These forms are to keep Devon in hospital for up to two weeks and also to declare him incapable to make treatment decisions whereby his decisions are made by his SDM or his substitute decision maker. The nature of these forms is a matter of legislation that's based on provincial or national guidelines, and in Ontario we have special legislation for them. So you'll have to refer to your local legislation for the Local Mental Health Act that would have to do with involuntary detention and also incapacity to make decisions. In this case with Devon, his husband, Ben, would be his substitute decision maker in this scenario. Now the CANMAT guidelines break down the management of bipolar into three categories. First, the acute treatment of mania. Secondly, the acute treatment of depression. And third, maintenance treatment, which means preventing relapse of manic or depressive episodes in the future. Right now, Devon is experiencing an acute manic episode, so he needs treatment for acute mania. Here are a few things we consider in line with our general thinking about medications and psychiatric disorders.

  Jordan: [00:17:04] First off, we go with the best evidence. This is why it's nice to have something like the CANMAT guidelines available where we can look at the level one, two, three, etc. evidence for different medications because we want to use medicines with the most evidence. Number two, monotherapy when possible, or using the least medications possible to minimise possible side effects. Three, we want to match side effect profiles to patient preference when we have an option of multiple different first line agents. It can be difficult to know how to choose. So one of the ways we can choose is by asking patients what sort of side effects would be particularly troublesome for them. Because we know if we put somebody on a medicine that the side effects really bother them, they're more likely to discontinue that medicine. And lastly, we can watch for special features. And in bipolar this treating patients with bipolar disorder. This is something we think about a lot. So we look for a family history of response to an agent. For example, if there's a family history of responding to lithium, then we might be sooner to use lithium because we think that maybe this patient has some genetic or biological predisposition to responding favourably to an agent like that.

  Dr. Raben: [00:18:16] Right? Yeah, I think that's a great general approach. Jordan, You mentioned at the beginning that you go with the best evidence and you mention the CANMAT guidelines. So what does the CANMAT say about your approach to Devon?

  Jordan: [00:18:29] So CANMAT has quite a few options for a first line monotherapy for bipolar mania. Number one is lithium. Number two is Divalproex or valproic acid. Number three would be an atypical anti psychotic. Almost all of them have evidence except for lurasidone. Some of the more common ones that you probably hear or see in psychiatric settings are olanzapine, risperidone, quetiapine, and aripiprazole. And for some sort of combination of a mood stabiliser like lithium and Divalproex  and you combine that with an anti psychotic. So the algorithm in terms of choosing medications can be simplified as follows. If they are not on a first line therapy, they should be switched to a first line therapy if they are already on a first line therapy and it's not working because they're in acute mania. We should switch to a different first line therapy. So if the patient is on a classical mood stabiliser like lithium or valproic acid, then we should be they should be switched to an atypical anti psychotic or have one added or vice versa. If they're on an atypical antipsychotic and they're manic, then they should be switched to lithium or Divalproex  or have that agent added. If they fail three different first line therapies, then we got to think about going down to second line agents. And also we should be thinking about ECT,the gist of it is that it's kind of complicated and it's really nice to have a clear algorithm, which is why we'd recommend looking at the CANMAT guideline that has a really clear decision tree for how to select an agent in these scenarios.

  Dr. Raben: [00:20:09] For sure, Yeah, you should always look look that up before you do anything. And that's that's kind of a lot to take in. Jordan So but let me get try and get it straight, so. If they're coming in manic and they're already on a mood stabiliser, you would switch to an anti psychotic or add one if they are on an anti psychotic, atypical anti psychotic to begin with. You would switch to a mood stabiliser or add a mood stabiliser. And if they weren't on a first line therapy to begin with, you would initiate a first line therapy.

  Jordan: [00:20:40] Yeah, I mean, the gist of it is that we want to put people on an agent with the best evidence. So that means trying to get them on some sort of first line therapy and sometimes a combination thereof. And all this sort of talk of switching or adding basically just means that if somebody comes in and they're manic and they're on an agent, it means that they have sort of failed that agent or they have had symptoms despite being on that agent. So that means that we need to sort of do something about that, which means either switching or adding something on.

  Lucy Chen: [00:21:10] So just to emphasize, I mean, when you say failed therapy, what does that exactly mean?

  Jordan: [00:21:16] Yeah. So when we talk about medication failure, usually we mean that somebody has symptoms despite being on a therapy. But I think what you're getting at is that we need to be careful not to jump to the conclusion that a medication is not of some benefit to a patient. So when somebody is having symptoms despite being on a medicine, the first question we always have to ask is, is the person taking this medication as we prescribed it? And we know that medications are actually quite hard for patients to take, especially if they have complicated dosing regimens, which many of the mood stabilisers do. So we absolutely do need to ask people how compliant or how often they've been taking their medicine and if they've been missing doses and stuff like that makes sense.

  Dr. Raben: [00:22:01] And so assuming they're taking it and they've failed a number of medications, then just like with depression, we're we're heading down the path towards ECT or more experimental treatments.

  Jordan: [00:22:13] Yeah, exactly. And we asked our expert, Dr. McIntyre, to elaborate on this. Let's hear what he had to say.

  Dr. McIntyre: [00:22:20] Well, electroconvulsive therapy is the most effective treatment for depression and the most effective treatment for mania. And electroconvulsive therapy is the quintessential mood stabilizing therapeutic modality. I would, in fact, consider electroconvulsive therapy in any patient who because of. The severity, but usually the duration and the resistance to existing pharmacotherapy. The person's general health is in fact being compromised. I recall vividly not 20 years ago a patient who was pregnant actually who had very severe mania and consequently was not caring for herself. And there were risks, obviously, to herself and the unborn fetus. And in that case, because of the acuity and the emergency here, ECT was chosen. In fact, it was very safe and very effective. So ECT would be a consideration of acute mania after the sequential and algorithmic failure of conventional first, second and third line treatment modalities. We also would consider ECT in a situation where the person's physical health was being jeopardized because of severe mania. And or in the case of that person, I saw where the health of the fetus was being jeopardized. And in many cases as well, what we're learning, CarRol, is that patient preference matters, and there are many patients who prefer to in fact have electroconvulsive therapy.

  Jordan: [00:23:50] Now there is some debate about whether special features such as mixed features, psychotic symptoms, or rapid cycling constitute special clinical entities requiring specific pharmacological therapies. And we asked Dr. MacIntyre for his opinion on this as well.

  Dr. McIntyre: [00:24:06] I think, in fact, the message is we need to be aware of what it is that we are treating conventional therapies like atypical antipsychotic agents. Lithium and develop Divalproex  reasonable first line agents for a patient who has mania with or without psychosis. As many of our participants would be familiar with the DSM five, which was launched in May of 2013, in fact removed mixed states as a Nosllogical entity and supplanted mixed states with a new entity known as mixed features specified. Simply put, if a patient has mania in three or more opposite polarity symptoms, that is depressive symptoms, that person would have mania with mixed features. Then what we're learning is, is that perhaps in that phenotype, mania with mixed features, atypical are the most studied and seem to be the preferred agents. Now, we said earlier, Carrol, that depressive symptoms and episodes dominate the course of bipolar illness. And very often we'll see patients who have a full-blown depressive episode have some syndrome of hypomania. Again, using the DSM language, that would be a depressive episode with mixed features. And these folks often end up in emergency settings agitated, anxious and suicidal. In those cases, we have good reasons to believe that treatments like atypical or even Lamotrigine could be a reasonable first line treatment option. Unfortunately, Lamotrigine, because of the need to start low and go very slow and titration because of cutaneous syndromes linked to that particular drug. Lamotrigine is not ideal in the acute symptom resolution phase. Nonetheless, it is a treatment we would consider in a more ambulatory outpatient setting where the acuity may not be as severe.

  Jordan: [00:26:17] As alluded to earlier, since we have so many possible agents with good efficacy for treating acute mania, one of the things that we can do is to try and use family history as a shortcut to predict response. But in Devon's case, we don't have one. So the next thing we can do is try and see if there are specific side effects that should or could be avoided based on medical comorbidity or patient preference. So with this in mind, let's return to the case of Devon. And remember that we're actually having this discussion with his substitute decision maker, Ben, who is acting as sort of a communicator of Devon's preferences, values and interests.

  Lucy Chen: [00:27:00] When discussing the side effect profiles of some of the first line agents with the SDM Ben. He admits that he's somewhat hesitant about lithium and valproic acid because of their possible liver and kidney side effects and all the blood work that it's going to require knowing that Devon doesn't like needles. He also states that physical fitness is actually quite important to Devon. With this in mind, he chooses Arirprizole as the best agent for Devon to start with, since it's less likely compared to the other atypical antipsychotics, with the exception of Ziprasidone known to cause weight gain and other metabolic side effects.

  Jordan: [00:27:37] So now the CANMAT guidelines gives many first line monotherapy options. But from clinical practice that I've been involved in, I've often seen patients on two or more drugs in the short term to try and bring a more rapid resolution of mania. So we went to our expert. We asked Dr. McIntyre about this practice. Is there an evidence base to support this? We wanted to know his opinion on early and aggressive polypharmacy in the treatment of acute mania.

  Dr. McIntyre: [00:28:06] Well, in acute mania, we do have replicated evidence indicating that the combination of a conventional mood stabilising agent such as lithium with an atypical anti psychotic agent, the two together appear to have a slightly greater overall effect. That is the reduction of manic symptom severity and possibly, Carrol, to your point, maybe hasten the onset of clinically relevant symptomatic improvement. Now, the reality is most people don't like to take more than one medication, and most clinicians would not be inclined to give more than is needed. That being said, is that in the acute manic situation, these patients are often but not always hospitalized or suddenly brought into acute care type of settings or ecosystems. I do think that the initiation of polypharmacy in such cases is not just warranted, but it's evidence-based supported. I also include Carrol, to our our comments moments ago. We can't forget that hypnotics or medications and benzodiazepines are medications, and so that counts in the polypharmacy count. What we become very concerned about, Carrol, is when patients are taking two and three antipsychotics or, as I said moments ago, taking two and three benzodiazepines. This is, in fact, simply not justified. One of the challenges that we do have is when a patient's manic episode resolves. Is there, in fact, the need to keep that person on the combination treatment? And again, the responses are it depends on each individual case. There is no prescription that is tailor-made for every individual patient, but there are guiding principles. And the guiding principles are if the patient is tolerating the treatment, well, that is the acute treatment. Well, generally speaking, with some exceptions, but generally speaking, we tend to stay the course. So that maxim, what got you well is what keeps you well, generally speaking, seems to ring true.

  Dr. Raben: [00:30:14] It's great answers like that that make our staff contributors so invaluable. There is evidence to support polypharmacy in acute mania, and that includes benzodiazepines. As long as we are using them judiciously. Now. Jordan, bring us back to Devon. The decision was made to start him on ASrirprizole

  Jordan: [00:30:34] Yeah, that's. That's right. Thankfully, in our scenario, Devon had a robust response to Arirprizole treatment, and he ended up settling at 20 milligrams taken by mouth every day. If he had not had a good response, we would be fully supported by the evidence to add a mood stabilizer like lithium or valproic acid. And let's say if he had failed multiple medications, we could have used ECT. Many people know ECT exists as a treatment for depression, but it's somewhat less commonly considered for mania and it's important to keep that in mind.

  Dr. Raben: [00:31:06] Well, that's good to know that Devin responded to Aripiprazole and also that we had other options if that didn't work out. Let's fast forward now in our scenario.

  Lucy Chen: [00:31:30] A few weeks pass and thanks to Aripiprazole, Devin is no longer manic. Ben, who has been visiting regularly, remarks that Devin is himself again. Ben and Devin are both wondering when Devin can leave the hospital. You and your supervisor both agree that discharge now seems reasonable, given how much better Devin is doing. You sit down to go over the discharge plan and take a minute to evaluate Devin's medication with the goal of maintenance therapy in mind.

  Dr. Raben: [00:31:58] So I'll give some of the background on this. So unlike in unipolar depression, where a course of treatment can in many cases be self-limited. Bipolar is always considered a chronic illness and requires long-term treatment. This does not mean that a patient will spend their entire life unwell. Patients with bipolar cycle between high, low and normal mood episodes and classically the entire episode functioning of bipolar patients is considered to be quite good. If you're interested in hearing more about this, please go back and listen to our episode three, where we go over the natural history of bipolar illness and more detail.

  Jordan: [00:32:36] Okay, so we need a maintenance phase of therapy in order to prevent the symptoms from coming back or in other word, relapse. So what are our options in Devon's case? Are they different?

  Dr. Raben: [00:32:47] The pharmacological options for maintenance therapy are very similar to those used for acute mania. The exceptions are mostly that the Doane anti psychotics, that is Ziprasodine,paliperidone,  and risperidone are not as effective. The first two cannot be used as a monotherapy and only the long acting injectable risperidone is an acceptable first line treatment. The odd one out is Acenapine, and it's also dropped from that list of maintenance therapy. Interestingly, Lamotrigine is a first line maintenance therapy, despite CANMAT making it quite clear that it is not as good at preventing manic episodes as the other drugs on the list. Dr. McIntyre helped clarify its role in treatment for us.

  Dr. McIntyre: [00:33:43] Lamotrigine is an anti depressant in bipolar and we refer to it as an anti depressant mood stabiliser. Some agents are better at mitigating from below the baseline. Others are better at mitigating from above the baseline of normal. In other words, most of the atypical antipsychotics, with a few exceptions, are what we call anti manic mood stabilisers. They have some anti depressant properties, but they're more effective in mania. Lamotrigine is more effective in depression and as you are correct in highlighting its ability to forestall and prevent manic return is less impressive for the number needed to treat perspective than would be its ability to forestall and prevent depression. So it is in fact a frequently used treatment, and it's also a treatment that patients like to take. It doesn't cause weight gain. It doesn't cause sexual dysfunction. It doesn't cause cognitive impairment. And these are three reasons patients often mentioned that they are not satisfied with other treatments. So it's well tolerated. Notwithstanding, some people may get a rash. That doesn't happen that often, but it's a well tolerated medication and it's a medication that has a fairly good effect size at mitigating and preventing the return of depression. It's important, Carrol, for folks to be aware that the gene does prevent manic return. It does have anti manic prophylactic properties, but the anti manic prophylactic properties are not as robust as the anti depressant prophylactic properties. And when the United States Food and Drug Administration approved it as a mood stabilising agent, that's exactly what their position was.

  Dr. Raben: [00:35:19] Great. So according to Dr. McIntyre, we should not be hesitant to start someone on Lamotrigine for maintenance, as it does have antiemetic properties and is generally well tolerated. Luckily, in Devon's case, the Ariprizole, all which was started for acute mania, is also a valid first line maintenance therapy, and so no changes are required from a pharmacological point of view.

  Jordan: [00:35:43] That makes sense. So we have his medications figured out. But I know, Lucy, you did some reading around sort of non-pharmacological management of bipolar. And maybe you can take a break from your narration role and tell us a little bit about the psychosocial piece of bipolar treatment.

  Lucy Chen: [00:36:00] Thanks, Jordan. So despite significant strides in pharmacotherapy, recurrence rates are really high for patients with bipolar. The average is about 40 to 60% within 1 to 2 years of an episode. So either a depressive or manic episode. Even with medication, there's a ceiling for the effectiveness of pharmacotherapy, which has prompted research into the role of environmental stressors and the corresponding role of psychosocial measures such as psychotherapy to help delay relapses, stabilise episodes and reduce the episode length. Many reviews have established the importance of the role of PSYCHOEDUCATION, bipolar illness.

  Jordan: [00:36:40] And Lucy by Psychoeducation. That's just talking to somebody about bipolar disorder.

  Lucy Chen: [00:36:47] Yeah. So basically it's talking about what a manic episode or depressive episode could look like, help kind of anticipating what those symptoms are and kind of triggers for them, including stress, including like stimulants, including sleep deprivation. So it's all of the factors that sort of entail what the what the episode would look like and how to prevent it.

  Jordan: [00:37:10] Oh, and so sort of by helping them understand what their illness looks like, maybe they can catch it at earlier phases. I imagine that bringing family members into that discussion might be useful too.

  Lucy Chen: [00:37:20] Yeah, most definitely. Dr. McIntyre elaborates on what psychoeducation really entails.

  Dr. McIntyre: [00:37:26] People, in fact, need to hear that it's a common illness. They need to hear that it is an illness that doesn't imply you can't live a healthy, happy quality of life, satisfactory life. It doesn't mean you can't have family if that's part of your life narrative. It doesn't mean you can't finish your schooling and pursue a normal career trajectory. So I think many people also come to us who have bipolar, who have a family member who's affected because this is obviously an illness which is not just heritable, but highly familial. Right. And it's quite common, Carrol, for me to meet people who have bipolar, whose mom or dad or brother had bipolar and had a devastating illness. And people are alarmed, understandably, that perhaps that's what's in store for them. And I think people also need to be educated, that there's heterogeneity in bipolar, not just in the phenotype of the illness, but in the illness trajectory and in the type of medications people, in fact, need to get better.

  Lucy Chen: [00:38:24] So in addition to telling people about their illness, we need to emphasize the importance of staying on medication and adhering to the treatment plan, and also really maintaining their sleep in order to stay well for longer periods of time. Recognizing prodromal symptoms. So basically the symptoms that precede a manic episode or depressive episode and developing a relapse prevention plan are really important parts of management. Prominent prodromal clinical features include anxiety, hypomania, anger and irritability, and disturbances in sleep and attention. Recognizing and managing these symptoms early on can prevent relapse and the dysfunctional sequelae. It's also important to explain the importance of abstaining from recreational drugs like cannabis and stimulants that can also trigger an episode.

  Dr. McIntyre: [00:39:19] Cannabis exposure in bipolar disorder. Almost all the studies are very clear results in a very negative outcome. And for those who are at risk of schizophrenia and bipolar, it may even hasten the onset of the condition younger populations. So I think the taketh away of excess alcohol, the taketh away of marijuana. Of course, illicit substances are illicit, so they shouldn't they shouldn't use them anyways. These are obvious concerns. I think in everyday clinical psychiatry, antidepressants are still being used too frequently and bipolar patients and that can in some people destabilize. And finally, what I just will mention is that there are some medications that we do give patients who have bipolar that are used for other medical purposes like steroids that could also destabilize people with bipolar.

  Jordan: [00:40:05] So there's a lot to think about. I can see why education about the disorder is so important as part of the treatment.

  Lucy Chen: [00:40:13] Yeah, you definitely need to take your time with this, with your bipolar patients.

  Jordan: [00:40:18] Good to know what other psychosocial interventions can we use outside of just educating people.

  Lucy Chen: [00:40:24] So there are actually mixed results regarding the role of some therapies like CBT in bipolar illness. It's thought that it could be helpful in both phases of illness. So I'm talking about the depressive phase and the manic phase and the depressive phase. You can often have pessimistic thoughts and negative thinking and that are overly distorted. In manic phases, people can be overly optimistic and have unrealistic expectations. So basically, CBT can work on these sorts of distortions and thinking in both of these states. However, trials have yielded inconsistent results. Cbt seems to be more effective in less severe illnesses, so less recurrent patients and less severity of illness. The effects of CBT on depressive outcomes also appear to be more robust than in mania.

  Jordan: [00:41:18] So CBT seems to be better for the depressed side of the illness and also for people who have sort of a less severe type of illness. I'm just thinking about linking some of this back to our earlier episodes on the natural history of bipolar. And, you know, I think it's then important to keep CBT on the table because we know that patients with bipolar disorder, especially type two, spend a lot of time in depressive episodes. So CBT has a role. Is there anything else, any other type of psychotherapies that we've developed that may have other use?

  Lucy Chen: [00:41:49] Yeah, definitely. There's a lot of strength in the evidence for a form of therapy called interpersonal and social rhythm therapy. It's basically an adoption of interpersonal therapy for depression and derives from the fact that bipolar is often associated with poor interpersonal functioning, really, especially during the depressive phases, when there's often disruptions in the relationships with other people. And that can elicit a lot of conflict and can trigger a manic episode or a depressive episode. Also, in bipolar, there are clear disruptions in sleep wake cycles, which can also precipitate an episode. So interpersonal and social rhythm therapy essentially strives to address these triggers for episodes. So basically conflict and relationship problems and also disturbances in sleep. It's typically initiated during the post episode period. So when patients are starting to get better, patients are instructed to track and regulate their daily routines and sleep wake cycles and identify events that could provoke changes to these routines. The results generally support the efficacy of this therapy in the sense that people who received it stayed well for longer during acute phase, during their acute phase compared to patients that just received treatment management alone.

  Dr. McIntyre: [00:43:09] It's so essential that we really communicate to patients the relevance, the importance, the therapeutic offerings of some of the psychosocial interventions. There's no question that normalization of daily rhythms is highly effective and salutary in bipolar disorder. There is a manual based psychosocial intervention referred to as interpersonal therapy, social rhythm therapy, and this is a more monualized attempt to really, I think, take a common sense approach to try and set the circadian rhythms back to normal. Having a normal daily rhythm, daily schedule because we know the keepers of the day. In other words, the events around us that remind us of what time of the day it is are highly affecting the brain and highly affecting the actual behaviour of the individual. So I do think that attention to sleep, sleep hygiene and circadian rhythms is essential. I think in fact a whole attention to a more organised day. In many cases, Carol, patients would be candidates for cognitive behavioral or mindfulness based approaches in large part because Carol, this is a chronic illness. We know we're emphasising mania and depression, but most people who have bipolar are not floridly manic or depressed. They have substance trouble, depression, they've got interpersonal affective instability, they have comorbidity, they've got cognitive problems, they've got sleep problems. Many of these types of difficulties are targets with cognitive behavioural therapy and mindfulness based approaches. Bipolar doesn't affect individuals, it affects families and in many cases we'll have either couple or family type therapeutic interventions that can be critical as well as a psychosocial intervention. Our group is particularly interested in what is the role of aerobic exercise. I think it's been emphasised in this population also in major depression and I think in fact there is plenty of evidence preclinical and clinical, convergent and convincing and highly reproducible that there could be something very beneficial beyond the generic feeling good of exercise that could in fact be very helpful. Finally, cognitive remediation. Cognitive remediation is a psychosocial intervention that targets cognitive functions, depressive symptoms and cognitive problems are the principal mediators of psychosocial impairment and workplace impairment amongst people with bipolar.

  Lucy Chen: [00:45:35] In essence, psychotherapy and lifestyle modification can serve as an effective adjunct to pharmacotherapy in relapse prevention and episode stabilization in bipolar illness. Patients that receive it can have better functional outcomes than those who just receive pharmacological care, which is the ultimate goal of management.

  Jordan: [00:45:54] Well, that's good to know. It's nice to know that we have something that we can do for patients outside of just prescribing medications. Now, Lucy, do you mind taking your role back on as narrator and bringing us up to speed on where Devon is as an outpatient?

  Lucy Chen: [00:46:08] Yeah, sure. Six months later, Devin is followed up as an outpatient, but now he's severely depressed. Your gut reaction is to start an antidepressant medication. But you remember the classic warning that antidepressants can flip patients into mania and you decide to look into this further.

  Dr. Raben: [00:46:44] Although they look the same, it's important to think of bipolar depression as a separate entity from regular or unipolar depression. Antidepressants alone are not the answer. Certain modern antidepressants can be used for the short term treatment of bipolar depression, but always in combination with a mood stabilizer. The antidepressants, which can be used, include the SSRIs. Except for paroxetine, it doesn't work. And bupropion. That's it. Older antidepressants and snri carry a clear risk for inducing mania and should not be used so unopposed.

  Jordan: [00:47:25] Antidepressants for bipolar depression are just right out. So what are we left with? What should we do to stabilise Devin's mood?

  Dr. Raben: [00:47:35] It's a good question. Interestingly, there are only three first line mono therapies for treating bipolar depression, so it's different from mania. The three that you can use are Lamotrigine lithium, which you can remember because it does everything in bipolar, and quetiapine. One way to remember these three is using the acronym LLQ, which every med student knows for also standing for left lower quadrant. So if you remember LCU, you can remember Lamotrigine lithium quetiapine. The other first line treatments involve adding the antidepressants that we already talked about the SSRIs and bupropion to boost the effects of two made to mood stabilisers which aren't effective alone as antidepressants. These are olanzapine and Divalproex or valproic acid. So for instance, one combination might be olanzapine and fluoxetine, which would be a first line combination for treating bipolar depression. Finally. Lithium again, being a jack of all trades and bipolar can be combined with antidepressants or even combine with Divalproex  and all of those would be considered first line treatments for bipolar depression.

  Jordan: [00:49:03] So, Alex, the drugs that you just mentioned, those would be suitable as monotherapy for bipolar depression, and that was lithium seroquel or quetiapine and lamotrigine. Yes, but we could also use one of the antidepressants that you mentioned earlier, like fluoxetine or Sertraline. As long as we had another mood stabilising agent on board to sort of protect from the the flip into mania.

  Dr. Raben: [00:49:34] Exactly. And then again lithium can be combined with those as well.

  Jordan: [00:49:38] Okay. So the treatments for bipolar depression are somewhat different than for mania. What does the algorithm say we should do for Devin?

  Dr. Raben: [00:49:47] So it's similar to acute mania. If the patient is not on a first line treatment, they should be switched to a first line treatment. And if they are already on a first line treatment and it's deemed as failing, they need to be switched to a different first line. However, for bipolar depression, which switch you make depends on what you started with. So it quickly becomes much too convoluted for us to discuss over the podcast. The much better advice that we can give to our audience is if you're faced with this clinical question review the CANMAT guideline, look at the algorithm they've put out for you, and that will allow you to make the right choice.

  Jordan: [00:50:36] So you're saying just go back to the guidelines.

  Dr. Raben: [00:50:39] Yeah, essentially. I mean, the principles are the same as mania. You want to make sure they're on a first line treatment, but the algorithm is a bit more convoluted for depression. And so I don't think it's going to be helpful for us to discuss the details, But simply remember to go back to CANMAT, or if you're an international listener, then whatever guideline you're just jurisdiction uses. If we go back to Devin's case, Aripiprazole is not a first line treatment any longer because we're talking about bipolar depression. So in Devon's case, you're going to need to switch him to a first line treatment. And so one of these possibilities, as we discussed, is lithium. So now let's transition to talking about that. Okay.

  Jordan: [00:51:42] So, Alex, if you don't mind, I'll take over here because I did some reading around lithium, and I think it's something that our team definitely wanted to bring into the podcast because lithium is one of the best agents that we have for bipolar disorder. It's been around the longest, so we have a lot of good evidence for the treatment and prevention of both the manic and the depressive poles. And it's got a growing reputation as an agent that also decreases incidence of self injury and suicide. It's not without its challenges, though, and every medical student and resident should be familiar with the side effects of lithium therapy. And those rotating through psychiatry should be familiar with the monitoring protocol.

  Dr. Raben: [00:52:24] So what kind of side effects do we look for then.

  Jordan: [00:52:27] So we can break it down into a couple of domains of side effects? We can think about nuisance side effects, and that would be things like weight gain, sedation or people feeling kind of cognitively dulled on lithium. Some people will develop a rash. Sometimes the rash will be acne or another skin change like that. And another common nuisance side effect is polyurea and subsequent polydipsia. So lithium stimulates increased urine production. So you're being more and the also needing to drink more to sort of compensate for that.

  Dr. Raben: [00:53:11] Right. So as you say, those are sort of the nuisance common side effects. What about the more severe side effects we need to worry about?

  Jordan: [00:53:20] Yeah, so we can think about these in three broad domains. First is we need to be concerned about lithium impact on thyroid function. We need to think about lithium's impact on heart conduction. And we can think about lithium impact on the kidneys. So that actually leads us really nicely into how we monitor lithium in patients who are taking it. So first off, we want to get an EKG at baseline and then after initiation and then yearly for monitoring hypothyroidism. We're going to want to do TSH at the beginning and then also every 6 to 12 months. We're going to also want to monitor kidney function by doing creatinine levels and creatinine clearance and checking that every six months after initiation. And also, we need to heighten our frequency of blood work if we're changing the dose.

  Dr. Raben: [00:54:24] Sure, that makes sense. Yeah. So we can think of the severe side effects almost anatomically. So the thyroid, the heart, and the kidney.

  Jordan: [00:54:33] Yeah, that's right. And then also, we shouldn't forget that if the patient is a woman, that we need to do a pregnancy test before starting lithium because there are teratogenic effects of lithium. Now, another important thing that we need to think about when using lithium therapy is in lithium toxicity. So lithium in high dosages will result in kidney damage and also can result in neurological damage. So we always counsel patients who are starting lithium on what lithium toxicity looks like and the importance of lithium toxicity and the need to come to a healthcare provider if that's happening and usually emerge. So the nice thing, though, about lithium is that we have a readily available blood test to monitor the levels and that the level of lithium, with the exception of the geriatric population, we feel very comfortable about what levels are safe for patients.

  Dr. Raben: [00:55:35] And so what levels are we looking for and when are we taking these levels?

  Jordan: [00:55:40] Okay, So we can just like other parts of managing bipolar, we break it down into acute and maintenance phases. So in an acute treatment, we aim for the blood lithium level to be in Canadian numbers between 0.8 and 1.2. And for maintenance, we're aiming for a little bit lower. Between 0.6 to 1 levels over 1.5 are concerning for toxicity. A person is at quite high risk of toxicity and over 2.5 it should be associated with severe toxicity and that would be a medical emergency. An important thing as well to remember about getting a lithium level from a patient and having it be accurate is that the level should be drawn 12 hours after the last lithium dose. Otherwise you're dealing with artificially high or low levels.

  Dr. Raben: [00:56:31] I see. And so you may use this early on while you're titrating up the dose to figure out what range you're in. And then presumably when you're making dose changes or you're not sure if someone is compliant with medication.

  Jordan: [00:56:45] Yeah, exactly. So when we're initiating somebody on lithium, we're going to be doing lithium levels very frequently to make sure that our dose is appropriate. Of course, you're going to want to be using clinical judgement here as well. So if you have a patient that's responding really well on the low end of what you think the lithium level should be, for example, somebody who's had an excellent clinical response for several weeks, but their lithium levels only 0.5, You may actually discuss with that patient staying at that level as opposed to going up further because you're giving yourself a bigger sort of cushion, protecting them from some of the toxic effects of lithium.

  Dr. Raben: [00:57:29] Sure. So just like any other drug in medicine, people have individual reactions to it. And some people may respond to a lower dose of lithium than others.

  Jordan: [00:57:38] Yeah, absolutely. And then we should also, I think, mention here that in the geriatric population, so that's individuals over the 60 age of 65, these numbers are less we can be less comfortable. So let's say we have a 75 year old come in and they look lithium toxic. There's tremor, they're slurring their words. They have a bit of nystagmus and their lithium level is 0.8. If we should still be very concerned about lithium toxicity in that case. And so in people over the age of 65, we should probably be more conservative in these numbers. And I've heard some clinicians say that in people over the age of 65, if there's somebody on lithium, their lithium is toxic until proven otherwise.

  Dr. Raben: [00:58:24] That's good to know. And thank you for providing some of the clinical aspects of lithium toxicity as well for our listeners. Or is there anything else, Jordan, we should know about lithium before we wrap up the episode?

  Jordan: [00:58:37] Yeah, with chronic therapy, patients can develop a lithium tremor. So this is like a relatively fine tremor. It's about 8 to 12 hertz. And it's noticeable most often when someone's hands are outstretched or when they're trying to do a really fine motor movement. Patients can be very self conscious about tremor and practitioners. Practitioners should know what to do to address the patient's concerns. Because if somebody is concerned about a side effect, as we mentioned earlier, they're more likely to discontinue the medication so we can help deal with lithium tremor by dividing the dose into separate daily doses. So instead of giving it all at once, we can divide it up and do it in two doses or even three doses. And we can also use beta blockers like propranolol to help reduce the tremor.

  Dr. Raben: [00:59:28] Great. Thanks.

  Jordan: [00:59:33] All right. So that concludes our episode today. I hope you guys enjoyed listening. Thanks for tuning in to the PsychEd Podcast, an educational podcast on psychiatry. If you have any questions or comments, we highly encourage you guys to reach out to us. You can find us on Twitter at Psyched Podcast. We'd love to hear from you and we'll do our best to answer any questions in future episodes. Take care. We'll see you guys next episode.

  Dr. Raben: [01:00:17] This episode of PsychEd was written and produced by DR. Lucy Chen, Bruce Fage, Alex Raben, Jordan Bawks, and Carrol Zhou. This podcast was made possible from the support of the Department of Psychiatry at the University of Toronto. We'd like to especially thank Dr. Roger McIntyre. Who took time out to share his incredible wisdom, both clinically and academically, with us in his interview.

Episode 3b: Diagnosis of Bipolar Disorder (Depression) with Dr. Ariel Shafro

• Episode 3b: Diagnosis of Bipolar Disorder (Depression) with Dr. Ariel Shafro

  Hello, listeners, this is Alex here. We just have a quick announcement before we start the episode. For those of you who are interested in meeting us or want to learn more about podcasting and psychiatry education, we will be participating in two upcoming conferences and doing a workshop there.

  The first conference is the Association for Academic Psychiatry Annual Meeting from September 6th to the 9th, 2017 in Denver, Colorado. The second is the Canadian Psychiatric Association Annual Conference. This is in Ottawa, Canada, and it runs from September 14th to the 16th.

  We hope to see you out there. All right, let's get the episode started.

  Welcome to PsychEd, the psychiatry podcast for medical learners by medical learners. In this episode, we'll explore additional aspects of diagnosing bipolar disorder. As a follow up to our 3A episode, this episode we're gonna focus mostly on bipolar depression and mixed states.

  I'm Jordan Box.

  And I'm Lou Gao.

  And we're junior residents in psychiatry at the University of Toronto in Canada. Our guest this week is Dr. Ariel Shafro, a general psychiatrist and the medical education lead at Trillium Health Partners in Mississauga.

  In the last episode, we covered bipolar disorder as a mood disorder with high and low moods, the manic presentation, assessment techniques, mental status exam, the differential diagnosis, and differentiating mania and hypomania. If you haven't listened to episode three, we would suggest that you do that first before listening to this episode, as we'll be building on those concepts. So patients with bipolar disorder are sometimes manic, sometimes depressed, and sometimes euthymic, which is a term used to describe a quote normal unquote mood.

  Is a patient with bipolar disorder more likely to be a manic, euthymic, or depressed state?

  Well, we talked about this in our last episode, but I think it's worthwhile mentioning here again. There was a 15 year follow up study looking at patients with bipolar type one and bipolar type two disorders. And they had euthymia for about half the time.

  Patients with bipolar disorder type two had a longer depressive phase at about 52% of the time. Bipolar disorder type one patients were depressed about 31% of the time. Hypomania and mania were recorded at about 10% of the time.

  And I believe the bipolar two patients spent even less time than that in hypomania. And they had almost a reciprocal amount of time spent in mixed states, which we'll explore more later.

  So although bipolar disorders, they're disorders characterized by the presence of mania and hypomania, these patients actually spend significantly more time in a depressed state. So what's the diagnostic criteria for bipolar depression?

  So actually the diagnostic criteria is fairly straightforward in that it's identical as it is to unipolar depression. So you can use your same MCG CAPS screen. You still need five of nine criteria with at least one being low mood or anhedonia.

  I'd recommend that you check out our episode on depression for more details about that. That was episode one.

  So if the criteria is the same and you diagnose it the same as a major depressive episode, what is the difference between a bipolar depression and a unipolar depression?”

  Well, the reason we make that distinction is because we believe that they are different clinical entities that respond differently to treatments and they have a different clinical course.

  Let's hear from Dr. Shafro on this idea.

  If I think about the way I came out thinking of bipolar disorder, right, was just mania and depression. That's it. And I don't know if that's common for other residents, that that's the way they see it, as nothing more than just mania and depression.

  But it seems like this great gap that you have this euphoric mania and that's bipolar, right? That's bipolar. Bipolar II is something that's diagnosed by somebody else, and it's kind of this wishy-washy sort of diagnosis with not the best predictive validity or inter-rater reliability, and either rarely make the diagnosis of bipolar II because for people to be forthcoming and just tell you about euphoric hypomania is rare, or you might explain it away and say, oh, maybe they just had really good events in their life, and that's why they're kind of a little bit hypomanic.

  Whereas now it's more about, it's a different illness. It's just a different illness from unipolar depression. And if you can see enough of it and recognize it enough, it'll make it much easier to diagnose, because again, unipolar depression, bipolar depression, completely different beasts.

  As a quick example, although antidepressants are a mainstay of treatment for major depressive disorder or unipolar depression, you generally want to avoid prescribing antidepressant monotherapy to someone who has a bipolar disorder. Or at the very least, you want to be very careful when initiating that sort of medication.

  So it's really important to screen for bipolar disorder when a depression is diagnosed.

  Yeah, exactly.

  So to do that, I guess you would start by looking for any evidence of past manic episodes that they might have had?

  Yes, and teasing out past manic episodes can often be tricky.

  So that's a lot of my bipolar assessment, which is, again, it's not just a, it's become sort of more refined over time that I ask my questions in a particular way, where I'll go from the anxiety disorder questions to mood with euphoric mania being the very, very last thing I ask about. And the reason that I ask about it, because that's when the gig is up. That's when your patient knows, oh, what are you asking about?

  Whereas if you're asking them more about the depression, and then you go into the mixed features, right, where they're having the racing thoughts, the pressured speech, the out of character behavior, the more impulsive, reckless behavior, also this sort of decreased need for sleep. I'll call it this sort of wired depression. And only after I've gone through those, we'll ask about that if they have it.

  Periods like that where instead of feeling depressed, where they either feel good or better than usual. So it's a little bit sneaky at bringing up the euphoria because as soon as you mention euphoria, often people will check out, right? They'll be like, oh no, definitely not, right?

  If I ask either of you guys, have you ever felt too good? What do you mean too good? There's no such thing as too good.

  It'll be kind of this automatic dismissal. So it'll be not uncommon even after like sometimes a few days that it's only after I've met with a patient diagnosed with bipolar, and they'll deny euphoric episodes. I was like, oh yeah, maybe a few months ago, I went to Vegas and blew $10,000 on strippers and Coke before they started the Coke.

  They already started going manic. Because I think there's something about the process of being manic that's very sort of unintuitive, not gratifying. We don't want to think of the times we felt good as being pathological, right?

  It's often difficult to sort out past manic episodes. People often endorse periods of days or weeks when they felt quote unquote good. Another technique that is sometimes used is to stack questions.

  For example, has there ever been a period for days or weeks where your mood was elevated to the point where it didn't make sense to those around you, and you were sleeping very little and still energetic, and you felt like your thought or speech were racing? This is a bit more specific for patients, and one of the few times when stacking questions in psychiatry can be helpful.

  Right. So a past history of manic or hypomanic symptoms would be consistent with a bipolar diagnosis. That would make a lot of sense.

  Yeah.

  In addition, there are features of bipolar depression that just seem to be different than unipolar depression. Although this is somewhat still a controversial area of research. When depressive episodes are analyzed, there are characteristics that are more likely to predict a future diagnosis of bipolar disorder, even when they have not had a diagnosable manic or hypomanic episode at that point.

  This is a major area of research interest in the field. And one of the reasons this is so important is because if you look at individuals with bipolar over time, there's a huge lag to many of these individuals getting diagnosed with bipolar disorder. Often they'll be diagnosed with unipolar depressions for years beforehand.

  And part of the trickiness to that is that the manic episodes tend to occur later in life. So these individuals will have had several recurrent episodes of depression before they've ever had a manic episode. Let's hear Dr. Shafro on this topic.

  For bipolar depression, we're often going to be seeing this, the atypical features, the hypersomnia, the hyperphagia, especially the carb cravings. You'll see a lot more of the seasonality. So particularly in the winter, as opposed to depression often in the fall or spring, or just not following the seasonal pattern, you'll see much more frequent and serious suicide attempts earlier on in life, earlier age of onset.

  You'll also see a lot more of the comorbidities.

  So let's try to unpack that by chunking some of these risk factors into a few categories. And for the keen listener, and you're wondering where these things came from, a seminal paper on this topic is called Diagnostic Guidelines for Bipolar Depression, a Probabilistic Approach. And that was a paper that Dr. Shafro actually referenced quite frequently in his full-length interview.

  And that paper was by Mitchell, Goodwin, Johnson, and Hirschfield. I believe it was published in the journal Bipolar Disorders in 2008. And they identified many of these key risks factors, and there are multiple studies that sort of support different elements of this.

  It's too much to go into in depth here, but we do encourage you to look at those papers that will be in our show notes later for further reading.

  So there's a way to maybe chunk some of these factors that's been identified. What's the good way to do about that?

  So this category of risk factors was created by yours truly before the show. If you guys can come up with a cool mnemonic, please write in to us, and we'll license it together and make millions. So the categories of risk factors, and keep in mind these are risk factors that are supposed to help clinicians suspect bipolar disorder in individuals without clear manic episodes and who are presenting with depressive episodes.

  Does that make sense?

  So the first category is family history. This one's pretty intuitive. The strongest risk factor here is a family history of bipolar disorder.

  That should be pretty intuitive if you're seeing a patient with a unipolar depression, strong family history of bipolar disorder. You're going to be quite suspicious that your patient has an underlying bipolar disorder themselves. The literature also speaks about being wary for a bipolar disorder when patients have a family history of a psychotic disorder, family history of completed suicide, family history of alcohol and substance use disorders.

  And sometimes it's helpful when you're asking about a family history of psychiatric disorders after you kind of asked about each family member to just go after, okay, is there anybody in the family who's been diagnosed with bipolar disorder, schizophrenia or the psychotic disorders? Is there anybody who's died from suicide? To go after these things a little bit more explicitly, sometimes that can be illuminating.

  And keep in mind that the research is mostly around first degree relatives with these disorders. So, you know, we're less concerned if there's a second cousin or a third aunt or something like that. The second category is what we've termed soft bipolar traits.

  So here you see any history of subthreshold mania. So maybe somebody had two out of seven GST paid criteria, or they had four symptoms, but only for two days. As well, if they have a depression or any history of a depression with mixed features, and we're going to talk more about mixed features later in the show, but that's been shown to indicate a strong likelihood of the patient having an underlying bipolar disorder, and the DSM actually makes a specific note of that under the mixed features criteria.

  And then there's also any history of cyclothymia, or cyclothymic features.

  So without getting into too much detail, I mean, so cyclothymic features or cyclothymic disorder is just basically this idea that sub-syndromal, so not meeting, you know, diagnostic criteria for manic or depressive episode are present for an extended period of time in someone's life. So to summarize, I think all these, the last three criteria, sub-threshold mania, depression with mixed features, cyclothymic features, just point to the fact that some degree of manic symptoms not quite meeting threshold for diagnosis for manic or hypomanic episode seem to exist at some point in the illness. And that in itself might be a risk factor for the fact that the depression you're seeing in front of you may actually be part of a bipolar disorder.

  Now, the third category that we created was sort of special features of the depressive episodes. So one thing you'll see come up quite a bit is an atypical depression. So in the DSM, this is coded as a specifier, so major depressive episode with atypical features.

  And the hallmarks of that are hypersomnia, hyperphagia and anergia. Next, psychomotor retardation has been seen as an individual risk factor. Psychotic symptoms during depression is a risk factor that a person may have underlying bipolar disorder.

  And you also see kind of elements about the episodes in terms of their chronology. So you tend to see individuals with bipolar disorder having earlier first episodes of depression in comparison to their unipolar cohorts and also more episodes and briefer episodes of depressions. As well, it's worth noting here that catatonia is something that would certainly raise your suspicion for bipolar disorder, as that's sort of the most, bipolar disorder is the most common underlying etiology of presentations of catatonia, and that's something that a lot of people often miss.

  They usually think it's associated with psychosis, for example. The last criteria or category is antidepressant response. So this comes in two, there's two important factors here.

  One, patients with bipolar depression tend to have a diminished response to typical antidepressants, so they're not as effective. Patients will often describe that as sort of like a, sometimes described by psychiatrists as like a poop out. So the medication works for a couple of weeks, maybe a month, and then it just stops working, even if it titrates up.

  And then secondly, and this is the part that's really important for clinicians to be aware of, is an increase in what's called sometimes activation syndrome. So patients feeling really wired taking like an SSRI and having increased suicidal ideation. And that would be a situation that you would want to know about right away, and you would want to help manage right away.

  And that may actually represent a spectrum of the phenomenon of switching, so to speak. The reason that you don't want patients with an underlying bipolar disorder on antidepressant monotherapy is that it increases the risk that they will have a switch where they go from a euthymic or a depressed state into a manic episode as a result.

  Yeah, that's right. That's that switch that you'll often hear supervisors or psychiatry staff talking about and everybody watches out for, understandably.

  So family history of bipolar disorder, kind of these, you know, subthreshold manic symptoms, certain features of depressive episode, and these atypical or strange responses to antidepressants. These are factors for a presentation of depression that makes it more likely that the underlying diagnosis is bipolar disorder. Now, the other thing that has come up several times is this idea of mixed features.

  What is that exactly?

  These are a lot like they sound, mood episodes that feature a mixture of symptoms from depression and mania. But let's take a second to iron out our terminology. A mixed mood episode is a bit of an older term that comes from the DSM-IV, where you could diagnose somebody with a, quote, mixed mood episode if they met full criteria for both a manic episode and a depressed episode at the same time.

  In DSM-V, it's been changed to a modifier, meaning that you can diagnose depression with mixed features or mania or hypomania with mixed features, but there's no standalone mixed episode.

  Right, so the basic phenomenon hasn't changed, the fact that patients can present with symptoms of depression and mania simultaneously. But we're just going to be focusing in on how the DSM-V conceptualizes this idea.

  So the criteria to meet mixed features is fairly straightforward. For manic or hypomanic with mixed features, it is three of the six, low mood, anedonia, second motor retardation, fatigue or loss of energy, feelings of worthlessness or guilt, and suicidal ideation or preoccupation with death.

  And this is in addition to meeting the criteria fully for a manic or hypomanic episode. And so this mixed features criteria is a little bit different than the full MCGI caps in that it omits a couple of criteria. It doesn't include appetite, sleep or changes in concentration.

  Why is that?

  Well, that's a good pick up first off. And while I didn't sit on the DSM publication committee, I bet they're thinking here is that these are three areas of overlapping symptoms, in particular concentration and sleep. These are symptoms that could be altered in either a manic state or a depressed state.

  And leaving them out makes you more sure that you are looking at a true mixed features situation, so sort of lowering your rate of false positives. So for a depressed episode with mixed features, you're looking for three out of these seven criteria. One, elevated or expansive mood.

  Two, elevated self-esteem or grandiosity. Three, more talkative or pressured speech. Four, flight of ideas or subjective experience of racing thoughts.

  Five, increased energy or goal-directed activity. Six, involvement in activities with painful consequences. Or seven, decreased need for sleep.

  So that's actually a bit more similar to the criteria for a manic episode. But again, the symptoms are slightly different. For example, irritability or irritable mood is not in the criteria.

  Neither is distractibility or agitation.

  Now, their reasoning is apparently similar to the mania with mixed features. They are trying to eliminate features that may be common to both disorders, that may artificially drive up mixed scores and give you false positives for a mixed screen. But the problem here is that many researchers of mixed states feel that this is having the bar set too high.

  In particular, the concern is that distractibility, irritability and psychomotor agitation are amongst the most common symptoms in mixed states.

  So these are the criteria for a mixed feature specifier for a manic or hypomanic or depressive episode. But I think the most important takeaway here is the fact that manic and depressive symptoms can coexist and when it reaches a certain threshold, a diagnostic specifier of with mixed features need to be considered.

  Yeah, and looping back to diagnosing bipolar depression, it also increases the likelihood of a depressive episode representing an underlying bipolar disorder rather than unipolar depression. So that's why, you know, we're thinking about these things.

  Right. So in the end, what do we do with this information?

  Actually, I would be starting with an at-depressant. And part of that is conscious because I want to be more like my peers, who will be more likely to see these patients as unipolar, that might not spend as much time going over all those sort of probabilistic risk factors for bipolar. And the fact that, again, the antidepressants in general would be more benign treatment.

  They tend to be better tolerated, at least for patients with unipolar depression. With bipolar depression, it actually tends to cause tons of side effects. While also warning them that I wonder that they could be on the spectrum of bipolar by having these mixed features.

  So making sure to give very, very clear warnings on possible mixed switching. And again, not just euphoric, but again, that mixed agitated. If they start noticing increased thoughts of suicide, I tell them to stop it immediately, stop the medication right away.

  And that's where I might be more likely than to use those treatments that have evidence for both.

  So in summary, when a patient is diagnosed with depression and you feel that they actually meet criteria for bipolar disorder, that you're convinced that they have had previous manic or hypomanic episodes, then the treatment should be the treatments that are indicated for bipolar depression. But if not, and they have some of these features for a possible diagnosis of bipolar depression, then you will still be treating them as if you would treat a unipolar depression or a major depressive disorder. But keeping in the back of the mind, depending on how many of these factors they have, that they might be at increased risk for bipolar disorder and that they may experience an atypical response to the use of antidepressants.

  And just to highlight it, those atypical responses to antidepressants are, again, inadequate response. B, activation syndrome, so where patients are feeling wired, restless, and can have increased suicidal ideation. And then C, a switch or a flip into a manic phase of illness.

  And all of these sorts of things are why you would want to keep a closer eye on a patient who you are worried about may have an underlying bipolar disorder. And to do that, you may bring them back for follow-ups more frequently or have other ways of checking in on them in between appointments to make sure they are tolerating their medication.

  So in this episode, we covered ways to diagnose bipolar disorder when the presentation is depression. Firstly, different ways of screening for past experiences of manic symptoms. And secondly, by looking for features that might be suggestive of an underlying bipolar disorder rather than a unipolar depression.

  Second, we also talked about the mixed feature specifier in that symptoms of depression and mania or hypomania can coexist at once. And lastly, we covered some differences in the management when the suspected diagnosis in depression is bipolar disorder or there's a high index of suspicion for an underlying bipolar disorder in someone who has been diagnosed with a depression.

  And to hear more about the treatment of bipolar disorder, you'll have to stay tuned to PsychEd, as I believe our episode 4, which is in production right now, covers the treatment of bipolar disorder. And hopefully we'll touch on many of the things we brought up in these last two episodes.

  Thanks for tuning in to this month's episode of Psyched, the psychiatry podcast for medical learners by medical learners. As always, we're welcoming listener feedback. One of the things you may have noticed about today's episode is that we did not have a case.

  If you felt strongly about that, either that it didn't take away from the learning or it was something that you felt was really missing, please write to let us know. We're always trying to improve our product and for our listeners. Big thanks to Dr. Ariel Shafro, who took time out of his busy schedule to come interview with us.

  And it was a pleasure personally getting to listen to his clinical pearls once again, as he was very influential in the early stages of my medical training. Big thank you to the Department of Psychiatry at the University of Toronto, who is a supporter of the podcast. Thanks to our production team who work behind the scenes, including our audio editor, Henry Barron.

  Thank you to the members of the Psyched team that put together this podcast, including Lou Gao and Alex Rabin and Teresa. Acknowledgement to Olive Musique, who produced the soundtrack that you hear on this episode. So if you like our stuff, please come find us on Twitter at PsychedPodcast.

  Find us at our website, psychedpodcast.org, or you can fire us a direct email at info at psychedpodcast.com. Looking forward to having you guys back in the future. Take care.

Episode 3a: The Diagnosis of Bipolar Disorder (Mania) with Dr. Mark Sinyor

• Episode 3a: The Diagnosis of Bipolar Disorder (Mania) with Dr. Mark Sinyor

  Luke: [00:00:00] And so you're an emerge. Your next patient is Devin, a 28 year old pharmaceutical rep. He was brought in after running through his office earlier in the day shouting, I am king of the world. His partner, Ben, says that Devon is not acting like himself and hasn't slept in three nights and isn't making any sense. In his room, Devon has ripped off his shirt and is repeating, I am Jesus, I am your king.

  Jordan: [00:00:27] What do you do next?

   Luke: [00:00:33] It's rolling now. Perfect. Welcome to psychEd the Educational Psychiatry Podcast for Medical learners by medical learners. I'm Luke out and I'm here with Jordan Box. We are both junior residents at University of Toronto. And today we'll be talking about mania and bipolar disorder. We're joined today by Dr. Mark Sinyor, who is an associate scientist and staff psychiatrist at Sunnybrook Health Science Centre.

  Dr. Mark Sinyor: [00:00:58] So thanks for having me. Yep. So I'm a psychiatrist here at Sunnybrook. I do mood and anxiety disorders, mainly outpatient work, and I have an interest in my main research areas in suicide looking either at suicide epidemiology. And we're also doing some some clinical trials. But I also have some interest in some other things like the placebo effect and randomised control trial design.

   Luke: [00:01:21] So today we'll talk about the basics of bipolar disorder with a focus on mania and the manic presentation. Jordan, tell us a little bit about just how bipolar disorder affects the world.

  Jordan: [00:01:34] Yeah. So whenever we think about mental health disorders, we want to think about how prevalent they are and how often we see them. And that helps us to get a feel for when to watch out for them. So bipolar disorder affects more than 1% of the world's population, irrespective of nationality, ethnic origin or socioeconomic status. And one of the interesting and difficult things about bipolar disorder is that it tends to occur in young adulthood, and that means that it can lead to profound impact on early career and family development.

   Luke: [00:02:07] So it kind of in plain English, like what is bipolar disorder?

  Jordan: [00:02:13] Bipolar like depression is a mood disorder, meaning it's a mental health disturbance characterised by prolonged, intense, pathologic emotional states. So it's normal to feel happy or sad in response to a life event, say fantastic test mark, or the loss of an important person in your life or the loss of a job.

   Luke: [00:02:35] Right? So what makes something pathologic?

  Jordan: [00:02:38] Well, it's that the reaction almost takes on a life of its own. So it persists over days and weeks. It's a little bit less reactive to life events and associated with other specific cognitive and behavioural symptoms.

   Luke: [00:02:52] So so like in depression, which we already talked about, it was like a sense that the person is feeling sad no matter what was happening around them beyond just responding to life stress.

  Jordan: [00:03:03] Mm hmm. Yeah. And in depression, too, it's not just the mood that you're feeling sad, but it's you're almost unable to to become happy, right? That that that serves as that sort of differentiating mark. And we see the same thing in manic episodes, which we're going to talk about, where people have this really intense mood state that seems to be going on irrespective of what's going on around the person.

   Luke: [00:03:26] So so you mention this thing called mania manic episodes. What is that?

  Jordan: [00:03:33] The meaning in plain English. Why don't we let Dr. Sinyor take a stab at that?

  Dr. Mark Sinyor: [00:03:37] Oh, okay. Uh, a manic episode is an episode lasting for at least four days where someone has an intense change in their mood. So either euphoria or irritability, accompanied by a number of other symptoms, almost always with a decreased need for sleep. And a key component of that is not just not needing sleep, but also not feeling tired. So if you're interviewing somebody and they say, Yeah, I had a lot less sleep, but then I was exhausted the next day, that would be quite unusual in mania, and it's typically accompanied with a number of other symptoms, things like an increased rate of speech, increased rate of thoughts, grandiosity. So feeling, you know, more important than usual or like you can do more or be more talented just as a kind of a clinical pearl. When people are asking questions about this, I think people often will say to patients, Did you feel like you had special powers? And nobody almost never do people endorse that. But what they will endorse is feeling more talented than usual. So that's a bit of a pearl. And then other things are distractibility, increased goal oriented behaviour. So you get patients who will do things like clean their whole house in an hour or write a book in a way that they wouldn't otherwise. And then risky behaviours which are usually things like risky sexual behaviours or spending or reckless driving or using drugs and alcohol that they wouldn't typically do.

  Jordan: [00:05:01] All right, So you just dove right into the DSM criteria. So maybe let's pause for a second, make that really explicit.

   Luke: [00:05:09] Yeah. So I think so. The DSM specifies a criteria for mania. And the core symptom of mania is this idea of the elevated mood. And I think there's kind of this image out there that that people think of of mania as this high, euphoric, happy state. And and that's not always the case.

  Dr. Mark Sinyor: [00:05:27] It's definitely not always the case. You'll often find people who are quite irritable or agitated. And it can be an issue, certainly. And, you know, in terms of people getting into trouble in the community, either getting into fights with people or, you know, having to be brought in by police. So definitely don't forget about irritability, although that's the classical mania is someone who's kind of euphoric and, you know, really happy to be that way.

   Luke: [00:05:52] And you mentioned many of the other criteria for mania, and there's an acronym that's often taught, at least at the University of Toronto, to to describe them, which is  GSTPAID like paid. So maybe we can go through and talk about each of those things that that you touched upon and just kind of blow it up in a bit more detail. So the G is stands for grandiosity. And you mentioned that that the classically were taught to ask, do you have any special powers and actually that very few people really endorse that explicitly. And you mentioned a few other ways of asking about it.

  Dr. Mark Sinyor: [00:06:27] Yeah. I mean, I guess it depends. Obviously, often you can see it if someone is acutely manic, but if they're not a manic at the moment, usually you want to ask things like during that period of time, which by the way, I think I just realised I said four days it should be seven, that during that period of time, you know, Were you feeling more talented than usual? Did you feel like you could accomplish things that other people couldn't necessarily or that you usually wouldn't be able to accomplish? And and it sort of connects up a little bit with the one about activities. You want to ask people what they were doing, Were they writing excessively or were they? And then what was the content of that? I was writing something because I was going to make the next great novel and I'm not a writer or I was going to solve all the scientific experiments or equations and things that I have no background in science. That's the kind of thing that you'd see.

   Luke: [00:07:15] Like an elevated sense of kind of what they can accomplish.

  Dr. Mark Sinyor: [00:07:18] Yes. Self importance and.

   Luke: [00:07:20] Self-importance. Yeah. And you also that that also touches upon, I think, the idea of activity which is what the A and  GSTPAID. that there's increased goal directed activities.

  Dr. Mark Sinyor: [00:07:29] Yes. So almost always people will feel like they're getting more done. I know we're going to get to it later, but the distinction between hypomania and mania, but often in hypomania, people actually are getting things done. When people are floridly manic, usually they're too ill to be able to do things. So what they'll describe, at least in retrospect, is that they thought that they were doing all kinds of they thought that they had written the greatest book. But when you're assessing somebody and they present you with some of the material that they're working on, often it can be gibberish or unintelligible.

   Luke: [00:08:01] And some of the other activities that they engage in, which is the P for for pleasure seeking despite painful consequences that also kind of factors into some of the activities that they do.

  Dr. Mark Sinyor: [00:08:11] Yeah, if you think about it as being an acute episode where people are, you know, euphoric and don't necessarily have good judgement about what's a good activity or not, they become disinhibited and they, they can do things that they really wouldn't otherwise do. People will talk about having unprotected sex or spending thousands and thousands of dollars that they don't have or, you know, saying, you know, I never touch alcohol. But when I was manic, I, you know, I had 30 drinks in one day and the other. By the way, key point, when you're taking a history either from a patient or from collateral about that is, you know, if it's if they were taking cocaine or a stimulant or something else that could induce a mania, was it before or after? If it happened before, it could actually not be bipolar disorder or it might be a substance induced or an amphetamine induced bipolar disorder as opposed to bipolar one disorder. On the other hand, many, many people with bipolar disorder will say, no, no, no, I was manic for three or four days and I never used cocaine, but then I didn't mind. It was no big deal. So I just had a bunch of cocaine. Right. So that would be more in terms of the risky pleasurable behaviours.

   Luke: [00:09:16] And I think you've mentioned some of the S's of the pleasure of activities, sex spending substances which are common spheres that people experience, difficulties that also I think touches upon the idea of impulsivity in bipolar in a manic episode.

  Dr. Mark Sinyor: [00:09:38] Right. So, I mean, people in a true manic episode, people don't typically have a lot of control over what they're doing. You know, I don't know if we're going to go into the pathophysiology, not that we know exactly how it works, but sometimes mania has been at least colloquially described as a brain being on fire. Mm hmm. You know, people are just doing everything around them. And if you've ever seen anybody who is manic, it can often be quite, quite jarring.

  Jordan: [00:10:02] And I think that ties in nicely with the D in  GSTPAID. of Distractibility in that people can be highly responsive to stimuli that are around them. So if you see somebody and they emerge and they're in a manic episode, you can see them kind of paying attention to people who walk by the room. They're shuffling papers, they're rummaging through things. They become kind of like really focussed on a fold in the clothes that they're wearing or a pattern that they see. So it's interesting how all of these things blend together. So we've covered grandiosity. So the G, the P, the A, the D. And I think now maybe you mentioned the sleep thing.

   Luke: [00:10:42] Yeah. You were talking about like the increased energy of doing all of that. And you mentioned that that rarely do you ever see a mania without the sleep component.

  Dr. Mark Sinyor: [00:10:51] Yes. I mean, I think I think the other thing is that sleep is often the trigger for mania. I don't know if we get to that, but when I see patients who have this diagnosis, we spend a lot of time talking about things like making sure you never have an all nighter and don't work, shift work and be extra careful about your medications when you're going overseas or might be jet lagged. We know that pretty much all antidepressants can induce a mania so people can become manic on standard antidepressants. They can become manic when they get ECT which is an anti depressant. They can become manic with light. Often mania happens in kind of March, April, May, the time period where there's a sudden increase in light. And we know that light is an antidepressant for people, especially with seasonal depression. And so total sleep deprivation actually is an anti depressant and major depression. The problem is it also, like all these other things, induces a mania. And so it's not only an important feature of mania, but it's often one of the most important causes. And one of the major treatments is actually to tell people that they absolutely must protect their sleep if they have a risk of this.

   Luke: [00:11:56] So sleep is both a symptom and a cause of manic episodes in some ways.

  Jordan: [00:12:01] And just to be explicit that we're talking about a decreased sleep. So the classic question that you'll see kind of experience psychiatrist asking emerges, are you finding that you're needing to sleep less but your energy as still as hot or even higher? And, you know, I've talked with patients who are sleeping like one hour a night for four or five nights, and they don't have any problem with that whatsoever. The last two, I believe, that are in  GSTPAID. are two related topics, ones that I've often got confused in the past. The T stands for Talkative.

  Dr. Mark Sinyor: [00:12:34] So people definitely will have a kind of a motor mouth phenomenon. One of the mental status aspects of patients who are in the midst of a mania is at least loosening of associations, if not flight of ideas. And what that means in plain speech is going from one topic to another topic to another topic in terms of their thoughts without necessarily being able to connect them up. And so that manifests in the same sort of thing orally when people talk.

   Luke: [00:13:04] So there are two kind of different manifestations of that's very similar, or this may be the same and the same phenomenon.

  Dr. Mark Sinyor: [00:13:09] Yeah, I mean, it's the it's the vocalisation of what's happening inside.

  Jordan: [00:13:14] So that was the T for talkative and then the I for ideas as in racing thoughts or speech that presents ideas all over the place. And you'll hear psychiatrists use the term flight of ideas to kind of like almost describe it as though these ideas are taking off.

   Luke: [00:13:29] And so in order to be diagnosed with a manic episode, then you need to have the core symptom, which is what we talked about, of the elevated or irritable mood, as well as at least three out of the seven of these of these criteria. In addition, and as you alluded to, Dr. Sinyor, this episode has to at least for at least one week, for it to be classified as a mania with certain caveats that if a patient requires hospitalisation before that time, then this becomes the episode is automatically classified as a mania for this syndrome.

  Dr. Mark Sinyor: [00:14:00] Yeah. I mean, we can get into a couple of the difficulties of of the DSM classification. One of the things is that, you know, retrospectively, you know, part of the reason for the seven day choice is because many people can feel giddy or hyper for all sorts of different reasons for a few hours. And they want to really try to distinguish these things. But, you know, if someone has all of these symptoms for four or five days, is that not a mania? I think this is where we need to all use our kind of clinical expertise and judgement.

   Luke: [00:14:27] Absolutely. The other thing that we should touch on is the idea of the mania can present with or without psychosis. So psychosis, which we'll cover in detail at a later episode, is in essence the presence of either delusions or ideas that are fixed and false in a patient's mind. Or hallucinations which can be auditory or visual in nature and and or presentation, the disorganisation of their thought process. So there are presentations of mania which present with psychosis and without.

  Dr. Mark Sinyor: [00:15:01] Right. And the an important point is that typically the psychosis in mania is a is a grandiose delusion. So a belief that the person is the messiah or that they're going to be the next Bill Gates or, you know, the next president of the United States. You should also just generally for all mood disorders, that would be what's called mood syntonic delusion. Sometimes you can get dystonic delusions. So in other words, if you have someone who's depressed, who has a grandiose delusion about being the Messiah, that would be kind of opposite. And in the same way, if you're manic and you have a delusion that you're going to lose all your properties or your body is rotting from the inside, you know that that would be dystonic. There isn't much to say about that other than dystonic delusions seem to be a poor prognostic sign. And also, if you have both, you also have to think about a mixed episode, whether there are also symptoms of depression at the same time.

   Luke: [00:15:57] Mm hmm. So. Grandiosity, less sleep, more talkative, more pleasure seeking, more activity. Flight of ideas and distractibility. That just sounds like somebody who's just in in a summary, like someone who's just way too wired. And it sounds like it kind of describes the initial case quite well.

  Jordan: [00:16:20] Yeah. So, you know, it's kind of interesting because somebody who is in the throes of like a full manic episode, like in our case, they're actually pretty easy to diagnose. This guy comes in almost like right out of the textbook. So just to summarise and touch on some of the symptoms and connect them to the criteria that we just went over. Grandiosity. He is saying that he is Jesus, that he's a king. So that's a symptom of grandiosity or a sign of grandiosity. His he seems like he's talking fast in the brief experiences that we've had there. So that's two we know from his partner when he came in that he hasn't slept in three days. So there's sleep. It doesn't seem like his mood was elevated from the way that he was describing it and kind of the way that he's acting.

   Luke: [00:17:09] So he's taking off a lot of the boxes already.

  Jordan: [00:17:12] Yes. Yeah.

   Luke: [00:17:13] So he's so so we haven't even seen him. But based on what we know already, it sounds like he could be manic. So so the next step is really kind of going to see him interviewing him and trying to see if we can find out more. And in assessing someone who is in the throes of a manic episode, can can pose some pretty unique challenges.

  Jordan: [00:17:32] Yeah. So I think this is where it would be great to hear your sort of take on this as well, Doctor SINYOR. But, you know, I can start things off from my own experiences in the Emerge. An acutely manic patient can be one of the harder, more intimidating patients that you can see and emerge. And part of that is because of the intensity of their affect and also their distractibility and impulsivity so they can be so distractible and sped up that they cannot provide clear answers or they may be very irritable, impulsive, to the point where safety becomes a concern. So, you know, the approach that I take is in contrast to many other patients that you interview in a mental health setting, you want to try and keep your questions actually quite closed. An open ended question with a patient who you have a high suspicion of mania is just going to allow for room for their flight of ideas, and then you're stuck in a situation where you have to cut them off, which can be tricky. So it's better to actually try and stay one step ahead of that and ask really simple, close ended questions with simple answers and move at a rapid pace. So you need to come in quite prepared with sort of your list of questions and saying, okay, this is my agenda, I'm going to try and move through it.

  Dr. Mark Sinyor: [00:18:46] Yeah. So as you were saying, Jordan, I mean, you know, for everybody, the first step is always safety. And these certainly I mean, for the most part, you're not really in danger with a manic patient, but some of them might be. And so, you know, you have to be cautious when you're going in your attention to sort of your distance from the door, not necessarily barring access, but being able to to kind of get out safely and not necessarily hovering over or being within too close distance with the patient. And I agree with you with your approach. You know, the the most important thing to do when you have a patient who's manic is to take a mental status. The mental status may actually give you everything or at least the most that you're going to be able to get. And then my I agree with your kind of approach to say, you know, what are high yield questions about things like psychosis or about what what moods been like or just trying to get some understanding of what the person is thinking at that specific time about whether there are any grandiose delusions? You know, how you know, what have you been doing recently? What you know, what are your.

  Dr. Mark Sinyor: [00:19:42] Are there any special talents that have been coming up recently? And then I think as we're about to get to most of what you're really going to try to do is to get collateral history. That's going to be the most important thing. So the good news, just to comment about the interview, you know, I don't want to ever send a medical student or a resident or anybody to go see a patient and not take a complete history. But if you really think mania is what's going on, and that becomes should become fairly apparent in the kind of case that you're describing, you're not discharging the person. A mania is a you know, is it a medical emergency, a psychiatric emergency. And so and with the most important thing of getting the person to sleep, you know, fairly rapidly. So what you want to do is do the kind of assessment that you can get, whatever data, you can get that collateral and then give them the right treatment to to arrest the manic episode as quickly as possible.

  Jordan: [00:20:33] And I wonder if this is maybe a good point. For an aside, this is something that sometimes I will say to patients or to patients family members is that it seems like we're increasingly realising that manic episodes are like neurotoxic in a way. And so it's not just like, you know, are we is this person a risk of safety to themselves and others at this present time? But like, are we letting a pathological process go on if we don't treat it, that has implications down the line. Do you want to speak to any of that research or.

  Dr. Mark Sinyor: [00:21:01] Well, there's there's definitely a research suggesting a kindling phenomenon which essentially suggests that initial manic episodes are often provoked by a very significant either physiological or life stressor, and they're usually fairly easily treated and people who tend to have repetitive. Manic episodes seem to be able to get into them faster and to be harder to treat. And so for very much the kind of reasons that you're describing. And so that's the reason it really is an emergency. And what you want to do is to try to arrest it as quickly as possible. And then in many cases, just like you see in patients with schizophrenia and other severe and persistent mental illness, you have patients who say, well, I like being manic. It was really great. Please can't I just do that again? And part of the education is really around what you're describing, which is to say, you know, to commiserate. Yeah, I know that you liked it, but remember that you had to be hospitalised and it wasn't, you know, in the end it wasn't very good. And number two, I can treat you now, but I may not be able to treat you as effectively in the future if we don't make sure this doesn't happen.

  Jordan: [00:22:02] So coming back to some of the tips about interviewing an acutely manic patient, some of the other things that I think were passed on to me and I really value is remembering that the emotion in the room can be infectious and you can really see that with mania. If someone is really euphoric and they're silly, you can find yourself laughing. Or if somebody is really irritable, you can find yourself getting irritable or nervous. And it's important to sort of think about how their emotions are going to impact your emotions and how to sort of handle that during the interview to still be an effective clinician. Another thing is that often these patients can become very person like try to relate to you personally. They can ask like intense personal questions. They may be sexually inappropriate. And so that's something to be aware of and to be prepared for it, really. And if that happens to deflect and not engage in that way.

  Dr. Mark Sinyor: [00:22:56] It's not written anywhere as a diagnostic sign, but perceptiveness and incisiveness and being able to kind of get get at specific things that are really going on. Often manic patients will give incredibly insightful comments about something that's going on. You know, if you're really tired or something, they'll they'll pick up on it because they are attending very much more to everything in the environment. But yeah, I mean, I think the key thing is obviously to attend to your professional boundaries and when you're doing interviews in all of psychiatry, what you want to do is to, you know, you have to find a way to empathise with a patient, right? So if you have a depressed patient, you know, you don't want to be laughing and being silly. That would be an empathic and unkind. But you also don't want to start taking on their depression. The interview won't work and it won't go anywhere. So it's sort of the same sort of thing. In mania, you kind of want to show the patient that you're listening and that you're attentive to what's going on, but you don't want to mimic their their mood.

  Jordan: [00:23:48] So some of the you mentioned some of these already, but for our listeners out there to rehash it, some of the key content, if you have a limited time with the patient, some of the key content that you want to try and find out are recent stressors. Have they changed their living arrangement? Is something going on at work? Is there a financial situation? Is there a relationship issue? You know, is there any thing you can pick up about concrete events that would give you a clue that somebody has been doing risky behaviour? Like have they been sexually active more so than usual? Have they been gambling more so than usual? Have they been speeding? And it's nice to try to tie these to concrete events to give you real kind of data to go off of if you can. It can be hard, but try and pin down a timeline for the mood change. So is this something that's been going on for hours? Is it days? Is it weeks? That has very different implications. And really and we'll mention this over and over, the sleep is just so important. So if you could get one thing out of somebody who you're suspicious might be manic to get a sleep history. And again, concrete data like how many hours have you been sleeping and how many days has that been going on?

  Dr. Mark Sinyor: [00:24:55] I would add to this list, although I know for sure you would ask it anyway, or of the collateral, but medications and substances essentially for for two reasons. One is for diagnostic clarity. The substances can sometimes help and a very large percentage, or at least some large percentage of these patients are going to have are going to have an anti depressant or some other medication on board. The median length of time to an appropriate diagnosis of bipolar disorder is 12 years. So it's easy when the first episode is a manic episode, but for a very large percentage of patients, they're going to get multiple depressive episodes and then become manic. And often that will happen on an anti depressant inducing a mania. And of course, you want to stop that right away if someone comes in. So that's the other the other thing you really need to know right off the bat.

   Luke: [00:25:36] So armed with with this kind of thought about the approach to interviewing the patient, we're going to go we're going to the room to try to interview Devin. And and what ends up happening is he just keeps saying, I am king of the world and then starts kind of going off on tangents and you ask about sleep and he says, Sleep country, I'm king of sleep country, da da da da da. Just kind of goes off on tangents. We can't get very much, even when we try to ask close ended questions.

  Jordan: [00:25:57] As Dr. Senor said, the mental status there, even just a couple of minutes, is almost enough for you to make a diagnosis there. So we see that that's flight of ideas. And now we go back to take a collateral history, which in patients in an acute manic episode is extremely important. And I'm not sure if we've explicitly described a collateral history before, but basically it. Means going to friends, family. Anybody who knows this person well to try and hear about what's been happening with them. And that, I should add, is one of the things, if you're seeing somebody who you suspect is currently in a manic episode and you have very limited time and you know that nobody's brought them to emerge, that's something that I'll try and do is like, can I get a phone number for like anybody who's been hanging out with you the last little while so we can try and hear a bit about what's going on.

   Luke: [00:26:45] So in Devon's case, we have his partner who brought him to the merge so he can talk to him. So this is what we find out. Devon has been busy with work and sleeping poorly for the past two months, and about two weeks ago, he received an interview for a dream job in his field. And that's when Ben started to notice changes in Devon's mood and behaviour. He was sleeping even less, but instead of being fatigued, he was more energetic. And he started saying that it was the best he's ever felt in his life. He became filled with ideas for the interview, some of which didn't make a lot of sense. Started making a list of hundreds of things that he could do, like making a documentary for pharmaceutical development. But then he would drift from one thing to another and never really complete anything. And Ben initially thought this was all excitement and anticipation to do with the job interview. But then about five days ago, it reached a breaking point when Devon started talking about using his new job to take over the world and that he had a vision from God and that Ben checked their joint bank account and realised that he had spent thousands of dollars online. He tried to convince Devon's to stay home and rest, but then Devon ran off to work and he ran through the office. And that's how he ended up being brought in to the hospital.

  Jordan: [00:27:47] Okay, So now we know he's got decreased need for sleep, increased pleasure seeking despite painful consequences, and which would be the spending and increased goal directed activity, which was that sort of unfruitful activity that he was doing to try and prepare for his interview. So I would say at this point in time, he almost definitely meets criteria for a manic episode.

   Luke: [00:28:07] So one of the most important information that we can get from assessing the patient in the room is the mental status exam. And so I want to spend a few minutes maybe talking about what some of the common things we might see for somebody who's in an acute manic episode.

  Jordan: [00:28:20] Yeah. So for our listeners who have listened to the earlier episode on depression, we use the mental status exam that goes through appearance, behaviour, cooperation, speech, thought, form, thought, content, perception, mood affect and safety in different institutions, you'll see a slightly different order. Maybe the terms are used interchangeably, but in general this should cover the majority of the standard sort of mental status assessment. So usually we start with appearance. So what does the patient look like and something you can do from outside the room? What are some of the things that you might expect looking if you're if someone is in a manic episode, what sort of things might you notice about their appearance?

   Luke: [00:29:06] Well, I think you're looking for signs of the symptoms that we talked about previously. And so if they're feeling really grandiose and they're let's say they believe that they are the president or they are God, they may dress to to represent that in ways that are atypical or in our patient's case right now, I think he's ripped a shirt off and running around the emergency room half naked. So that's one of the things that that that we might see in terms of behaviour. I think we also talked about the increased energy, the increased kind of activity in the room. So we might even call that agitation or psychomotor agitation, pacing, gesturing, and we talked about maybe kind of not not as respectful of personal space and being kind of flirtatious or even aggressive with people. Other people in the room sometimes say in terms of cooperativeness, I think there's you can see a very variety of presentations depending on what their mood is like at that point in time. If they're feeling elated and grandiose, they may be very happy to talk to you, even though their speech may not make sense. But if they're feeling irritable, they may be insulted or slighted by the smallest thing you do, and they may tell you to to get out or or do their swear at you.

  Jordan: [00:30:22] In terms of speech. This is one that you would almost certainly expect to be abnormal in someone who's in an acute manic episode. So they'll have a lot to say. So there's an increased increased production of speech, There's a high volume of speech. Sometimes there's more prosody, like there's more emotion and fluctuations in their speech. And there's you can comment on their reduced turn taking. So they're kind of just talking over and over and over you. They don't really allow for a natural pause in a conversation for which you normally sort of expect. And do people having a conversation.

   Luke: [00:30:59] It's an interesting point about pressured speech is that I've often you know, it's the you think of classically the really fast speech, but I've seen presentations of mania where it's not very fast, but it's just there's very no breaks in their speech. So they're not talking extremely fast, but there's really no endpoint. And they keep going and going and going, and it's really hard to cut it unless you're thinking about doing that.

  Dr. Mark Sinyor: [00:31:20] And that, by the way, for the listeners is actually the definition of pressured speech. So that's a term that people may hear. It actually implies uninterruptability. It's difficult to get a word in edgewise. That's the definition.

   Luke: [00:31:32] And that might be reflected in the way that their thought process is also in that that they would go from one idea to another to  and to another. And so, you know, in someone who can you can follow logically, we would call that logical and goal oriented in mania that that may progress to tangential reality where they're taking their ideas or taking off from one thing to another. Or circumstantiality where they seem to be over-inclusive, but they do eventually come back. And in the most extreme of cases, we have what's called flight of ideas, where it's even it's hard for for you to even follow along exactly what the association is that the patient is making.

  Dr. Mark Sinyor: [00:32:11] I think part of the distinction is in circumstantial thought people are over inclusive and they may be including detail that is unnecessary, but they're kind of they're going from point A to point B, There's something that's in between called loosening of associations where they're kind of going from point A to B to C, and you can kind of see the connection between the two, but it's not that logical. It's sort of starting to break free a little bit from the way that one would normally think in flight of ideas. The definition is literally that you're bouncing from one idea to the next with no clear kind of connection between any of them.

  Jordan: [00:32:45] Sometimes I've seen patients in acute manic episodes make like their their sentences are connected by rhymes or word structures. So you can see some pretty interesting speech and thought form abnormalities. In terms of thought content, you're looking for mostly grandiose themes in a patient who you're expecting would be in an acute manic episode. They may describe themselves as possessing a secret or greatly important knowledge. And we've sort of talked about this idea of like, Oh, I'm going to write a novel, but I've never done that before, or I'm going to cure cancer, even though I have no background in cell biology or something of that nature.

   Luke: [00:33:31] And we talked about kind of mood congruent themes and mood incongruent themes in terms of delusions that people may have and similar to that. So other psychotic features that you're looking for would be perceptual abnormalities. So auditory or visual hallucinations, are they responding to different stimuli in the room that you may or may not be aware of? And just trying to get a sense for that?

  Jordan: [00:33:56] Yep. And then coming back to Mood, which is how somebody was describes their own mood and so they might say it's fantastic, excellent. Never been better. But it can also be very irritable. And so they may report being really angry, frustrated, especially if they feel that they're in they emerge inappropriately or angry. And as a reminder to listeners, we separate mood, which is what a person sort of says about how they're feeling with affect, which is how we perceive their emotional state. And here we can see a pretty wide range. So it's an expansive so it seems like they just. I it's hard it's almost hard to really concretely describe, but it's like they feel connected to other people. Like they feel like they can just talk to anybody. They feel like they're kind of, I don't know, they're almost in like this flow state versus, you know, you can see someone who's being like, joyous or euphoric and you can also see people who are very angry.

  Dr. Mark Sinyor: [00:35:00] Another component I would just add to that is that you often see lability. So being able to rapidly switch from one thing to another. So you might have someone who's laughing and giggling and then suddenly they'll become irritable for some reason and then they can bounce back and forth. Mm hmm.

  Jordan: [00:35:13] Yeah. Because when we describe affect, it's not just the quality of what we're seeing, but we're commenting on like, what's the range, what's the reactivity and.

   Luke: [00:35:22] The intensity.

  Jordan: [00:35:22] Intensity and all of these things. We expect to be sort of more extreme. More extreme, Yeah. And then lastly, of course, as an important part of any mental status exam and any psychiatric assessment is safety. And when we talk about safety, we talk about suicidal ideation, so safe self safety and homicidal ideation or the intention to harm others. And manic patients can be very impulsive. They may be more likely to use substances. They may develop psychotic symptoms related to persecution or paranoia. And these factors really can heighten the risk of a harmful event.

  Dr. Mark Sinyor: [00:35:57] And just on the point of suicidality, as a as a researcher in the area, I feel obliged to comment on it. The I mean, as people might expect, it's more likely to die from suicide and bipolar disorder during the depressive phase of the illness. But people do die if they're manic. They might have an idea that to join God, they need to do something to end their lives or something, you know, something of that nature. So definitely you need to ask. And don't just assume because they're super happy and elated that that isn't a concern.

   Luke: [00:36:23] I've also seen safety risks where people believe they can fly as part of their grandiosity, and so they jump off a building. So not not explicitly with an intention to kill themselves, but resulting in potential significant safety concerns.

  Jordan: [00:36:36] Yeah. And also related to there's some of their impulsive behaviour, like I've seen people who are speeding, like they're going like 200 kilometres an hour on the VW because they just, you know, that's not a problem for them.

  Dr. Mark Sinyor: [00:36:48] And so it's a bottom line. Attend to safety. Yeah.

   Luke: [00:36:52] And so, so you know, so we talked about manic episodes, and manic episodes are kind of associated with the word bipolar disorder. And so the criteria is what's the difference between someone who has a manic episode and someone who has a bipolar one disorder? A diagnosis of bipolar one disorder can be made with the presence of a single manic episode, and there's actually no requirement for a depressive episode in the criteria, even though most commonly patients present in depressive episodes, they spend significantly more time in depressive episodes know in a prototypical bipolar disorder.

  Dr. Mark Sinyor: [00:37:24] By the way, for that reason, people who only there there are it's more of the rare patients. Maybe we don't see it as much who have only manic episodes, and that's actually a good prognostic sign. People, you know, who come in and might have one manic episode once every ten years at 20 and 30, actually, generally they do pretty well. It's the folks that fall into multiple depressive episodes that can be in trouble.

   Luke: [00:37:47] And in order for you to be diagnosed with bipolar disorder after having had a manic episode, it's important to rule out some of the other diagnoses. One of the one of the diagnoses that we talked about, which is often difficult to separate because the substance is substance induced mania. So, for example, somebody who was high on cocaine coming in, talking really fast, lots of energy, pacing in the room would actually tick off A lot of first of all, even in the phase of acute intoxication, can look like somebody who is presenting in mania. But also there are syndromes whereby even after the substance is cleared, people can have some period where they're meeting criteria for a manic episode.

  Dr. Mark Sinyor: [00:38:29] So sometimes that's difficult to disentangle. But you really do expect that after the cocaine is out of the person symptom that it'll resolve. The longer the symptoms persist in the absence of the drug, the more you have to be suspicious of an underlying bipolar disorder. The other just comment about I don't know if we should count this as substances. But the change from DSM four to DSM five in DSM four, if you were put on an antidepressant and you had a so if you were put on an antidepressant or you were put on cocaine and you had mania, it would be considered a substance induced manic episode. In DSM five, it maintains that for cocaine, because everybody who's on cocaine gets a bit manic or most people will have something like that. But it acknowledges the fact that most people, when they start an antidepressant, shouldn't become manic. And so if you have that predisposition and that happens to you, then it puts you somewhere on the bipolar spectrum. And so DSM five says that an antidepressant induced mania still qualifies you for a diagnosis of bipolar disorder.

  Jordan: [00:39:31] So when we're trying to make a diagnosis in a patient that we have other than just waiting to see if things clear, we want to make sure if we can we can get a urine tox screen if it's someone that we don't know anything about, to see if there is any substances in their urine and try and get collateral history about drug use and try and sort out the timing as well, because we know that sometimes if people become acutely manic, then they become impulsive and they use substances and so on time, course there is useful.

   Luke: [00:40:00] Another one that often get misdiagnosed between bipolar disorder is borderline personality disorder. And that's a pretty complex subject. But in short, people with borderline personality disorder can also present with mood fluctuations that they sometimes self label or label by others as being bipolar. They can have impulsive behaviour and and can present with transient kind of psychotic symptoms. So so how would how does one often separate out kind of a personality disorder from a bipolar disorder?

  Dr. Mark Sinyor: [00:40:32] So usually it's actually easier when you're seeing someone in a manic episode, but even then it can be difficult because, you know, patients with borderline personality disorder who are having a borderline crisis or a rage can actually look even in that circumstance like someone with bipolar disorder. So cross-sectional, it can be difficult. Another thing that makes it difficult is you can get people who have both bipolar disorder and borderline personality disorder. But the distinction is that people with borderline personality disorder have poor coping skills and affective dysregulation that's really chronic. I mean, without treatment, it's something that should be there a lot of the time or most of the time in bipolar disorder, if that's all you have, if you don't have a co morbid personality disorder, it should be episodic. The symptoms that we're describing here should start acutely or sort of at least subacute early. They should go on for a period of time. They should be arrested. And then afterwards the person should look back and say, well, I would never act that way. That's not part of my usual experience. And so that's usually the best way to make the distinction is that kind of chronicity versus episodic. You know, the other thing obviously, is that a strong family history of mood disorders and things like that would predispose you more to bipolar disorder phenomena logically. On the other hand, you know, a childhood victimisation and invalidating environments and abuse and things like that would all be kind of push you into thinking more about borderline personality disorder.

  Jordan: [00:41:53] A great summary of something that is really challenging and I think the key there is to to certain extent to remain humble when you're seeing a patient in emerge. That cross sectional diagnoses are very challenging and this is where we can use collateral and sort of big picture thinking to say, okay, this is what this person looks like now, but like how are they in the rest of their life? And that really highlights the importance of collateral in these patients to say like, is this something that's been going on for two weeks or 20 years?

   Luke: [00:42:22] Another challenging thing to separate out is especially when they're presenting with manic episode, with psychosis, to separate out from a primary psychotic disorder like schizophrenia or or something like schizoaffective disorder.

  Dr. Mark Sinyor: [00:42:33] So going back to our DSM criteria, a primary psychotic disorder requires you to have psychotic symptoms for a period of time in the absence of mood symptoms. And you can't figure that out. I mean, certainly when you're just laying eyes on someone who isn't giving you a very good history. So it's back to to Jordan's idea. But, you know, requiring a cross sectional sort of history. And if it isn't so clear to be humble and honest and say, we don't really know and we'll have to follow you and look at what the course is, and then we'll we'll kind of give you a revision about what the diagnosis is.

   Luke: [00:43:04] So time is an important factor in separating out some of these differential diagnoses.

  Dr. Mark Sinyor: [00:43:09] Can I just one other thing that had come up earlier was the distinction between or actually, I think no, I think you're going to get to it as mania and hypomania. So maybe I'll let you do.

   Luke: [00:43:17] Actually, that's perfect. Actually is actually where are we going to go now is talking about this idea of the hypomania versus mania.

  Jordan: [00:43:25] Because I think that's I mean, if somebody walks in the door and they meet six out of seven  GSTPAID.criteria and they're talking about being king and the messiah, you know, that's pretty clear cut. Right. And but I think what's really tricky and why you we see this data about the median time to diagnosis of bipolar being 12 years is that people don't often walk in in full blown mania. Right. So, Dr. Senior, why don't you walk us through hypomania.

  Dr. Mark Sinyor: [00:43:49] Yeah. So for hypomania. So a couple of distinctions. The one that I mixed up at the beginning. So for mania, it needs to be seven days, although again, everybody who's manic for seven days was also manic for one day or two days. So you don't have to wait really for seven days. If the whole picture starts to become clear. Hypomania can happen over a shorter period of time, so it can be only a few days long. You still require three out of the seven g GSTPAID criteria to be present. But the major distinction is around severity and functionality. And actually that was what I was going to jump in to mention. So things that would be markers of higher severity are psychosis. So if there's psychosis as part of the picture that pushes you into mania, if and here you have to make a bit of a judgement call, but if the person is impaired, then that also graduates a person to having mania again with this distinction that people who are hypomanic may feel a bit elated and they may be different, very clearly different from the way that they are when they're not hypomanic, but they're still doing things they may even be achieving more than expected, getting more work done in a productive way, whereas people who are suffering from a mania will not.

  Dr. Mark Sinyor: [00:44:58] And so that brings us to the third option, which was mentioned before. That was what I really wanted to clarify was the hospitalisation. So if you've had a hospitalisation, it qualifies you as mania. As far as I know, it's the only case in medicine where the behaviour of the doctor changes the diagnosis. So if we choose to hospitalise, it gives you bipolar one and if we choose to send you home, it's bipolar two. So this illustrates some of the limitations of the DSM. And the key point is that the hospitalisation is a proxy for impairment. I mean, if a person is hypomanic and they've been hospitalised because they don't have anywhere to go that evening, that shouldn't give them a diagnosis of bipolar one disorder. On the other hand, if someone really laid eyes on the person and said that you're impaired, something's really wrong here and they required a hospitalisation, then then that makes sense to kind of elevate it to that kind of more severe diagnosis of a mania rather than a hypomania.

   Luke: [00:45:48] So right now in the DSM, we make a distinction between bipolar type one and bipolar type two. As you alluded to and and as we talked about bipolar type one, you only need the presence of mania, even though these patients often spend long periods in depression. For bipolar type two to be diagnosed, you need to meet criteria for hypo for a hypomanic episode, and as well as having a met criteria for a depressive episode at a period in time previously. And my understanding of that is that because hypomanic episodes are often hard to tease out on history, that the requirement for a depressive episode is there is a way to kind of ensure that that you are getting closer to the diagnosis than if someone had come in with four days of feeling better than they normally do and maybe did a few extra stuff.

   Luke: [00:46:41] So today we use the case of Devin, our pharmaceutical representative, and we talked about mania and bipolar disorder. We talked about the criteria for mania, some differential diagnoses, presentations, the mental status exam in a manic episode, and some ideas for how to interview somebody and assess somebody who's in the throes of a manic episode. We went into talking about how that fits into the criteria for diagnosing bipolar disorder, bipolar one versus bipolar two, mania versus hypomania. And we talked a little bit about the sticky point of the differentiation between different types of bipolar. This has been psychEd. Thanks for listening.

  Jordan: [00:47:18] Thank you all so much for listening into this episode of Psyched. We are eagerly looking for listener feedback and you can give that to us by email directly at info at psychEdpodcasT.com or you can find us at our website psychedpodcast.org and at the bottom of our home page, there's a contact us section. We'd love to hear specific feedback about the episodes, structural feedback about the way we deliver the episodes, feedback about our website, show notes, future episode requests, you name it. We want to hear it from you. Big thanks to everyone who helped to write and produce this episode. Main writers were Jordan Bawks and Lu Gao, with assistance work from some of the other members of the Psyched board, including Alex, Lucy and Carrol in its early stages. Big shout out to our audio, Editor Henry Baron, for putting it together, making it sound real nice. Of course, none of this would be made possible without the support of the Department of Psychiatry at the University of Toronto. And of course, with this episode, a special thank you to Dr. Mark Sinyor for taking the time out of his busy schedule to help us out and provide clinical wisdom. And his expertise was fantastic. We'd also like to acknowledge all of music. Who was the artist responsible for our theme song that we use. So thank you so much for tuning in and hope to have you back soon.

Episode 2: Treatment of Depression with Dr. Sidney Kennedy

• Episode 2: Treatment of Depression with Dr. Sidney Kennedy

  Lucy Chen: [00:00:15] Welcome to PsychEd, the Educational Psychiatry Podcast for Medical Learners. Biomedical Learners. We are a group of first and second year residents at the University of Toronto in Canada who have come together to discuss important topics in psychiatry through our own research and with the help of our world class psychiatrists.

  Carrol Zhou: [00:00:35] Today's episode will provide a comprehensive overview on the treatment of depression as a continuation of our last episode on the diagnosis of depression. I'm Carol Zoe, and I'm joined by my co hosts, Lucy Chen and Alex Raben. We will also hear from Dr. Sidney Kennedy, the founder of the CAMMAT Guidelines on Depression, who sat down with Lucy and Alex to share his expertise in this area, as well as highlight some of the changes to the soon to be released 2016 guidelines that are different from the current guidelines from 2009.

  Alex Raben: [00:01:09] Our discussion will once again revolve around our case patient. We will start off by explaining what the CANMAT guidelines are. We will talk about the general approach to starting treatment and then we will delve deeper into each type of treatment and how and when they should be used.

  Lucy Chen: [00:01:26] So to start, remember, Erin, she's a 24 year old resident who's been experiencing fatigue, poor sleep, and is having a difficult time enjoying and concentrating at work for the past few months following the end of a long term relationship. In our last episode, we diagnosed Erin with a major depressive disorder. Now she wants to know what you might suggest to help her feel better. So where do we start?

  Carrol Zhou: [00:01:50] There are many different types of treatments for depression, and so it's easy to get overwhelmed. The CANMAT guidelines were developed to make this enormous task easier for psychiatrists as well as primary care providers. And although it does not replace clinical judgement, it provides an evidence based framework from which we can work from. As with any psychiatric illness, we want to take a biopsychosocial approach to treatment, and we also want to consider the culture and spirituality of the patient. Can that limits its scope to biological, for example, drugs and psychological, for example, psychotherapy treatments, Likely because social treatments are often region specific. For example, a specific crisis centre that you can refer to only in your city. And so we too will limit our discussion to these treatments with the understanding that in real life you may have additional options at your disposal. Let's hear from Dr. Kennedy, who gave us a better understanding of the CANMAT guidelines.

  Alex Raben: [00:03:02] Start. Could you just introduce yourself to our audience?

  Dr. Sid Kennedy: [00:03:06] I'm Syd Kennedy. I'm a professor of psychiatry at University of Toronto. I'm actually the founding chair of the Canadian Network for Mood and Anxiety Treatments. CANMAT and I've in recent years been the lead for the Depression Working Group. 

  Alex Raben: [00:03:23] Great.

  Lucy Chen: [00:03:24] Excellent. And perhaps you can tell us a little bit about CANMAT and where with the origins of CANMAT.

  Dr. Sid Kennedy: [00:03:33] So the origins of CANMAT can actually be traced back to a Chinese restaurant and College Street in Toronto, just across from the former Clark Institute. Now, Camh which where a group of us used to meet on a Wednesday for lunch and talk about some of the issues that we were developing in our research and our teaching and the idea of developing guidelines similar to guidelines that had been produced, for example, for Anti-infectives in Ontario was a model. We decided on different names. We thought about the Canadian Network for Mood and Anxiety Disorders. But that said, Can MAD, and we thought that was probably not very sensitive. So in fact the mood and anxiety treatments are CANMAT became the the term that we selected. This was a group in Toronto, but we had many connections across Canada, so we held our first meeting in 1995. I sit one of the airport hotels in Toronto, so we had people come from Vancouver, Calgary, Winnipeg, Halifax, various other centres across Canada, and we agreed on a guideline project As the first initiative we became incorporated as a not-for-profit corporation. We defined our goals as patient advocacy, education and clinical research, and we've actually developed guidelines in bipolar disorder, which have been frequently updated, and also in depression with the most recent guidelines now being 2016.

  Alex Raben: [00:05:27] Right. And you mentioned that you came together sort of around a common common issues. What were those issues and how do the can guidelines solve those issues?

  Dr. Sid Kennedy: [00:05:39] I don't know if we actually solved all the issues, but we did feel that there were a number of other countries or regions that had looked at ways to improve patient care. And I've always thought that you can really do two things when you're trying to treat patients, and it would apply beyond depression. But in this area we'll talk about depression. So you can think about doing the best with the treatments and the options that are available. And then you can think about the new options that you can develop through research. So our CANMAT guidelines were really designed to promote optimal use of existing treatments.

  Alex Raben: [00:06:24] The CANMAT guidelines has its own system of evaluating current treatments, as Dr. Kennedy explains.

  Dr. Sid Kennedy: [00:06:31] So there are many different formats of assessing evidence, and we have become somewhat more we've raised the bar in recent years. We've been influenced by the grade system, which has been particularly developed at McMaster and elsewhere. Level of evidence is based currently on at least two robust randomised controlled trials or a large meta analysis and where effect sizes have been reasonable and reasonable might be 0.6 or higher. So that would that would produce level one evidence, one RCT without replication. Several smaller trials could be considered level two evidence. Level three evidence is large case series and level four evidence is really clinical individual case reports. So how do we get from levels of evidence to recommended first, second or third line treatments? And the answer is that we add to the evidence base, clinical expertise or clinical common sense. So if I could give the example, for example, of a drug like Olanzapine or Zyprexa, which is an atypical antipsychotic, but is frequently used as an adjunctive treatment for depression, and it's actually from the efficacy point of view, it's a very good treatment. On the other hand, it's metabolic side effects. The weight gain associated with its use makes it actually a matter of concern, particularly for long term use. So while it might have level one evidence, it would have a level two or a second line recommendation. And another example quickly would be something like the monoamine oxidase inhibitor antidepressants that were developed in the 1950s. For many patients, they're actually very effective treatments. But the issues of dietary concerns, the risk of hypertensive crisis would make it certainly not a first line choice for treatment and in reality probably a third line treatment. But you could argue that it could have second line recommendation.

  Lucy Chen: [00:09:07] In CANMAT first line treatments, which are what we mostly will focus on in this episode, must not only have good evidence in the literature, but they must also be practical and useful clinically. An interesting feature of the CANMAT guidelines is in its question and answer format.

  Dr. Sid Kennedy: [00:09:25] What we did and what we have done through each of our edits and and additions is we've actually at conferences and at other settings, we've asked community psychiatrists, primary care physicians to tell us what questions they feel they would like answered when they treat patients with depression. And we've got a whole bunch of questions that have come in. We sometimes use a few slides and show the questions that have been asked and we ask, are there any other questions that are not here? So we have I think, one of the differences between the CANMAT guidelines and other, for example, APA or the Nice guidelines in the UK are that we actually take a question and answer format to try and keep it very practical and clinically relevant. And I would hope from a medical student or a resident perspective, that's actually a good thing.

  Carrol Zhou: [00:10:26] This question and answer format allows clinicians to jump in and quickly answer their treatment questions. CANMAT breaks the treatments down into four categories psychotherapy, pharmacotherapy, neurostimulation and complementary and alternative medicine treatments, which in CANMAT includes diet and exercise. However, in our situation with Erin, where we're faced with starting treatment for someone with a new diagnosis of depression, it can be difficult to know where to start. We've asked for Dr. Kennedy's advice on this, and here's what he had to say.

  Dr. Sid Kennedy: [00:11:00] The first step is making sure you've made a good diagnosis, making sure that there aren't other co morbid disorders ruling out that this is actually a major depressive episode and somebody with bipolar disorder looking at things like psychotic features because those are all issues that would alter your treatment selection. And then we've tried to go into the issues, particularly of so-called specifiers, like you might have a seasonal pattern to your depressive episodes. And so that would influence the use of a light box as part of the treatment, not necessarily the whole treatment. Or you might have atypical symptoms, which means you would eat more and sleep more rather than typically sleeping less and eating less. And does that change your treatment? Some people would say there have been trials to suggest some treatments. Others would say it doesn't really change your treatment. So those would be the first things I think you can think about the treatment selection, what are the patient variables? What are the aspects of the patient I should also mention. If a patient is if there are life threatening issues, acute suicidal beliefs, recent actions, severe emaciation or you know, these are the issues that are going to make you decide whether the person needs to come into hospital or not. So we've primarily tried to take people through the the thinking that would probably help you pass your membership exam if you were being asked these questions before you then start into the treatments.

  Alex Raben: [00:12:41] As Dr. Kennedy mentioned, it's important to first get the diagnosis right. We talked all about how to diagnose depression in the last episode. So if you want to learn more about that, go back and have a listen. If there are safety issues such as the patient being actively suicidal, then the treatment approach would be completely different than what we're going to talk about today. But we don't have these concerns for Aaron at the moment. One thing we didn't discuss in the last episode is diagnostic specifiers. These are labels that relate to each DSM diagnosis that have their own criteria. One important specifiers for Aaron would be the severity, which can either be mild, moderate or severe. These categories are subjective, but mostly depend on the severity and number of symptoms, as well as the degree to which the disease impacts the patient's life. Although Aaron finds her low energy and poor concentration distressing so far, she's been able to cope with them and has continued to function well at work. Therefore, her depression would be considered mild. This will help inform our treatment going forward. So after these general considerations, you and the patient are left with the decision of which therapy or therapies to initiate. Let's go through each of the domains. We will start with Lucy, who took a deeper look into psychotherapies for depression. First of all, Lucy, what exactly is psychotherapy?

  Lucy Chen: [00:14:19] Well, essentially psychotherapy is a non medical treatment that aims to help patients change the thoughts and behaviours that contribute to depression. There are many forms it can take, but the main aim is to change the pathological thought patterns that make people feel low or down about themselves.

  Alex Raben: [00:14:38] So when is it appropriate to use psychotherapy?

  Lucy Chen: [00:14:42] When thinking about when to employ psychotherapy. Clinicians need to think broadly and consider firstly the availability of the therapy, but also the provider and the patient's presentation. Let's see what Dr. Kennedy had to say.

  Dr. Sid Kennedy: [00:14:56] Well, I think there's a very good section in the 2016 guidelines written by my colleague Professor Perich, where the question of who gets psychotherapy is really. Raised. And so the first question is about availability of the treatment, because it's all very well to recommend cognitive behavioural therapy, but if nobody is trained to deliver it, that's a bit of an issue. Secondly, what is the patient preference? And many people have said I would like cognitive therapy, but I actually think the medication treatment might work more quickly, for example. So you have to look at issues of how much time have you got in reviewing that area. One of the issues that was the best predictor of response to a psychotherapy was the connection between the patient and the therapist, irrespective of what the modality of psychotherapy was. So these are the kind of non-specific issues.

  Lucy Chen: [00:16:02] We'll explain CBT a little later in the episode. But here Dr. Kennedy emphasise the importance of knowing who the therapist is and what kind of therapy is offered before contemplating the option of psychotherapy. In addition to access, we also need to think about the quality of the therapy. There are many people who can get training and deliver psychotherapy like psychiatrists, psychologists, nurse practitioners, but it should be delivered with sufficient time and quality. Dr. Kennedy mentioned a very interesting point that the best predictor of response to psychotherapy is the connection and rapport between the patient and the therapist. This is also known as a therapeutic alliance, highlighting again the importance of quality of delivery of therapy. The therapist should have the capacity and skills to engage the patient. Elaborating on the point of patient preference, we need to think about how interested the patient is in talk therapy. If they're disengaged and not interested, then psychotherapy is not likely to be fruitful. In addition, there's a certain level of understanding and capacity that the patient should have to process the exchange that happens in psychotherapy. If they're confused, delirious, or cognitively impaired, it could be hard to participate. Also, it's imperative to think about the severity of the depression. If a patient is presenting as severely depressed with poor concentration, lethargy and evolution, it could be difficult to engage them psychotherapeutic. As Dr. Kennedy mentioned, timing is also an important consideration. The efficiency and speed of medication may serve as a more appropriate choice for therapy until the patient has a more severe episode. It would also be unwise to recommend monotherapy with psychotherapy in a severely suicidal patient or patient with psychotic depression. In this case, stabilisation with medication , ECT would be much more appropriate as a first choice.

  Alex Raben: [00:18:02] That makes a lot of sense, Lucy. Now, I'm wondering how this relates to pharmacological treatment of depression. Is it more effective to have both medication and psychotherapy? Do we start them together or one after the other?

  Lucy Chen: [00:18:15] That's a great question and one that I asked Dr. Kennedy myself.

  Dr. Sid Kennedy: [00:18:19] So you've asked about when would you start two therapies at the beginning or even later on versus one. And the truth is that most of the studies look at treatments in a sequential way, although there's a small literature, particularly in medications, that has looked at the idea of starting two treatments right from the beginning. And I think from the psychotherapy point of view, people who've had recurrent episodes or perhaps have a chronic depression, then the combination of, say, cognitive therapy with an antidepressant might be particularly helpful. And an interesting evidence to support. That was a study done at least a decade ago where a drug that we don't use anymore called Nefasedone or Searson was actually used with a modified version of cognitive therapy. It was actually called cognitive Behavioural analysis System Psychotherapy or C bass. So you can remember by the fish. Now, what happened there was interesting that the combination of treatment was better than either alone for people who had chronic depression. On the other hand, if you looked specifically at the question of early childhood trauma, those people who had early childhood trauma did better when they got the psychotherapy either alone or with the drug, and they did less well with the drug alone. So, again, it's telling you how certain variables with an individual patient might influence the treatment choice.

  Lucy Chen: [00:20:08] Combination treatment for a major depressive disorder can be employed either sequentially, as in medication followed by psychotherapy or vice versa or concurrently. So basically starting both treatments at the same time. With regards to sequential treatment, you can think about adding psychotherapy. If somebody has a partial response to an antidepressant, it may be useful to add psychotherapy. In this case as an adjunctive treatment. It's been hard to evaluate the outcomes of combination therapy because of the varying modes of delivery. But Dr. Kennedy has suggested that some studies have revealed that combination therapy with an anti depressant and psychotherapy at the same time has been of benefit in chronic depression. There was also a meta analysis conducted in 2009, combining 18 studies with over 1800 subjects that concluded that concurrent medication and psychotherapy was superior to psychotherapy alone, with a small to moderate effect. Size of 0.35. Interestingly, when concurrent therapy is evaluated in more focal populations like the elderly, its superiority increases. This further highlights Dr. Kennedy's point that certain variables within a patient might influence the treatment choice and its effectiveness.

  Alex Raben: [00:21:28] I think a lot of us have heard about CBT or cognitive behavioural therapy, but could you explain this further? Lucy and when you might use it?

  Lucy Chen: [00:21:36] Sure. So CBT cognitive behavioural therapy is a standardised form of therapy that aims to correct cognitive distortions. So basically cognitive distortions are ways that we convince ourselves is something that really isn't true. These inaccurate thoughts usually reinforce negative thinking. For instance, Aaron might get upset over the fact that a colleague at work made a joke about her when she accidentally pressed a few extra buttons on the photocopy machine and made 100 copies of a patient document instead of just one. Suddenly she feels incredibly stupid and embarrassed and is flooded with negative feelings about herself. But look, looking at the big picture, the joke by her colleague could have also been an attempt to make light of the situation. Or perhaps this is a colleague who always makes jokes to try and get attention. By reinterpreting the intention of the joke and the situation, the patient may feel less poorly about themselves. So CBT uses logical analysis to break down these automatic negative thoughts and reinterpret them to elicit more realistic, healthy emotions and behaviour. So CBT can be done in groups or on a 1 to 1 basis. Either way, the sessions typically occur once a week for about 15 weeks. The skills required to perform to perform CBT can be required through a CME workshop or by collaborating with a psychiatrist.

  Alex Raben: [00:23:01] Great. Thanks Lucy. That was an excellent introduction to CBT. Can you tell us a little bit about the other psychotherapies that we might consider in Erin's case?

  Lucy Chen: [00:23:11] Sure. Let's turn to our expert for that answer.

  Dr. Sid Kennedy: [00:23:14] The evidence base for cognitive behavioural therapy is level one, first line treatment, level one, evidence, interpersonal therapy or interpersonal psychotherapy. IPT  would have the same level of evidence. The difference in the 2016 is that mindfulness based cognitive therapy would now be seen as having level one evidence as a maintenance treatment beyond the acute stage, but level two evidence as an acute treatment. So we have three psychotherapies that would certainly be competitive with any of the drug treatments. And there have been a large number of meta analyses looking at cognitive therapy in particular compared to pharmacotherapy and with the exception of people who have psychotic symptoms who are in acute suicidal risk in general, if you have optimal psychotherapy, cognitive therapy, the outcomes can be as good as pharmacotherapy, but the availability also is a problem.

  Lucy Chen: [00:24:32] So in terms of first line treatments, it seems that CBT, IPT and NBCT are considered to be the most recommended so and NBCT is another form of cognitive behavioural therapy and it stands for mindfulness based cognitive therapy. Dr. Kennedy mentioned BCT as having level one evidence for maintenance therapy, but level two evidence for acute therapy, which makes sense because NBCT is designed to really help people suffer through repeated bouts of depression and chronic unhappiness. NBCT uses traditional CBT methods and as this extra dimension of mindfulness and mindfulness meditation. And this is really a focus on awareness of all incoming thoughts and feelings and accepting them, but not attaching or reacting to them. This process is known as de centring and AIDS in disengaging from self criticism, rumination and dysphoric mood that can arise when reacting to negative thinking patterns. Like CBT and NCBT, it functions on the theory that individuals who have depression have negative cognitive distortions that trigger a depressive episode. However, instead of reinterpreting them, the goal of NCBT  is to interrupt these automatic processes and teach the patient to focus less on reacting to incoming stimuli and instead accepting and observing them without judgement. NC is more so for treating the maintenance phase of depression as highlighted by Dr. Kennedy. And currently, Erin is suffering in an acute phase. So this really isn't the best option to start her off with. Ipt Interpersonal therapy is a problem focussed treatment for depression and this approach, the focus of therapy, is on current relationships and interpersonal events that contribute to the onset and or maintenance of depression. Ipt focuses on a key issue and one of the three problem areas. So one is recent life changes or transitions like a divorce, marriage, moving job loss, two conflicts with others. Three Grief related to loss of a significant other. Ipt helps to reduce distress through understanding and improving relationships at work, home and social life. Adjusting to life changes and building relationship skills.

  Alex Raben: [00:27:00] Great. Thanks, Lucy. So let's put this all together in the context of Erin's case now. She has a mild depression and is quite high functioning. Based on that, you propose psychotherapy as a monotherapy. Given that she seems to have a number of negative cognitive distortions and has not really been focusing on the recent Break-Up with her ex boyfriend, you decide to recommend CBT over IPT, You realise NCBT would also not be indicated in Erin's case because she's in the acute phase of illness. Erin has heard about CBT before and is interested in trying it, but she would like to join a group therapy session that is covered by the government. You explain to her the CBT groups available in your area. However, there is a substantial wait time. Erin agrees to be put on the waitlist for these groups, but asks you if she could try a medication in the meantime, as she wants to get better as quickly as possible. She asks how quickly she can expect to feel better on the medications and what side effects she might expect.

  Carrol Zhou: [00:28:17] So today, let's talk about four general classes of antidepressants which make up the first line treatments. The first is selective serotonin reuptake inhibitors or SSRIs. That's things like fluoxetine, sertraline, citalopram and escitalopram. Yes. Then we have the serotonin, norepinephrine, reuptake inhibitors or snris, like venlafaxine and duloxetine, for sure. And finally, we have norepinephrine, dopamine reuptake inhibitors or NDRI, which is bupropion and noreadrenergic and specific serotonin agonists or NASSA which is Mirtazapine. Wow. That's a lot of classes of medications. So to summarise, we have SSRIs like fluoxetine, SNRI  like venlafaxine and then bupropion and Mirtazapine are on in their own classes. Now how would you choose between all these options?

  Carrol Zhou: [00:29:18] Well, like I said, these are all first line, so one isn't necessarily better than the other for treating symptoms of depression. We often end up choosing them based on the differences in their side effect profiles. Side effects.

  Lucy Chen: [00:29:31] Maybe you can tell us a bit more about how you would counsel patients who are about to start an antidepressant.

  Carrol Zhou: [00:29:36] Sure. So side effects generally fall into two categories. One is serious but uncommon, and the other is non life threatening, but very common side effects. There are very unique side effects associated with each class of medications. And again, for the sake of our brain capacities, I think it may be just wise to talk about SSRIs for today so we can walk away feeling comfortable with prescribing one class of antidepressants. So the serious and life threatening but very uncommon things can include number one, serotonin syndrome.

  Carrol Zhou: [00:30:13] It's a cluster of life threatening symptoms that's caused by significantly elevated levels of serotonin in our system. This can happen to individuals taking SSRIs, but it occurs usually only if they're co prescribed with other serotonergic agents. And frequently it happens when you take SSRIs and another class of antidepressants called MAOI or monoamine oxidase inhibitors. Those are not first line treatments for depression. The key here, though, is to always use a drug interaction checker app when you're prescribing antidepressants to make sure that other medications are not synergistically increasing your systemic serotonin in some way. So the second adverse effect to know about is suicidality associated with SSRIs. I think it's at this point important to define what suicidality means. And it can be done in two ways as either completed suicides or suicidal thoughts and behaviours. And we need to know how SSRIs can affect each of these definitions. So basically SSRIs do not increase the risk of completed suicides in adults or children. But research on suicidal thoughts and behaviours is more controversial. This is due to the fact that the physical symptoms of depression often improves before the cognitive and mood symptoms, so people find themselves feeling more restless, yet their mood is still bad. Age seems to be a protective factor, with older individuals being less likely to develop increased suicidal thoughts and behaviours. But studies have shown that there is an increase in those thoughts and behaviours in children and in some studies young adults age 18 to 24 years.

  Carrol Zhou: [00:32:02] Although I should add that for those young adults the data did not reach statistical significance. Nevertheless, there is a black box warning for most SSRIs for children and adolescents with the age limit extended to include young adults.

  Lucy Chen: [00:32:17] To summarise, beware of serotonin syndrome when prescribing SSRI. As with other serotonergic medications. Also, SSRI can be associated with increased suicidal thought behaviour, especially in children and possibly young adults. But what about some non-serious side effects?

  Carrol Zhou: [00:32:36] There are a lot of common side effects and I will again only touch on the big ones. And for the SSRIs, the reasons SSRIs make us feel better theoretically, is because the increased concentrations of serotonin will bind to a specific subset of serotonin receptors called 5HT1A receptors which are linked to mood. Unlucky for us, though, there are other 5HT receptors in our central nervous system that does not regulate mood, which causes side effects corresponding to increased serotonin levels in their synaptic clefts. For example, the synapses containing 5HT2A receptors are linked to sexual dysfunction. The synopsis containing 5HT2C receptors are linked to insomnia and anorexia, and the synapses containing 5HT3A receptors are linked to increased nausea and vomiting.

  Lucy Chen: [00:33:28] So seems like the more prevalent. But non-life threatening of the symptoms include sexual dysfunction, anorexia and GI upset.

  Carrol Zhou: [00:33:36] Precisely.

  Lucy Chen: [00:33:38] But what if someone experiences these common and bothersome side effects? But and then based on that, they decide to just stop the medications cold turkey?

  Carrol Zhou: [00:33:49] I think that's a very good question. It's important to remember that abrupt discontinuation dose reduction and tapering of antidepressants can cause withdrawal symptoms in SSRIs. The biggest culprit for withdrawal symptoms is paroxetine. And the withdrawal symptoms can look like any or all of the following. So some dizziness, nausea, vomiting, chills, insomnia, or even electric shock like sensations down one's back. Visual phenomena, anxiety, agitation. There have even been cases of post discontinuation mania that's been reported.

  Lucy Chen: [00:34:27] So based on these side effects, it seems like it'd be important to counsel these patients on not abruptly stopping their medications once you start them so they can avoid these side effects. 

  Carrol Zhou: [00:34:37] For sure.

  Lucy Chen: [00:34:39] Okay. So out of curiosity and we don't have to go to much detail here, but what are some of the indications for using some of the other classes of medications like you mentioned before, like Buproprion and Mirtazapine? Just so our listeners get a flavour for them, get an idea of their clinical utility for sure. So, so to be really brief and again, it's not an inclusive list at all, Buproprion and Mirtazapine generally have less sexual side effects than the other antidepressants. So if someone's really worried about that, it's good to introduce them to these options. However Buproprion, needs to be used with caution and individuals with seizure disorders because it may lower the seizures threshold. So that's something to be aware of. It can also be what we call activating, which means inducing increased anxiety and insomnia. So it's not good for someone who already has issues with that.

  Carrol Zhou: [00:35:33] Mirtazapine, on the other hand, tends to be more helpful with sleep. It also comes in a sublingual formulation, so it's helpful for people that have difficulty swallowing, but it can also cause weight gain.

  Lucy Chen: [00:35:46] Thanks for touching on those two classes or those two medications Carol. Also, Aaron was wondering how long it takes for these anti depressants to work and what should we tell her?

  Carrol Zhou: [00:35:57] It generally takes about 2 to 4 weeks or longer for the therapeutic effects of antidepressants to kick in, especially the mood and cognitive symptoms, whereas physical symptoms such as sleep or low energy may be improved earlier on in the treatment course as early as 1 to 2 weeks. It's really important for us to learn the side effect profile and time lag for antidepressants to start working and to educate the patients on how long it's recommended also to continue medication even after they start feeling better. If people are not informed of this, this can contribute to them not being adherent to the treatment. For example, statistics show that 30% of patients discontinue within 40 days of starting an end depressant and more than 40% discontinue within 90 days. So this is a huge problem with antidepressants. 

  Lucy Chen: [00:36:49] For sure. Now I really see the value of counselling. But in what ways? Like how would we measure the level of improvement in patients?

  Carrol Zhou: [00:36:58] Yes, this is another very clinically relevant question. We need to use validated scales consistently to measure the change in her symptoms instead of just having a general clinical impression every time we see her. There's lots of research to support this, and the CANMAT strongly recommends this as well.

  Lucy Chen: [00:37:17] But what if a patient is on a therapeutic dose of an antidepressant? They stay on it for 2 to 4 weeks, but then they don't get a response. Like, what do we do then?

  Carrol Zhou: [00:37:27] Right. So there are generally three things you can do when there is no response or only partial response. They are one, optimising the dosage. Two, augmenting or combining with a different medication or three switching to a different class of medication completely. So optimising just means making sure that the dosage that the patient is on is therapeutic. Augmenting means we're adding a new medication that's not classically considered to be an antidepressant in order to improve the antidepressants efficacy. Combining means adding another antidepressant switching just means discontinuing or tapering off of what you currently are on and then starting a whole new different medication altogether.

  Lucy Chen: [00:38:14] So it seems like if something's not working, we have a few options, one of them being optimising the dosage, another one being augmenting or combined with another antidepressant or completely switching to a different depressant. Cool. When would I do each of these things?

  Carrol Zhou: [00:38:32] The CANMAT provides a really great diagram to try to tackle this issue in a systematic and algorithmic way. So basically, after four weeks of antidepressant therapy, a few things can happen. Either you, a improve and go into full remission, which is what we all hope for, or b you improve, but only partially by as evident by a validated depression scale. And three, the patient does not improve at all, or they're just totally intolerant physically to the treatment.

  Lucy Chen: [00:39:08] So if the patient goes into remission, you know, it's intuitive for them to stay on this medication. But if they don't improve or they can't tolerate the treatment, they can clearly be switched.

  Carrol Zhou: [00:39:20] Yeah, that's right.

  Lucy Chen: [00:39:22] But what if they they don't completely improve. They only partially improved the medication.

  Carrol Zhou: [00:39:28] Right. So that's the time that we would consider either augmenting or combining the existent therapies with another medication, because residual depressive symptom is a risk factor for relapse into another major depressive episode. Our goal of treatment is always for the patient to achieve complete remission.

  Lucy Chen: [00:39:49] But what if augmenting, combining, doing all these things still doesn't work,

  Carrol Zhou: [00:39:54] Then it may be time to switch. We would taper the patient off of their current medication safely and then start them on a different class of medications. The Star D trial, which is the landmark trial that everyone sort of quotes in psychiatry, shows that 28% of individuals achieve complete remission with their first antidepressant and then 25 additional percent of patients achieve that with their second antidepressants. So 53% of patients should be expected to achieve full remission after two sequential treatments. And hopefully, in our case, Aaron falls into that group. But unfortunately, there's really no way to tell how she's going to respond to each kind of treatment.

  Dr. Sid Kennedy: [00:40:47] One of the most important comments of this, Discussion is that it would be very naive to think we have only one type of depression and only one dysregulated brain mechanism so that everybody should naturally respond to the same treatment. It doesn't help. It doesn't happen with hypertension. It doesn't happen even with diabetes. Doesn't happen clearly with infections. So why should we expect that one treatment will help everybody with depression? So I think the problem sometimes is identifying who would the key responders be. And that's where the whole pursuit of biomarkers, where the whole question of better defining subpopulations within a group of depressed people might well help us to say you're the group who would do best with our teams. But there's another group over here who actually are excellent candidates for behavioural activation, and that's the that's the next challenge, I think.

  Lucy Chen: [00:41:51] I see. But how long should people go on antidepressants for?

  Carrol Zhou: [00:41:56] Yeah. So you can tell them that once they start getting better, if they're a low risk adult, generally, you put them on for 6 to 12 months after that. And if they have risk factors like older age or recurrent episodes or really severe disease, then we think about putting them on this medication anywhere from two years to longer.

  Lucy Chen: [00:42:19] All right. Thanks, Carol. So now I just want to kind of start applying some of this newfound knowledge of pharmaco pharmacology to Erin's case. So we discuss with Erin the common side effects, which include sexual dysfunction, GI, upset, insomnia and anorexia, as well as some of the more serious side effects such as serotonin syndrome and suicidality. We've explained to her that it will take about 2 to 4 weeks before she notices any changes to her actual mood. We explain that we'll make these recommendations to her family doctor and that this will be a one time consultation and that she'll need follow up with her family doctor regularly after starting the drug and should follow up sooner if she experiences any suicidal thoughts. But what drug will we actually recommend to her family? Doctor, to start with.

  Alex Raben: [00:43:13] If you were just starting an antidepressant and someone for the first time, which drug would you go with? I know that the 2009 guidelines point to some drugs having superior possible superiority. Does that come into play?

  Dr. Sid Kennedy: [00:43:26] So that's a good question. If we think about first drug selection or first antidepressant choice. There was a very influential meta analysis around 2009 that looked at both the dropout rate and the response rate across more than 12,000 people where there had been head to head  trials. The author was Cipriani. And what he showed was that if you took a composite of response and dropout, escitalopram and Sertraline looked better than the other agents. Now, there were limitations, of course, in that not all trials used the same measures. A dropout is a fairly crude measure of whether you tolerated a drug or you didn't. It only captured the, if you like, the tail end when we looked at this for the 2016 guidelines, we probably took a broader, slightly more conservative position and we recognised that there tended to be not so much difference across most of the current SSRI as entry agents. And in general, we didn't recommend one SSRI or snris over another.

  Lucy Chen: [00:44:49] So it seems like it's really about choosing the right drug for the patient. Aaron expresses a desire to minimise sexual side effects and also doesn't want to feel tired at work. So we recommend starting her on Buproprion, which she actually agrees with. So that covers the basics of pharmacology for depression. Let's switch gears now to neurostimulation therapies. Alex focuses his research on these therapies and can give us an overview.

  Alex Raben: [00:45:27] Thanks, Lucy. So again, I'll just cover the basics here. Neurostimulation therapies are therapies used in depression and other illnesses that apply electrical currents or magnetic fields to stimulate the brain. The one that our audience will most likely be familiar with is the tried and true electroconvulsive therapy or ECT.

  Lucy Chen: [00:45:54] Yeah, I've heard of ECT  and also I think most people are familiar with it in one clue. One Flew Over the Cuckoo's Nest, where they shock Jack Nicholson when he didn't behave. But what exactly is it?

  Alex Raben: [00:46:08] Yeah. I think it's good that you bring up One Flew Over the Cuckoo's Nest. Because it is. Depiction in many of our patients mind, and it's actually quite inaccurate. So in the movie, it's depicted as something that's involuntary, it's used as a punishment, but in reality, it's actually a very helpful therapy that doesn't involve a lot of these negative aspects.

  Lucy Chen: [00:46:34] Yeah, in the movie it seemed like it was really painful and highly debilitating, but what is ECT actually like in reality?

  Alex Raben: [00:46:43] So modern ECT involves anaesthesia and it involves muscle relaxants to prevent discomfort and to prevent seizure movements. So the patient doesn't actually feel anything that's happening. Once the patient is under anaesthesia, that's when the psychiatrist will apply the electrodes to the scalp and induce the seizure through the electrical current.

  Lucy Chen: [00:47:08] It seems like it's pretty much just like any other procedure, but it's still pretty involved. So why do we use it when we have antidepressants?

  Alex Raben: [00:47:19] It's a good question. And the reason is that it's highly effective. So response rates are between 80 and 90% in general, depressed patients and 50 to 60% will respond if they're treatment resistant. Nothing else in our armamentarium comes close to it in terms of effectiveness.

  Lucy Chen: [00:47:41] So it sounds like it works better than antidepressants. Now, kind of flipping my previous question, why do we use antidepressants instead of ECT?

  Alex Raben: [00:47:50] Yeah. So ECT is not perfect either. It comes with side effects and the most important being memory loss. This is the most common side effect of ECT, and it's both anterograde and retrograde. So both before and after the ECT treatment and it can be up to months before and after that the patient has trouble remembering or it's fuzzy for the patient. And patients will often complain about this after ECT. Because of this, ECT is generally reserved only for certain clinical situations. In the CANMAT guidelines, it's a first line treatment for life threatening depression, which includes depression with psychosis, severe suicidal ideation, or those depressed patients who are catatonic or unable to care for themselves. It is also used for depression resistant to other treatments, and for those patients who have done well on ECT or in the past or have a preference for trying ECT.

  Lucy Chen: [00:48:49] So ECT seems like a lost measure of sorts. It seems like it's a very safe therapy and actually our most effective treatment of depression and therefore is first line in really difficult cases despite the amnesia may cause. Do I have that right?

  Alex Raben: [00:49:05] Yeah, that's exactly it. ECT not the only available neurostimulation therapy, though. Nowadays we also have rTMS or repetitive transcranial magnetic stimulation. As the name suggests, it uses magnetic fields to induce electrical currents in the brain. The major difference here from ECT is that rTMS can target specific areas of the brain and therefore does not cause seizures or memory impairment. Unfortunately, another difference is that so far it has not proven to be as effective as ECT or other therapies for that matter, that are used for treatment resistant depression. The response rate is somewhere in the ballpark of 25 to 30% of patients. However, rTMS is growing every day. It's a hot area of research and so we may see changes in this area. It also has a relatively benign side effect profile, and so it's certainly a good option for the right patient. Again, CANMAT recommends it as a second line treatment for treatment resistant depression, and a more recent European guideline made similar recommendations. Finally, I should also mention deep brain stimulation as well as vagal nerve stimulation. However, these therapies are rarely used and are experimental, and so we won't go into detail here.

  Lucy Chen: [00:50:33] Cool. That's really exciting. It seems like there's a lot of growth happening in neurostimulation therapy and the research involved. Let's hear what Dr. Kennedy had to say about the future of neurostimulation in depression treatment.

  Dr. Sid Kennedy: [00:50:46] So what do we mean by neurostimulation treatments for a person with depression? 30 years ago, we talked about electroconvulsive therapy. If it was the media, you talked about shock therapy. You had Jack Nicholson and The Cuckoo's Nest, and you scared everybody away from the treatment. Today, we would say our rTMS transcranial magnetic stimulation is probably an entry level, if you like, to neurostimulation. It's a matter of choice. Some people would go there before they would have pharmacotherapy. Usually people have had some pharmacotherapy. They've become aware that rTMS is an available treatment and so they've stayed on the antidepressant and perhaps the rTMS has given them a boost. And I think about 50% of people who get rTMS do get a boost from the addition to existing pharmacotherapy. Many people do not respond and they either go back to pharmacotherapy or they begin to look at the two forms of seizure therapy. So electroconvulsive therapy or magnetic seizure therapy, ECT, ironically has a very robust evidence base of efficacy, but it also has a relatively high level of side effects, particularly the memory issues. And frankly, it has one of the worst public relations officers, I think, of any treatment. So it has a very bad public perception. Over the years I've had people come and say, Don't waste my time with other treatments I had ECT eight years ago. It worked very quickly and I was back at work in four weeks. That's all I want. Don't give me anything else, but that's the minority opinion. So ECT today may or may not require inpatient hospitalisation. It may be able to be given on an outpatient basis as long as there's somebody to accompany a person back home.

  Dr. Sid Kennedy: [00:53:04] And again, the evidence of efficacy is very good. Magnetic seizure therapy is an alternative that may have less side effects in terms of memory, still will require anaesthetic. And so many of the issues relate to recovery time from anaesthetic for for many patients. Now if we go and I should say that more recently, while rTMS has been an approved technique in Canada for a number of years, one of the limitations has been whether as a treatment service it's actually funded for physicians to build their health insurance scheme so that that has become a recognised billing code in Ontario quite recently. So the limitation of access, of course, remains an issue. You won't have trouble getting RTMs in Toronto, but you might have trouble in Oshawa or some smaller centre. So that's an issue there. Now the final neurostimulation treatment is deep brain stimulation treatment, which is undoubtedly the most invasive procedure in psychiatry. If you talk to a neurosurgeon, he or she would say, Well, it's a very specialised procedure, but it's not a very invasive procedure because we're not actually cutting any circuitry. We're inserting these fine wires under MRI guidance. And so this specificity and the reversibility of the treatment is quite remarkable. But that's an experimental treatment. We happen to have used it probably more times in Toronto for depression than anywhere else in the world. But it's far from an evidence based treatment at this stage. It's still an experimental treatment.

  Lucy Chen: [00:55:16] I see neurostimulation as something that's important to that's important to depression treatment, but likely will not be something that we would try right away with Aaron's case.

  Alex Raben: [00:55:26] Yeah, exactly.

  Lucy Chen: [00:55:28] Let's go back to Carol now and wrap up our treatment modalities with complementary and alternative medical treatments or CANMAT treatments.

  Carrol Zhou: [00:55:36] Sure. So essentially, in the 2009 guidelines, only one complementary and alternative sort of treatment has first line evidence, and that's light therapy for major depression with a seasonal pattern like therapy is basically daily exposure to bright light, either with a fluorescent light box or in some cases LEDs. I think it could be very helpful for people who don't want any therapy.

  Lucy Chen: [00:56:03] Wow. That's pretty interesting. How long does it usually take for it to work?

  Carrol Zhou: [00:56:07] The response usually occurs within 1 to 3 weeks.

  Lucy Chen: [00:56:11] Hmm. And are there any side effects of using a light box?

  Carrol Zhou: [00:56:15] Yeah. So with any intervention, there are potential side effects. For light therapy, these are usually mild and include headache, eye strain, nausea, agitation. But they really lead to people wanting to discontinue their treatments. However, one thing we have to be aware of is a serious adverse effect of triggering a hypomanic or manic episode in someone with a bipolar disorder. So therefore, it's really important to rule that out in your history, like we discussed in our first episode.

  Lucy Chen: [00:56:47] Mm hmm. So it was the light box only for depression with a seasonal affective pattern.

  Carrol Zhou: [00:56:53] Actually, since the publication of the CANMAT almost seven years ago, there has been lots of other studies that suggest that light therapy could work for depression without a seasonal pattern, either by itself or in combination with something like Sertraline as an antidepressant. The newest CANMAT guidelines in 2016 have reflected this change in level of evidence, as according to Dr. Kennedy.

  Lucy Chen: [00:57:20] That's interesting. It's really nice to know that there's alternatives to medications as well. But what about more kind of simple therapies, sort of like exercise and diet?

  Carrol Zhou: [00:57:30] Aside from light therapy for seasonal depression, there are no alternative therapies that are noted as first line. And this excludes exercise and dietary like nutraceuticals like omega three and folic acid. Given the poor level of evidence with potential benefits, how do you approach this topic with patients as a recommendation?

  Dr. Sid Kennedy: [00:57:54] Well, I think the key point is that we value the benefit of exercise, whether you're depressed or not. So if you are depressed, presumably we should value it even more. The problem I would have is to say when somebody would come in, I don't want to take any other treatment. I feel I can hardly get out of bed. I have suicidal thoughts, but I just want exercise. It's not a very practical and there's no evidence to say for a severe form of depression that that would be an adequate monotherapy. Most of the studies that have been done have actually been done in universities with college kids where the level of depression would be at best mild to moderate. And there's no doubt exercise is good. It's good for everybody. So you you find it hard to generalise. And one of the biggest issues when you look at complementary and alternative medicines in a guideline document compared to pharmacotherapy and magnetic stimulation is that it's almost certain the population studied differed quite significantly across these. So how do you apply the same standards? We try because we look for evidence of the severity of the disorder. Was there a structured clinical diagnosis even to start with? Because in some cases the CAMS have been used for depressive symptoms rather than syndromes. But I think that light exercise, folate and omega three are probably among the most robust in terms of being adjunctive treatments that could be recommended. Methyl folate, for example, had a number of studies that looked quite promising. And then in other cases, they were not replicated. So but that's no different than some pharmacotherapy, some drug treatments that you might get one promising, uh, trial. And then another one is less promising.

  Alex Raben: [01:00:22] Okay, now that we've gone through the various treatments, let's go back to Aaron's case. You inform Aaron of the importance of diet and exercise as contributing to an overall feeling of well-being and that these interventions can help her depressive symptoms in conjunction with her medication. After wishing her all the best, you go to speak to your family medicine colleague about your recommendations for Aaron, and he agrees with your plan and is happy to follow up with her. One month later, you run into the same family doctor and he gives you a brief update on Aaron. It seems as though she is tolerating the bupropion well and having been on this medication for months now, she's starting to feel like herself again. You are glad Aaron is doing better and that you were able to meaningfully contribute to her care. Thanks for listening to PsychEd. We hope that you enjoyed our second episode as we're new to this. We'd really appreciate your feedback. You can find us on Twitter at Psyched Podcast Or you can email us at info@Psychedpodcast.com This episode of Psyched was written and produced by Lucy Chen, Bruce Fage, Lu Gao, Alex Raben and Carrol Zhou. This podcast was made possible by the support from the Department of Psychiatry at the University of Toronto. We would like to especially thank Dr. Sid Kennedy, who took time out of his busy schedule to speak with us on the treatment of depression. We'd like to also thank Dr. Elise Hall, our staff psychiatrist editor. Thank you once again for listening.

Episode 1: Diagnosis of Depression with Dr. Ilana Shawn

• Episode 1: Diagnosis of Depression with Dr. Ilana Shawn

  Lucy Chen: [00:00:01] Okay, picture this. You've just arrived at the first day of your psychiatry rotation in clerkship or residency. You feel a twinge of excitement and fear because a part of you wonders if you have the knowledge and expertise to perform well here. You straighten your shirt, take a long sip of your coffee, and wait in anticipation for what's to come. Just then, your family practice colleague approaches you about one of their patients. The patient's name is Aaron. Hi. My name is Aaron. She's a 25 year old first year resident in internal medicine. She presented a few weeks ago with fatigue and feeling unable to keep up with her peers at work. She wonders if there's something physically wrong with her or she could be depressed. She mentions that three months ago she broke up with her long term boyfriend, which she proposes might be the cause of all of this. Your colleague feels that she likely is depressed, but is also wondering if this might be just a normal reaction to the loss of her boyfriend. Aaron is reluctant to accept the diagnosis of depression and realising there's a psychiatric expert on the team has requested your opinion. What do you do?

  Dr. Lu Gao: [00:01:20] Do we pronounce it psyched or psych ed?

  Dr. Alex Raben: [00:01:23] PsychEd.

  Dr. Lu Gao: [00:01:23] Okay. Got it. Got it. I see. I see. I see what's happening here.

  Dr. Alex Raben: [00:01:26] It's psychEd. Yes.

  Dr. Lu Gao: [00:01:29] You're listening to Psyched. The Educational Psychiatry podcast Made for Medical Learners by Medical Learners, where a group of first and second year residents at the University of Toronto in Canada who have come together to discuss important topics in psychiatry through our own research and with the help of our world class staff psychiatrists. I'm Lu Goa.

  Dr. Alex Raben: [00:01:48] I'm Alex Raben.

  Carrol Zhou: [00:01:50] I'm Carol Zhou.

  Lucy Chen: [00:01:51] And I'm Lucy Chen. And today's show, we'll tackle the basic criteria for diagnosing depression. Tips on history taking and what to look for on physical exam in investigations, diagnostic conundrums, important rule outs, all of which are revealed with our research and the help of our own hand expert, Dr. Ilana Shawn. We sat down with Carol, one of our first year residents, to iron out the intricacies of assessing for depression.

  Dr. Alex Raben: [00:02:18] But why is it so important for us to learn to assess for depression.

  Carrol Zhou: [00:02:23] Depression as a significant impact on society, both on an individual level as well as on a global scale? It has an impact on the individual themselves, on their relationships, as well as on someone's employment and work future. If you think about it, the onset of depression is often in the twenties, and that's the beginning of someone's productivity in terms of their life. That's when they're gaining skills, They're starting their employment future and they're working towards a certain trajectory. If someone becomes unwell at that point, that's very much going to impact their education, their future, career prospects and relationships. When I think about disease burden, we have to think not just about the prevalence of a disorder, but also the amount of time someone spends unwell, the lifetime prevalence of depression in Canada is somewhere around 10%. And if the average depressive episode is at least three months, you can imagine that's having a significant impact on a significant portion of the population. Depression can also be chronic at times, or at least it's an episodic illness. So individuals may have more than one episode in their life, which is going to impact them at additional times.

  Dr. Alex Raben: [00:03:36] A statistical measurement that's relevant to depression is called the DALY or disability adjusted life years. One value can be thought of as one lost year of healthy life. The sum of these years across the population can be thought of as a measurement of the gap between current health status and an ideal situation where the entire population lives to an advanced stage free of disease and disability. Using the DALY, unipolar major depression was classed in 1990 as the fourth leading cause of burden of disease worldwide for both sexes, just behind lower respiratory infections, diarrhoeal diseases and perinatal disorders. By 2004, it's now up to third place. The World Health Organization projects that it will be the leading cause of disease burden worldwide by 2030. There's clearly a need to explore and gain a better understanding of this highly debilitating illness. So now that we have a better understanding of the impact of depression, let's get back to Aaron. How do we begin to diagnose someone with depression?

  Lucy Chen: [00:04:42] The most common diagnostic guidebook for health care providers in North America is the Diagnostic and Statistical Manual of Mental Disorders, or DSM. The fifth edition DSM five was released in 2013 and is generally accepted today as the main method for diagnosis. So a little bit of a disclaimer here. Any attempt to manualize human experience is likely to result in controversy. Despite numerous limitations, the DSM is an attempt to standardise the language of mental health professionals so that a health care professional in Vancouver can communicate with a health care provider in Halifax in a meaningful way. Since we lack strong objective criteria for disorders, things like x-rays or blood tests we diagnose based on patient report and our own descriptive observations of behaviour. It's an admitted work in progress, though research is expanding. By now you would have heard of the mnemonic for DSM criteria of depression, MSIGECAPS. It stands for mood, sleep, interest, guilt, energy, concentration, appetite, psychomotor retardation, or agitation and suicide. So the a criteria for major depressive disorder has these nine different symptoms, and the individual must have at least five of these for a period of at least two weeks to make these nine criteria easier to remember. We can break them down into three groups. First, you have the core symptoms of depression M for mood and I for interest. This means that there is no clinical depression without persistently depressed mood or anhedonia. So these two questions combined can be used as a 32nd screening tool for depression when asking about mood. It can be helpful to ask them to rate their general mood on a scale of 1 to 10 where ten is normal.

  Lucy Chen: [00:06:34] For Anhadonia, you can start by asking about things they do for fun or used to do for fun and lead it into asking if those hobbies or anything else still brings them pleasure or joy.

  Lucy Chen: [00:06:46] Second, there are the neuro vegetative symptoms. As for sleep. A for appetite and E for energy. In general, people describe a decrease in these functions, and it can be helpful to quantify the change. The classical sleep symptom is early morning awakening, but any form of disturbed sleep can be seen. Poor appetite can manifest in significant weight loss and reduced energy can be tied to anhedonia. With that said, the sleep and appetite criteria can also be filled if the patient describes an abnormal increase termed hyperphagia and hypersomnia. Lastly, there are the cognitive symptoms. C for poor concentration or indecisiveness? G For guilt or worthlessness, you can assess for concentration when asking about interests. Can you follow what's happening on a TV show?or do you have to read a page over and over again? In depression, people can lose their self-worth and thus confidence. And this can manifest in avoidance of going to school, work or even household chores. Guilt often appears as an exaggeration of a past misdeed, actual or imagined. Probably the trickiest question will be around suicide. A common worry is could I make a patient more suicidal by bringing it up so it's okay. And it's actually beneficial to ask patients about suicide even if they don't mention it. P is for psychomotor retardation or infrequently agitation. This is the part of the mental state exam. Other findings are often related to the other symptoms of depression.

  Carrol Zhou: [00:08:34] The next question is how do you ask these questions without sounding like a checklist?

  Dr. Ilana Shawn : [00:08:38] I think it's a really good question. Part of the psychiatric residency training is learning to be a skilled interviewer. We don't have CT scans or blood tests to diagnose our illnesses, so we need to learn to be as skilled as we can in interviewing, assessment and diagnosis. During an assessment. There's a conflict between doing a routine checklist and trying to understand this individual's experience and the impact it has on them. I try to balance open and closed-ended questions, so an open-ended question would be something that you can't answer with a yes or no. I will use a closed-ended question at the beginning of the screen and then I will open up more into open-ended questions to learn more. I will ask questions like. Tell me about your mood. Getting them to tell me in their own words how they might describe it. Tell me about your sleep. Tell me about your appetite. This allows the individual to really tell you what it's been like for them. I balance this out also with empathic and validating statements. This helps to build rapport with the individual, so ideally they feel heard and understood. And then I'll pepper that with summarising statement to just recap what we've covered. So what you're telling me is that for the past few months your mood has been terrible. You've been crying more, you can't get out of bed. You try and sleep, but you can't sleep.

  Dr. Ilana Shawn : [00:10:01] You feel totally dragged down in the daytime. You can't concentrate, and you just don't feel like yourself. That helps the person understand that you're on the same page and they can also correct you if what you understand to be going on is not their experience at all.

  Carrol Zhou: [00:10:38] Okay. The next question is about talking about the interview. What else should medical students or residents know?

  Dr. Ilana Shawn : [00:10:44] I think one thing to impart on people is to enter the interview with an open stance without expectation, trying to retain a non-judgmental place. The more that the person feels heard and understood, the more they're going to feel able to tell you. There is a balance between being patient-centred and being a diagnostician, and so that's where open-ended questions can enter in. And some of the other techniques I spoke about before. So when you start open-ended, then you still may need to get into specifics and I'll tell the person now I'm going to ask some very specific questions. You said your sleep is poor. What time do you go to bed? What time do you fall asleep? What time do you wake up? Really trying to get at the specifics because we then use that as we're treating the person to get a better sense of what's improving and what still needs ongoing treatment. Remembering Part of our job is to engage the individual and help them feel heard and understood. And then it's also to ensure that we're doing a thorough and accurate diagnostic assessment.

  Dr. Lu Gao: [00:11:45] Now, let's go back to Aaron's case. Take a moment and think about what kinds of questions you would ask for on your interview. Pause the podcast and write your questions down or think of some in your head.

  Dr. Ilana Shawn : [00:12:06] Here's Dr. Shawn's response there in this case.

  Dr. Ilana Shawn : [00:12:09] Firstly, I just want to say, in general, I sometimes think that people in the medical profession will get worse care because we don't do as thorough assessments as we should. We can often assume certain things because we feel we have a certain relationship with the patient from the get go or because we feel like they would obviously tell us. It's really important to do as thorough a diagnostic assessment as you would with anyone else, knowing that in some ways that might be frustrating, in another way that might be really appreciated by the patient. In terms of history, I would do the same thing. I always do assess for symptoms of depression and then symptoms of mania or hypomanic episodes. When I think about comorbid conditions. Definitely anxiety needs to be assessed both because it can be highly comorbid with depression as well as because anxious symptoms can be part of the depressive illness. We would want to think about other conditions that may also be associated like eating disorders. We know that individuals with eating disorders are going to be more likely to experience episodes of depression and also that, again, symptoms of poor appetite or disordered eating may be more common in depression. It can be uncomfortable to do a substance use history, especially on someone that you might feel a different relationship with. At the same time, this is very important. Substance use can be highly associated with mood disorders or may precipitate or worsen than them. You want to think about both illegal drugs as well as over-the-counter medications or prescribed medications.

  Dr. Lu Gao: [00:13:45] How was your list of questions compared to hers? Was there anything you may have missed? Let's see what Erin tells you.

  Erin: [00:13:53] It started about two months ago. I get tired and sad at the end of the day. I didn't want to do anything at all except eat and sleep. I thought it was just missing my ex. But nowadays I feel terrible. I can barely get out of bed and concentrating at work is impossible. I used to love seeing my patients, but now I don't think I'll ever be a doctor. I can't handle the stress and the sadness. I feel like I'm at the end of my rope. I mean, I don't want to die. I'd never kill myself, but I just don't see any hope for the future.

  Dr. Alex Raben: [00:14:32] In addition to the history, you notice that although Erin is well dressed and has impeccable hygiene, her affect is sad and at points tearful what might be called dysthymic. And she has barely looked up throughout the interview. She has also repeatedly put herself down during the interview and seems fixated on her failures. So this is depression. Problem solved, right? Not quite.

  Carrol Zhou: [00:15:00] When we think about conditions mimicking depression, we have to think about both conditions that may look like depression and are actually something else, as well as conditions that are associated with depression. Conditions that may mimic depression may be medical conditions like hypothyroidism, multiple sclerosis, obstructive sleep apnoea, all of which may have some similar symptoms or may actually even present as seeming to be depression. There are other conditions, such as in substance use, stimulant withdrawal. Individuals who are using either cocaine or amphetamine can look as if they're depressed when they're in withdrawal. But obviously, if you were to follow that along and get a good substance history, you may start to wonder about other factors or other diagnoses. Additionally, depression could be associated with either a unipolar illness or a bipolar illness and doing a very good assessment of bipolar affective disorder and manic or hypomanic state is going to be very important.

  Lucy Chen: [00:15:57] So Erin might be depressed or her low mood may be caused by another disorder or simply a part of normal human experience. We can rule out alternative diagnoses by doing a thorough psychiatric history, which always includes screening for psychosis, anxiety, drug use, current medications, and a past medical history in addition to mood symptoms. Let's look at the differential for depression that Dr. Shawn has laid out in more detail by breaking it down into categories. The main categories are primary psychiatric disorders, including other primary depressive disorders, depressive disorders due to another medical condition, substance or medication induced depressive disorder or normal human emotion and reactions such as grief and bereavement. Let's start by going through the other primary psychiatric disorders, which can be confused as depression.

  Lucy Chen: [00:16:51] Of all these disorders. As Dr. Sean mentioned, the most important rule out is bipolar affective disorder or BAD because it requires treatment with mood stabilisers rather than just antidepressants. You may be seeing a patient with bipolar disorder and a depressed episode, and this could be mistaken for unipolar depression if you don't screen for manic and hypomanic episodes in the past. For this reason, the DSM five makes it clear that if a patient has had a manic or hypomanic episode in the past, that was not the result of medication or medical illness, then the more appropriate diagnosis is bipolar in a depressive episode rather than major depressive disorder.

  Dr. Lu Gao: [00:17:35] Another primary psychiatric disorder that can be mistaken for depression is adjustment disorder with depressed mood. Difference here is that in adjustment disorder, feelings of low mood and hopelessness will follow a recent stressor and be relieved soon after the stressor resolves. On top of this, the patient will not meet enough MSIGECAPS criteria to be diagnosed with depression. Of course, other depressive disorders will also appear similar to depression. One of these is persistent depressive disorder, or PDD, which was formerly known as dysthymia. A simple way to differentiate between these two disorders. To think of PDD as a milder form of depression that lasts longer, specifically two years or more.

  Dr. Alex Raben: [00:18:16] Okay, Let's move on to medical causes of depression. It's difficult to sort out whether or not a disease causes depression. One of the reasons is that depression predisposes patients to developing certain diseases so they'll be more associated. Another reason is that medical illness can cause depression through psychosocial pathways rather than biological mechanisms. That said, there are certain conditions that are generally thought to cause depression through pathophysiological mechanisms. Some of the big ones to consider are neurological conditions, namely stroke, Parkinson's disease, multiple sclerosis and epilepsy. They can also be caused by endocrine disorders. The big ones here are hypothyroidism, Cushing's, Addison's and Hyperlipidaemia. Autoimmune conditions, namely lupus and sleep disorders, namely obstructive sleep apnoea, have also been linked to depression. If the depressive syndrome is truly secondary to an illness, it may be possible to reverse it by treating the underlying condition. When considering depressive syndromes that may be secondary to medical conditions, ordering investigations can also be useful for our assessment.

  Dr. Ilana Shawn : [00:19:34] The past medical history might give some information, as well as the constellation of medical symptoms that are generally not explained completely by major depression. A lot of people with major depression may present with somatic symptoms, and in fact, that can be a very common presentation and family practice settings. You want to think about things like family history of a certain medical disorder or having received treatment for a medical disorder in the past and not showing improvement. That would make me think more likely about a depression. Each specific medical disorder has its own constellation of symptoms, of course, so if someone's presenting with profoundly low energy, they're losing their hair, they're cold all the time. Maybe you want to think about investigating for hypothyroidism. Major depression is a diagnosis of exclusion, after all, and medical disorders may be contributory or the etiology of the symptoms. And we need to make sure that we rule these out with investigations.

  Dr. Ilana Shawn : [00:20:45] For a well, adult. Generally, the rule is you want to order tests with a specific diagnosis in mind for the example before with hypothyroidism, if the person's presenting with the complaints that we discussed about, that would be a good time to order a TSH. I might order a CBC if an individual is describing profoundly low energy, has had a history of anaemia, maybe also thinking about B12 or folate. If a person has a certain body habitus or tells you about headache in the morning, dry mouth, a history of snoring and maybe apnoea periods that their partner have identified, obviously then you want to think about ordering a sleep study and baseline electrolyte panel to ensure that there are no electrolyte abnormalities.

  Dr. Alex Raben: [00:21:28] So to summarise, Dr. Shwan, the basic investigations include CBC Electrolytes, TSH, B12 and Folate, and you can also add a number of other investigations if you have other conditions in mind.

  Lucy Chen: [00:21:44] Recreational drug use can also lead to depressive syndromes. A complete psychiatric assessment always screens for recreational drug use, and so this is when you will pick it up.

  Dr. Ilana Shawn : [00:21:55] Diagnosing depression in the context of a substance use disorder, what you want to think about is are these symptoms persistent even when the person is not using the substances or are the symptoms significant enough even in the context of the substance use that we can't fully explain them just by virtue of the substance use? In part, we also have to think about the specific substances and the effects those may have on the person, both in terms of intoxication and withdrawal. Certain symptoms are more likely to cause symptoms that may appear like a depressive disorder. As I discussed previously, in terms of amphetamine withdrawal.

  Lucy Chen: [00:22:30] Some of the most common substances that cause the depressive symptoms are alcohol as well as cocaine or stimulant withdrawal. If depressive symptoms only occurred in the context of alcohol use, then the correct diagnosis is alcohol induced depressive disorder. In terms of prescription medication. The list of prescription drugs which can cause depressive syndromes varies from textbook to textbook, and a long list can be found in the DSM five. Overall, the literature in this area is not great, but there are few drugs worth mentioning. Antiviral therapies such as interferon, used mainly for hep C and Atripla use for HIV corticosteroids and Alpha- Two adrenergic agonists such as clonidine and methyl dopa have all been shown to cause depressive symptoms. The heavy duty acne medication isotretinoin and the nicotine anti craving medication Varenicline have mixed evidence, with some trials showing an effect and others not. And although classically thought to recent literature suggests that oral contraceptives and beta blockers are not related to depressive symptoms. Finally, it is important to not mistake normal human emotion, just as grief, sadness and bereavement for depression. Some of the differences from depression are that grief and bereavement often come in waves, and the sadness griever has experienced remains in the context of the loss. Patients who are grieving also won't experience the guilt, hopelessness and worthlessness that often comes with depression. If guilt is present, it will again be in the context of some perceived failure in regards to the lost loved one or other life changing situation.

  Dr. Ilana Shawn : [00:24:20] There is a tension between overdiagnosis and under diagnosis. We don't want to pathologize what is real human experience. Part of being human is having feelings, and within the diagnosis of depression and the treatment, the goal is not to take away feelings. The goal is to treat the symptoms of depression. So how do we decide what is pathologic and what's a major depressive episode and what is just part of the normal human experience? The major thing we want to look at is the impact on someone's functioning. If you think about having a profound stress like losing your partner, I think it's understandable that you may have sleep loss and appetite loss. Of course, you would feel sad. You may have difficulties with concentration and may even think about if life is worth living. Where you have to think about is can the person regain their functioning? Can they return to work? Can they still have fulfilling relationships and over time learn to enjoy things despite the loss? That's a really important discerning factor that may help us decide if this is a major depressive episode or if this is part of the normal human experience.

  Dr. Lu Gao: [00:25:29] So how can we best help Erin? What's the evidence behind each treatment? And is there an algorithm? Find out next time on site where we discuss the various treatment modalities for depression.

  Dr. Alex Raben: [00:25:42] This episode of Psych was written and produced by doctors Lucy Chen, Bruce Fage, Alex Raben and Lu Gao, and Carol Zhou. This podcast was made possible by the support from the Department of Psychiatry at the University of Toronto. We'd like to especially thank Dr. Ilana Shwan. Just took a lot of time out of her busy schedule to help prepare for the interview and help us work on the script. Special thanks to our colleagues Dr. Mohamed Attia, Ruxandria Besanu and Candice Kung for their generous contribution and ideas in recording equipment.

  Lucy Chen: [00:26:19] Thanks for listening.

  Dr. Alex Raben: [00:26:23] Concert.

  Lucy Chen: [00:26:25] That's awesome. That's great.

  Dr. Lu Gao: [00:26:27] Psyched.

  Lucy Chen: [00:26:28] You just got signed. Are you psyched for the next one? I'm totally psyched for the next episode.

  Dr. Lu Gao: [00:26:35] Yeah, we'll figure that one.

  Lucy Chen: [00:26:36] Yeah, well, we'll figure it out. Okay. See you next time.