Defining Features of Rapid-Acting Therapies in 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.