Episode 34: Ketamine for Treatment-Resistant Depression with Dr. Sandhya Prashad

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    Hi guys, welcome to PsychEd, the psychiatry podcast for medical learners by medical learners. In this episode, we hope to give a whirlwind introduction to the use of ketamine within psychiatry. Today, we will be discussing the topic with Dr. Sandhya Prashad.

    Dr. Prashad is a psychiatrist and is the founder and medical director of Houston Ketamine Therapeutics. She has extensive expertise using ketamine and is one of the most experienced ketamine psychiatrists in the US. Her clinical practice focuses on treatment-resistant depression and also incorporates RTMS, sometimes in conjunction with ketamine. Dr. Prashad completed both medical school and residency training at Baylor College of Medicine in Houston, Texas. She is a founding member and current president of the American Society of Ketamine Physicians, which is a nonprofit organization created to advocate for the safe use of ketamine for mental illness and pain disorders and to expand access to ketamine therapy. I am Chase Thompson, PGY 3 at the University of Toronto and I'll be hosting this episode.

    I'm joined by my colleagues who will be co-hosting. Today I'm joined by Dr. Nikhita Singhal.

    Hi, I'm Nikhita. I'm a PGY 2 psychiatry resident, also at the University of Toronto and very excited to be co-hosting today's episode.

    And we're also joined by our co-host Jimmy Qian.

    Hi, everyone. My name is Jimmy Qian. I'm a MS2 at Stanford University and really happy to be here today.

    Great. And we also have our expert amongst us. So Dr. Prashad, do you want to briefly introduce yourself?

    Of course. I think thanks for having me on. I'm really excited to be here and to do this.

    I think you kind of touched on a lot of my background. About for the past four and a half years or so, I've been using IV ketamine in my practice. I first started using ketamine because I had a patient who was very treatment-resistant and actually quite suicidal.

    At that time, there was a lot of literature and talk coming out about the anti-suicidal effects of ketamine. That's kind of how we decided to treat him. It worked amazingly well and probably saved his life.

    About a year and a half ago, Sporvio, the nasal S-ketamine was FDA approved. That's something we use in the practice as well. That's a little overview about me.

    Our practice is focused only on treatment-resistant disorders, pretty much at this point, using ketamine as ketamine and TMS.

    Thanks so much. Maybe we'll jump over to discussing the learning objectives for this episode.

    Great.

    By the end of this episode, the listener will be able to, one, describe ketamine and how it came to be used in the field of psychiatry. Two, develop an appreciation for benefits and potential harms associated with ketamine and how this compares to other treatments for depression. And three, understand how ketamine fits into the treatment of depression and suicidality, patient characteristics to consider before initiation, potential mechanisms of action, different models of administration and incorporation of psychotherapy.

    Wonderful. So without further ado, we'll jump into things. So to start with, Dr. Prashad, could you tell us just a little bit about what ketamine is?

    Yeah, so ketamine is actually a synthetic molecule, but it was originally created for anesthesia and still used for anesthesia. It's been out for decades. We use it now a lot, mainly in children, to kind of reset bones and things like that in the ER.

    And it's what's considered a dissociative anesthetic. And we can get into that a little bit more later, but that's basically the fact that it causes kind of out of body and dissociative experiences.

    Perfect, thank you. And can you tell us a little bit about how ketamine made its way into the field of psychiatry from anesthesia?

    Yeah, so interestingly, I mean, over 20 years ago, they were actually doing research using ketamine, knowing that it had this sort of psychedelic out of body type experience to, they were trying to study schizophrenia actually and the positive symptoms of schizophrenia. So they were doing these studies and somewhere along there, they started to notice that there was some mood improvement. And so they actually did a real small study.

    The first one was published back in 2000. And I think back then, no one really thought much about this. It was very small.

    I think it was only like eight patients. And then again, in 2006, it was replicated. I imagine that one, as it was given IV and it's an anesthetic, right?

    And so I think obviously many in psychiatry thought this is kind of out there, right? I mean, it's not something that really took off at that time. My understanding too is because of the dissociation and it has a history of being used as a club drug as well, that created some barriers with regards to the FDA.

    So for a number of years, people were trying to develop a drug that worked kind of like ketamine but without the dissociative effects because of I think concerns with like the FDA and things like that, which of course never came to fruition.

    What about the terms R and S ketamine and maybe you could touch on the differences between those.

    Any racemic molecule, right, has R and S. IV ketamine that's typically used for infusions is what we call racemic ketamine. A year and a half ago, Janssen developed S ketamine in a nasal form, which they have a patent on, and that's just the S enantiomer.

    There was some thought that the S enantiomer is actually has a higher affinity for the NMD receptor than racemic, and it seems to be a slightly less dissociative molecule. So there are some differences there.

    You've mentioned dissociative properties a few times, and you also mentioned that this can be used recreationally. So could you discuss how medical use fits with this recreational use and also describe maybe the term K-hole?

    So with regards to recreational use, it tends to be a lot more than we use for mood. So mood doses are actually quite small. A typical starting dose, and what most of the literature is on, is actually on half a milligram per kilogram, which is about 20 times smaller than probably an anesthetic dose.

    And with recreational use, and that dose is over 40 minutes. In recreational use, it's, I think it's typically sordid. It's a much higher dose, it's usually done daily.

    Whereas with mood doses, we dose less frequently, usually two to three times a week, over two to three weeks for that initial ramp-up period. So it's a very different type of use. And then with regards to dissociative effects, there's kind of a range of dissociation that people can experience, starting with lower doses and just kind of a little bit of a floaty kind of feeling all the way to kind of out of body, seeing your body from the outside.

    And then even further to, like you mentioned, cave hole where the person doesn't really know they exist or they feel like a speck in the universe. And it's a lot more, it's this deeper, more psychedelic experience that's much, much deeper. And that's not really the goal that we have for mood doses.

    It can happen, but it's not very difficult. And certainly not the goal of treatment. So patients find that actually incredibly scary, right?

    So really the experience that we're aiming for is something much more comfortable than that.

    Okay, so just to summarize for our listeners, ketamine is a molecule that's been used in medicine for some time within the field of anesthesia. And it's also used recreationally, but in much higher doses than what we'd be using for treating mood disorders. And there were some very promising studies that were conducted, kind of examining its use within psychiatry in the early 2000s.

    Although it was quite kind of radical and different at the time, not something that people were really used to. And now it's really becoming more mainstream within psychiatry. And I was wondering if you could tell us more about where exactly it comes into play in the treatment of resistant depression, like the patients you see in your clinic, and like what kinds of patients would be suitable to receive this therapy?

    So one thing I think that's important to talk about when we say where does ketamine fit within the treatment resistant realm, I think is to talk about how important remission is with depression and how infrequently we usually are able to accomplish that. So for example, after about two antidepressants that a patient has failed, the chances of going into full remission with the third antidepressant is only 14% and it drops further and further with each medication trial. Many of the patients that come in have actually tried something like six antidepressants.

    And even if they respond a little bit, they haven't gotten it into remission. So I think that's an important thing to think about, that it's not just patients who are still extremely depressed and maybe meaning hospitalization or they have suicidality, that wouldn't have to get Ketamine. A lot of times it's a lot of patients who have tried a lot of treatments, but they haven't been able to achieve remission, even though they're not necessarily bedridden.

    So that, I mean, I mention it because it's a common thing that people ask. A lot of people think that, you know, my whole practice must be people who are like completely non-functioning. And that's not true.

    I think there are a lot of people who just partially respond to antidepressants. So that's, that's a big part of that. What was the other part of your question?

    I think you were just asking like where it fits.

    So yeah, thank you for that clarification around. Yeah, it doesn't necessarily need to be the most severe cases, but people who have it.

    And I think where this fits is different for different people based on their knowledge, right? But one thing that's important to know is sometimes people are looking at TMS, Ketamine and ECT sort of like as these treatment resistant modalities. And ECT has a potential for a longer term side effects.

    Ketamine with just a couple infusions really doesn't have any long term side effects or side effects in between infusions. So it can be a much safer option to try up front instead of jumping to ECT.

    And there's a lot of discussion about its use in kind of acute suicidality. Could you speak to that at all?

    Absolutely. So two things there. One, just from my clinical experience, I really think I've seen it save many people's lives.

    I've had patients that I was about to send to the hospital, we decided to try an infusion instead, and they all say the same thing after the infusion. They say, I can't make my brain go bare. And it just goes away.

    That doesn't mean it doesn't come back. But at least in that moment, they're in a safer place. Laurie Calabrese is a psychiatrist who also does a lot of IP ketamine.

    And she took some of her patients from her actual clinic and looked at them with regards to suicidality. And she found that patients that had suicidality with their depression were actually more likely to respond to ketamine and their suicidal thoughts resolved as well. Janssen, which we mentioned with S-ketamine, they have a second FDA indication that just came out that is not for suicidality per se, but basically for depression that has an imminent risk of suicidal thoughts.

    So this is coming more to the forefront. I think it's probably one of the most important things for people to take away, even if you never actually give ketamine, just knowing that it could potentially be very life-saving for a patient, I think is really important, even if they are not treatment resistant. The second indication doesn't talk about treatment resistance.

    It's if you are that severely depressed and suicidal, you should go to this right away, is basically what that indication is saying. And I have to agree that you don't need to fail everything before using it, especially if suicidality is something you look for.

    Are there any contraindications for ketamine?

    Sorry, are there other indications for ketamine?

    Are there any contraindications for ketamine?

    Contraindications for ketamine, yes. The most notable is probably going to be somebody who is actively psychotic or they have a psychotic disorder. And then we do use it, something bipolar disorder, but when patients are in a bipolar depressed state, so you want to make sure they're not in a manic state.

    That's a little bit trickier to do, but those would be the most common like contraindications really.

    Is there any risk of a manic switch with ketamine?

    There is in theory a manic switch, and I have seen it, actually with S-ketamine. It was a patient that was not diagnosed as bipolar, and so she was not on a mood stabilizer, and she got a little hypomanic, and we were able to kind of reverse things. So there is always that potential, which is why many people who do treat patients who have bipolar depression will have something like an anti-psychotic on board to kind of prevent any emerging medium.

    And I'm wondering if you could tell us about the efficacy or overall usefulness of ketamine as a therapy, maybe in comparison to some of the other therapies that we have for depression.

    So one thing that's important to talk about also is that ketamine is not easily translated across different sets, meaning that different people dose things differently, right? That there's no set way of doing treatment, which is why it's so important that we get more data on what actually works and what's the optimal way of using it. So depending on what you're looking at, some people will use half a milligram per kilo and they usually report a response rate as someone in the high 60s to low 70s.

    And a lot of people who do more dose titration to the patient and adjust their doses accordingly, and also maybe take off medications that might interfere like Lamictal, they will often say their response rate is closer to 80%. So somewhere between 70 and 80% is probably fair to say.

    And in terms of timeframes, how quickly does ketamine tend to work in alleviating those depressive symptoms and how long do the effects last?

    So it definitely depends on the patient. Some patients will have this sort of immediate antisocial effect or even an immediate mood lifting effect. And if you look at some of those like really early studies, that's what they were looking at.

    It's a single infusion and people did report some improvement in their symptoms. I would say that's not necessarily always the case. A lot of people take a couple treatments usually to start feeling better.

    We usually tell people somewhere around the third or fourth treatment, we start to see some functional improvement and that can look like just finding it a little easier. We do things, a lot of times it's the family that's starting to notice that or they shall come in and say, I cleaned my house this weekend or something that they've been trying to do for a long time that they haven't been able to. So that's kind of where we start to see efficacy.

    A typical series upfront is six infusions over like I said, two to three weeks. After that period of time, most people will need a booster infusion sometime around a month or so after that series. Now, at that month mark, it's usually just starting to fall off.

    We usually tell people somewhere around the third or fourth treatment, we start to see some functional improvement and that can look like just finding it a little easier. We do things, a lot of times it's the family that's starting to notice that or they shall come in and say, I cleaned my house this weekend or something that they've been trying to do for a long time that they haven't been able to. So that's kind of where we start to see efficacy.

    A typical series upfront is six infusions over like I said, two to three weeks. After that period of time, most people will need a booster infusion sometime around a month or so after that series. Now, at that month mark, it's usually just starting to fall off.

    It's not that they've completely relapsed. A lot of people would probably take many months to completely relapse, but obviously if you've responded, well, we don't want that. So in order to just kind of keep things going smoothly, somewhere around that month mark is pretty typical.

    It does require ongoing treatment. For the most part, it's a treatment and not a cure. It doesn't completely get rid of depression.

    Know that once people have had about three episodes of depression or they've been depressed for a long period of time, which it does tend to be this patient population, a lot of them will tell you they've had depression for 10, 20 years. Sometimes they find that they do best continuing treatment. What that regimen is is different for different patients.

    Again, some people only need one once every three months. Some people still need one once every six weeks. It's just different depending on the patient.

    And some young patients that have had a single episode of depression, I have been able to treat them and then we don't need ketamine anymore. So, but again, I think that's a different profile patient because they don't have that long-term history of kind of staying depressed.

    How many sessions would you do before you kind of come to the decision that maybe the patient isn't going to respond to ketamine?

    Yeah, with IV, I mean, I have seen patients get to that fifth infusion and I'm like, man, I don't think you're going to respond. They come in for that sixth one and they're like, I'm better. And so I've seen it.

    And sometimes people just start to respond at that fifth or sixth infusion. And then you might even keep going a little bit more with that kind of twice a week or once a week, keeping them kind of close together. So I think as long as you see some improvement by like five or six, it probably still makes sense to continue.

    Earlier, you mentioned that TMS and ketamine were two of the major TRD treatments, but you're pretty innovative in that you sometimes do both at the same time for your patients. So could you talk a little bit about that?

    This is something I kind of tripped on. I had a patient who responded really, really well to ketamine and then some stressors came up and you're not very anxious. And all of a sudden this ketamine wasn't responding to ketamine.

    He wasn't sleeping very well because of the anxiety and he wasn't responding to ketamine. We even tried repeating a little series of ketamine, increasing doses, increasing light, doing all of these sorts of things. It wasn't improving.

    So we decided to try TMS because of how he was doing. And a couple weeks in the TMS, we decided to re-challenge him with ketamine and he responded beautifully. I started looking into the literature and there actually is a doctor, Steve Best, who's done about 250 and he's published them.

    He does ketamine simultaneously with the TMS and sees some very nice results. I've also been able to treat some patients who maybe they've gone elsewhere and they have had some ketamine treatments and they didn't really respond very well. And we do TMS and we challenge them and they respond very well.

    So I did a presentation on this a couple of weeks ago. There's definitely a very clear synergy between the two mechanisms. And it seems like ketamine sort of potentiates the effect of the TMS.

    And that has been a great go-to for some of the patients. And it's also helpful if a patient doesn't seem to be, like they get better but they're not able to go maybe a full month between treatments because it can be very expensive, right? Ketamine is not covered by insurance.

    And so anything we can do to sort of lengthen that time between treatments can be very helpful. TMS is covered by insurance. So sometimes if we have a patient that's only staying well for maybe two weeks at a time, but they are better, something that makes sense in some of those patients is to do TMS and then re-challenge if they can and it seems to work better.

    So I think we've talked about the need for ongoing treatment. Are there other kind of limitations of ketamine treatment that are important to know about?

    Yeah, so I just touched on one, which is cost, not covered by insurance. Two, I would say limited availability, right? There's probably lots of areas of the country where there's just not really access to treatment.

    It's not an FDA approved treatment, so we don't have those trials that you usually would have that lead to an FDA approval, meaning we don't have long-term safety data. I've already alluded to the fact that we don't really have a clear sort of regimen in which to give the treatment with regards to doses and how you might escalate it. So there's not really consistency amongst treatment and then there's no clear right protocol either.

    So I think some of those things are certain limitations.

    Yeah, you just mentioned kind of the lack of information around different protocols across clinics. And part of the reason is there are no clinical trials, but in some other areas of medicine like oncology, that issue has been alleviated using real-world data or real-world evidence. So how do you see the field being able to utilize that for research purposes and maybe it'd be appropriate to talk about what ASKP is trying to do in the area?

    Yeah, so absolutely. So you're right, we'll probably never get this data with regards to like an FDA kind of, those trials are very expensive to conduct, but we have so many people doing these treatments. And I think if we were able to pull their data, it would be very useful.

    So there are some software platforms out there that allow us to have kind of real-time patient monitoring between treatments and then have the time treatment so that we can really kind of see and extrapolate and look at that data. Like you mentioned, I'm the president of ASKP and we're a national organization for providers, not just physicians, but also psychotherapists and other providers who are using ketamine. And so it's a large group that it would be great to have that data and to look at that data as well, to try to come to some of these conclusions and establish long-term safety data.

    So we have the information out there to get these things that we need. It's just not being done. And so this is something, you know, ASKP and several others have had some interest in doing.

    Yeah, I think it's definitely interesting. And so here in Canada, although things are slightly different, we also, we have our kind of our can-met guidelines that we follow. And ketamine in there is still considered an experimental treatment.

    So it will be, yeah, interesting to see how things progress in terms of-

    Yeah, even here, when a person comes in for a treatment, part of their consent form is that it says on there that it's not FDA approved. And, you know, that it's a treatment, not a cure, and those sorts of things as well.

    So thank you for talking about kind of Ketamine as a treatment and it allows us to put it in perspective with some of our other treatments like antidepressants and the neurostimulation. Taking a step back, are there any proposed mechanisms of action for how Ketamine can lead to resolution of symptoms?

    Yeah, so what we know is that in NMDA receptor antidepressants that it's most basic. Downstream from that, it seems to then turn on a number of pathways. It activates AmpOID, it increases BDNF, turns on mTOR, and these cause downstream signaling that seems to increase the way neurons will actually function and communicate with each other.

    So we seem to know that there's some sort of almost like neurodegeneration of the signaling, especially in the frontal lobe with depression, and that ketamine seems to be able to repair some of that. We have some interesting electron microscopy from rat neurons, where they show within 15 minutes that new dendrites are starting to bud right after ketamine. So there seems to be this very quick uptake of things like EDNF that help to repair some of that neuronal signal.

    I'm sure it's much more complicated enough, but you just don't know everything that it's doing downstream.

    You've been talking about IV administration of ketamine, but it seems that there are also new different types of administration, including intranasal as well as oral. Would you be able to speak to some of those and whether there's any differences in the effects and safety profile?

    Yeah. So there's a lot of difference between these. The most common ones that are used would be oral, and then we have intranasal, intramuscular, and intravenous.

    The first thing to look at is just how much is bioavailable. So with IV, about 100 percent is bioavailable. With IM, 90 to 95 percent.

    With IM, IM is 90 to 95 percent. Intranasal is, and it can vary a lot because it depends on how someone administers it, how much goes down the back of their throat. So somewhere between 30 and 50 percent is probably feasible.

    And then with oral, probably even less than that. So sub 20, so something like 10, 20, very small amounts. Because of all these different amounts of absorption, what you can kind of get out of them, how frequently you might have to administer changes.

    So for example, oral, because of the small dose that someone's getting, they would need much more frequent doses in order to probably see any kind of response. If at all. The other thing that's worth noting, and we haven't talked a whole lot about is just the experience of the treatment itself.

    And that varies a lot with the different modalities, not just because the dose is different, but also because of how it's given. So for example, with IV, you'll usually do anywhere from about 40 to 60 minutes. It's a pretty typical infusion.

    And like I use a syringe pump. So you're literally telling the pump like how many micrograms to give like right every bit. And so you can really control keeping that person in that sort of dissociated state for that period of time.

    IM tends to get a lot harder, a lot faster, and then kind of wear off. And then intranasal tends to also be wear. It's not as like long, it'll kind of go up and then sort of come down rather than sort of stay even.

    And oral can have kind of a variable sort of experience, but usually a very short period of time. So there's some thought that maybe, and again, we're not sure how to exactly predict efficacy, how to predict dose, but there's some thought that maybe the time spent dissociated, or the nature of dissociation, might have some sort of correlation to response. There's some data out there for that, it's not a whole lot of data out there for that, but that's where you start to see a big difference with those also.

    Yeah, thank you for that. I think it's also very helpful to get a sense of what it's like from the patient perspective when we are talking about different treatments like this. In addition to the different administrative routes, there's sometimes discussion around a purely medical model of getting the ketamine, and then ketamine-assisted psychotherapy.

    I mean psychedelic-assisted psychotherapy is a growing area of interest, and although ketamine is not a classical psychedelic, it can be used in this way, is my understanding. Do you have any thoughts about that?

    This is a great question because there's the possibility of getting both in a treatment, where you're getting that medical model because at the end of the day, it's still a medication, it's a molecule that's hitting that receptor and causing these downstream things that we talked about, and that's that medical piece of the treatment. The other side of it is especially in not necessarily the higher doses with deeper dissociations, but more that in between area, patients can often engage in therapy when they're in those states. That's incredibly useful.

    This is very useful in patients who have PTSD. What it allows them to do a lot of times is to experience emotions or to see things from a perspective that maybe they hadn't seen before. Doing therapy in that space can be incredibly useful to be able to explore emotions that they might not have otherwise.

    I think there will be more and more of this as time goes on. MDMA is on its way to being FDA approved for PTSD, but in conjunction with therapy. This therapy piece I think is going to become more and more important as well.

    Is there any data thus far comparing IV ketamine without therapy with ketamine-assisted psychotherapy?

    I don't think there's really a direct comparison. I think it would be a little tricky because it would be, I guess, one population. You probably have to take out the trauma from that population and then look at it.

    Then the question is, does the dose matter more than the therapy?

    Has anyone tried to do maybe a hybrid model where you are doing the medical model of IV, but as you mentioned earlier, maybe there is a month in between. Would sending that person to psychotherapy improve things in your mind?

    Oh, sending them in addition to the IV. Not at the same time. I would say 98% of my patients are in therapy.

    I highly, highly, highly recommend therapy. Even if it's not during, it can be after, there's some data that showed that 24 hours after infusions, particularly, we don't hold to have therapy during that time. There's a lot of reasons why therapy can be useful.

    Besides just working through things from the past, one of the main things is it's a rapid and acting antidepressant. Sometimes you will have patients that were depressed their entire life, go from not functioning, go from that to really remission in a number of weeks. That in itself is jarring.

    While it's exciting, it's something the patient may not have ever thought they would be able to achieve. Now, it's how do I piece my life back together? While I was depressed, I lost friends, I didn't have a job, I wasn't doing all of these things.

    But now that I feel good, I want to do things. Sometimes patients can get really overwhelmed by that. So this is where therapy can become really useful also.

    You alluded to this a little while ago, but just talking about maintenance and keeping people well in between sessions, do you tend to use concurrent antidepressant treatments or other forms of therapy?

    Again, that's totally anecdotal. But in my experience, I have noticed that patients who stay on antidepressant tend to stay, they don't need infusions as frequently. For esketamine, the FDA will actually says that it must be taken in conjunction with the oral limiters.

    So that's part of the label. So I do, I do a lot of that. So in addition to just doing ketamine or TMS or something for my patients, I often adjust medications to optimize things with these modalities.

    Thank you so much. I think we've definitely learned a lot about kind of how ketamine came to be used in psychiatry and the current state of things and different applications for it. Do you have any thoughts or ideas about the future of ketamine research and where expansion might happen next, different patient populations?

    I think ketamine became the medication that we used for this treatment with TRD because it was already had an update group, although it was in anesthesia, so it's accessible. Things like MDMA and psilocybin, they're not accessible, they're not legal. And so I think the reach on those have been more difficult to use, right?

    And that's why these trials going on now will ultimately lead to probably FDA approvals and we'll be able to use those treatments. Interestingly, I mentioned earlier, for a number of years, there's a lot of research going on on this NMDA receptor and how do we... I think ideally they do not want to use ketamine for this treatment.

    They were actually trying to just find something that would work with the receptor. And cause the antidepressant effect, maybe without dissociations, just to be a little cleaner. And they weren't able to achieve it.

    There were even other NMDA receptor antagonists medications that got to face three trials and they didn't have dissociation as part of it. And they didn't get a group. They could work.

    So that's certainly been, I think, probably a long journey. And I think things have shifted a little bit now to more some of the psychedelics that we do know, like I mentioned, and those are actively undergoing clinical trials. And I think there will be a lot of that in the future.

    Like I mentioned, it will probably involve a lot of therapy as well, which I think is great. But this is very much we're going to see a lot of this in the future.

    Given that psychiatrists are going to be the ones administering ketamine, and maybe a lot of psychiatrists are not exactly used to administering ketamine, is there certain safety risks that we have to watch out for during administration or shortly after?

    So a lot of psychiatrists actually don't get ketamine, right? I think that's another reason why there is this sort of access issue. And in ASKP, for example, we have a variety of different specialties.

    So there's actually a lot of ER doctors and anesthesiologists who are giving this treatment. And then some other physicians, both different specialties as well. Going back to your question, though, the doses that we do use for mood with ketamine in psychiatry are actually very, very safe.

    It's very low there. I think education is definitely important. And it's one of the reasons we also created ASKP is the collaboration piece is really important.

    I was actually trained by two anesthesiologists, went up to their practices and did treatments with them. They kind of really mentor me. And I think that was that was very important.

    I don't think as a psychiatrist on my own, I could have just gone out and just started doing this. I think you have to work within your comfort level and constant learning and collaboration is really important. As it becomes more and more popular, I think there are more and more opportunities to do so.

    And I think it's just very important. I know for myself, I could never have done this on my own. So when I'm giving an IV treatment, I have an EKG, I have a pulse ox, and I've got blood pressure.

    I'm watching pulses. Those are the things that I watch during an infusion. It's very common to see transient increase in blood pressure and then it tends to come right back down.

    A lot of some of the difficult things to manage during a ketamine infusion is actually some of the behavioral type of things. So it's actually some people will struggle with that losing control out of body type of reaction. And so that sometimes it's a matter of walking them through that and helping with the anxiety.

    And then nausea, I guess, would be the other one that you probably see, but very easy to manage.

    I'm curious to hear your thoughts on, I guess, this part of psychiatry as a whole. This is a podcast for medical trainees, and it seems like there is a push to get more interventional or more intensive, I guess, modalities within psychiatry. And we've talked about psychedelic medicines, things like that.

    So I guess in terms of medical training, how do you see this playing out over the next 10, 20 years?

    Yeah, I feel like psychiatry will have more and more of these sort of interventional-type treatments as these new modalities come out. It will be interesting to see how they actually incorporate those into training programs. They have a few interventional psychiatry fellowships.

    So this time Yale has one, for example. And they focus on TMS, PCT, and Ketamine. So IV, Ketamine, and ASKP.

    So there will be these opportunities for people who want to seek this out and learn more about it.

    Yeah, thank you. And for our listeners, we'll also include some resources in the show notes about places that you can learn more about this topic.

    I'm curious if you could speak a little bit to the data on PTSD or OCD or other indications. Today, we've mostly talked about depression and TB.

    So the data, the actual published data on PTSD as well as OCD with ketamine is much more limited. OCD as a whole is pretty difficult to treat. I have had some success with doing, I've had to do what seems like longer and higher dose infusions in OCD patients, but there seems to have been some improvement.

    I actually typically combine that. I have a Brainsway H7 helmet, which is for OCD specific with TMS. So we'll combine those two treatments a lot of times.

    And then for PTSD, again, not a lot of published literature for PTSD, but there is some. And it's certainly seems really useful. And again, this is sort of that out of body type of thing.

    “I think it's the same reason. I think MTMA will probably end up kind of replacing Ketamine from the PTSD realm. I mean, I'm not 100% sure, but I would imagine maybe that, you know, they're trying to make that very much protocol driven, very set training ahead of time, you know, that people have to go through.

    So it will probably have a bit more rigorous and a little bit more clear like how to do it.

    “But definitely, I mean, people definitely tend to use it in regular depression, bipolar depression, PTSD, OCD, you know, even some anxiety. And a lot of times patients who have anxiety, maybe there's some history of trauma there. And sometimes that anxiety especially will respond well to Ketamine.

    Thank you so much, Dr. Prashad, for your time and answering our questions today. I think we all learned a lot about Ketamine and its use within psychiatry. Sounds very promising and a lot of new ground to break in the future.

    Is there anything you wanted to leave our listeners with before we part ways today?”

    The only thing is I touched on this already during the talk, but I think it's really important as a takeaway that this can be a life-saving treatment for some and somebody struggling with suicidality is something to think of sooner rather than later. I think it's just important that, like I said, even if you never actually administer Ketamine, I think all psychiatrists need to know that piece about Ketamine. I think that part is really important because I don't think we have anything else in psychiatry that works like that for suicidality.

    That's really important.

    Great. Thank you so much.

    Thank you so much for joining us today and learning about ketamine. PsychEd is a resident-led initiative at the University of Toronto. We are affiliated with the Department of Psychiatry at the University of Toronto, as well as the Canadian Psychiatric Association.

    The views within this episode do not necessarily represent those of the U of T or the CPA. This episode was produced by myself, Dr. Nikhita Singhal, Jimmy Qian, and Gray Meckling. This episode was audio edited by myself, Chase Thompson.

    Our theme song is Working Solutions by Olive Music. And finally, a special thank you to our guest, Dr. Sandhya Prashad. If you want to contact us, our email is psychedpodcast at gmail.com and our website is psychedpodcast.org.

    Thanks so much for joining. See you next time.