Ketamine for Suicidal Ideation: Meta-analysis

Ketamine for Suicidal Ideation: Meta-analysis


Hello! I’m Dr. Wegdan Rashad and you are listening
to the Psychopharmacology Institute podcast. We are an educational platform that is passionate
to help you, the mental health clinician, stay up-to-date and sharp on the latest in
psychopharm. Join me every two weeks where we learn about
interesting and clinically relevant topics that you can apply right away in your practice. Before we get started, why don’t you go
to piupdates.com to sign up on our website, earn CMEs, and receive regular psychopharm
nuggets of joy? PI stands for Psychopharmacology Institute,
by the way. So, go for it. [music break] Today’s episode is kinda different from
the regular podcasts. I am excited to share with you a snippet from
a new CME podcast that we have called ‘Quick Takes’ and basically what Quick Takes aims
to do is to keep you informed about psychiatry research. We have Dr. Jim Phelps taking us through the
latest and most clinically relevant psych research findings, he discusses it and we
reach practical conclusions from it. So if you’re keen to stay up-to-date on
the literature but don’t quite have the time to read publications, Quick Takes would
be perfect for you. I handpicked a ripe episode to share with
you about ketamine. We spoke about the basics of ketamine and
esketamine in the last episode, remember? Now, this snippet is about ketamine in the
context of suicidal ideation. Is it good enough? Is it that wonder drug we are all hoping for? Listen carefully! And I’ll see you very soon. [quick takes music intro] Dr. Phelps: Hi! Jim Phelps here for the Psychopharmacology
Institute with a Quick Take. Here we go! The first is a new meta-analysis of ketamine
as a potential means of addressing suicidal ideation, perhaps, for example, in the emergency
department to prevent having to hospitalize a patient. Is that a potentially viable strategy? Does ketamine have enough clinical effect
relative to a controlled procedure to rely upon in that kind of a setting, as an emergency
treatment of suicidal ideation? Let’s take a look. This is a meta-analysis from Samuel Wilkinson
and colleagues that was published in the *American Journal of Psychiatry* in 2018. This is kind of a replication of an earlier
meta-analysis that found that ketamine does have a specific antisuicide effect. Let’s look at that question again with these
new data. First of all, the sample size was pretty good. We had 167 out of the 298 patients who participated
in 10 ketamine trials. So, 167 of them had enough suicidal ideation
to come into this part of the trial, where we looked at their suicidal ideation scores
on measures of depression. Some of the studies used the MADRS, some the
HAM-D, some the QIDS-SR (the Self-Rated Quick Inventory of Depressive Symptoms), and some
the Beck Depression Inventory. Looking at just the suicidal ideation score
from those studies, what we see is that ketamine has a quite dramatic effect on suicidal ideation
on Day 1, a substantial reduction that on most of these measures persists over the following
7 days. So, again, that makes this plausible as an
intervention that one could use in the emergency department or in the early stages of a hospitalization
for suicidal ideation. The results are quite robust, but it depends
on whether the control condition was a saline injection because this was all intravenous
ketamine. So, is the control condition a saline injection? In some of the studies, it was a midazolam
injection or a rapid-acting benzodiazepine replicating some of the immediate effects
of ketamine. What was seen is the effect size is much stronger
if it’s a saline injection. And that comes as no surprise because you’d
have people who got a saline injection experiencing nothing and probably intuiting that they were
in the arm of the study where they got the placebo versus the midazolam, where they experienced
something and could wonder. And clearly, that had an impact on their suicidal
ideation scores in that the effect size was 0.9 in the early days of the study, in that
very first day if it was a saline injection. On the other hand, if you only looked at the
midazolam studies, the effect size was 0.6. What we learned is that you have to be careful
in these studies. An active comparator like midazolam is a more
realistic control condition than saline. Nevertheless, 0.6 is clearly up there. Remember, as an effect size, 0.5 is likely
to be clinically significant. Interestingly, that separation from placebo
is maintained still, with an effect size of 0.4 at Day 7. So, it’s realistic that you could think
that you might administer ketamine urgently and not have the suicidal ideation just recur
on the very next day. There is time, or you are buying time, for
other interventions to be put in place. So, it is an exciting potential tool. Certainly, in our group in Oregon, this is
being actively considered in trying to mount a system whereby we could offer this in the
emergency department. I will note that in this study, the authors
are sort of a “who’s who” of people having done ketamine research. If you think that having to receive money
from a pharmaceutical company or being in a position to profit if ketamine is demonstrated
to be an effective intervention, if you think that that might affect research like this,
then you’d want to know that many of these authors do have financial connections to pharmaceutical
companies. And several are holders of patents that will
profit if ketamine goes into active use, at least in some fashion. So, there is a bit of a potential conflict
of interest here in terms of the researchers, although the lead author has no such conflicts. And several of these people are working for
the National Institute of Mental Health in the United States, where, hopefully, even
if they have some connection to the pharmaceutical industry, it’s not likely to be a main driver
of their clinical work or their clinical research. [music break] In summary, we could say that this new meta-analysis
of 10 randomized trials supports the idea that ketamine can specifically address suicidal
ideation—sometimes even without similar reductions in depression. And the effects persist long enough, 7 days,
for this to be used in the context of an emergency department intervention in which you’re trying
to avoid hospitalization for someone presenting with suicidal ideation. Lots of other issues need to be worked out
in terms of long-term safety, potential complications, and people potentially wanting to use this
in some fashion to go through the “ketamine experience”. But targeting the symptoms specifically, it
does seem to work. Really interesting stuff! I hope you learned something new today. Before I sign out I would encourage you to
go to PIupdates.com to earn CMEs, there you can become a premium plus member. After you become a premium plus member you
will have unlimited access to all our content and earn CME for the Quick Take you just listened
to. If you are a psychiatrist in the US or Canada,
we offer a bunch of CME and SA credits. The following people participated in this
episode: Dr. Flavio Guzman as the general editor, Andy Rhode as the audio engineer,
Pamela Gonzalez as the project manager and myself, Dr. Wegdan Rashad as the host. And a special thank you to Dr. Jim Phelps
for the Quick Takes episode today. Thank you for joining us in today’s podcast
until the next episode, goodbye!

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