Dan Iosifescu, MD: Current and Future Ketamine Use


Esketamine nasal spray is currently relegated to a specific depression patient population, but that may not be for long.

Esketamine nasal spray’s indication as a physician-managed, short-term therapy for treatment-resistant depression is a boon for psychiatrists treating a very at-need patient population. But it’s also a short start to a therapy that has bigger potential.

In an interview with MD Magazine®, prominent ketamine researcher and Associate Professor of Psychiatry at NYU School of Medicine, Dan Iosiefescu, MD, explained the benefit of esketamine’s first approval, and where else the much-discussed drug can benefit psychiatry.

Iosifescu: For me as a psychiatrist, the fact that you can have a very quick resolution of severe depressive symptoms, and also other studies including ours show that even people who don't have depression but have severe suicidal ideation can get better quickly—that's huge.

And primarily, I see this as a way to buy ourselves time for other things that are effective in the long run. To be able to implement it the person that is not acutely ill and not so depressed, they may be able to engage in some treatments that require the subject to participate—for example, psychotherapy. When you are horribly depressed, you can't even meaningfully engage in it.

So it's important to have this kind of short-term boost.

Do you imagine ketamine has clinical use in other psychiatric conditions?

So, there's 2 parts to your question. One is, does ketamine have application—or esketamine have application for other disorders, and the answer is yes. And there are studies, including from our group, that ketamine does work for PTSD, and also there are some data from a group at Columbia for obsessive-compulsive disorder, and there's a few other conditions where there's good signals—bipolar depression, for example. But the data is more sparse in those indications than in treatment-resistant depression.

Now, you mention micro-dosing, and that typically involves not necessarily ketamine, although we have recently published a study where lower doses of ketamine also tend to have an effect—although smaller effect. But micro-dosing is usually a term used in conjunction with psychedelics such as ecstasy and other types psilocybin, and other types of psychedelics. And there are some very interesting preliminary studies coming out, including some from our colleagues here at NYU suggesting that there might be an effect.

This is very, very, very difficult research to do, the main reason being it's nearly impossible to have a masking of the psychedelic effects. So, the traditional way to test a treatment in medicine is to do the randomized, placebo-controlled study. It's really, absolutely impossible that someone who would get the actual psychedelic at 1 time and the placebo in another time will not know the difference.

With micro-dosing, it may be a little bit easier, but even then, people would pretty much figure it out. So there's that, and the scarcity of funding makes the research go a little bit slow. But there's signals that this could be also very interesting. But it's a little bit early to tell whether the enthusiasm that a lot of people have about it will actually pan out, because if you look at what actually happens in one of these sessions, it's a very intense change that is pretty much a very intensive psychotherapy session, plus the psychedelic.

So whether you're seeing an effect of that intensive psychotherapy or the pharmacological effect of the psychedelic remains to be seen.

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