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Defining Features of Rapid-Acting Therapies in MDD


Roger S. McIntyre, MD, FRCPC, discusses the history of psychiatry and the conventional treatment and response times, leading into the current treatment armamentarium for treatment of major depressive disorder (MDD).

Roger S. McIntyre, MD, FRCPC: When you look back at the history of psychiatry, psychiatry has looked at this. For example, way back in the archives of the history of psychiatry, sleep deprivation was a very common treatment for people who were on the inpatient unit, who had terrible, severe, persistent depression. And lo and behold, 1 or 2 nights [later,] they were out of their depression. Bad news was at some point you [have] to go back to sleep, and you go back to sleep. The depression came back, so it didn’t seem to be too practical, but was certainly very conceptually interesting. As I think out loud, I think there’s other modalities that offer some type of symptom relief that can be quite meaningful fairly soon after administration. I think electroconvulsive therapy, for example, on the inpatient unit usually benefits most patients within 1 to 2 weeks, although we know there’s lots of variability and differences between patients. If I move over to the medication area, we have examples in medicine, in psychiatry, where some of our medications work pretty [quickly]. I think about a benzodiazepine to treat anxiety or an opioid to treat pain or even a stimulant to treat narrowly defined ADHD (attention deficit/hyperactivity disorder). But we’re talking about major depression, and we’re back to this definition again. Clearly, 4 to 8 weeks can’t be considered rapid-acting or fast-acting. And there is, in fact, a working definition…that many people have been considering, [that it] is a treatment that offers benefit within 1 to 2 weeks; a benefit that’s clinically meaningful. And the FDA has precedent for this in the sense that we already have FDA-approved treatments that are rapid-acting. For example, there’s a dextromethorphan-bupropion combination that’s approved as rapid-acting. For me, it’s a bit like, how long is a piece of string? Well, it depends on how you define the piece, the length. It depends on how you arrive at your definition. But I think in the field where the clinical community, the academic community, certainly the regulatory community, [they seem] to be saying it isn’t 4 to 6 weeks, it’s something earlier than that. And I think we could probably split hairs a bit where that line actually is. But certainly we’re seeing precedent for separation early, for example, within a week as being that that time some would say 2 weeks. But I’m going to sort of go a little more conservative on that 1 week. And I don’t think anybody needs to be convinced or explain to why this is so relevant.

Transcript is AI-generated and edited for clarity and readability.

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