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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.