Overview of Rapid-Acting Therapies in Major Depressive Disorder (MDD)

Welcome to this Patient Care Online presentation titled “A Conversation on the Role of Rapid Acting Therapies in the Management of Major Depressive Disorder.” I’m Roger McIntyre, professor of psychiatry and pharmacology at University of Toronto, Canada, [and] I’m board chair of the Depression and Bipolar Support Alliance in Chicago, Illinois. I’m joined today by a good friend and colleague, Carmen Kosicek, who is the CEO and the founder and PMHNP [psychiatric-mental health nurse practitioner] prescriber of the Alay Health Team, Psychiatry in Tucson, Arizona. Carmen, a big title there. In today’s discussion, we will focus on a topic we’ve been hearing more about in the field, that being the role of rapid-acting therapies, specifically GABAA receptor modulators, in the management of major depressive disorder. Our conversation will explore their mechanism of action, their clinical utility as an effective treatment, and the ongoing research efforts within this area. Let’s see if we can start off with what a rapid-acting antidepressant [is]. What does it even mean?

Carmen Kosicek, MSN, PMHNP-BC: I think that’s such a great idea. And what a wonderful question. Because when patients come to me and they’re depressed, the very first thing that they want to know is, “Can you help me? Then, “How long is it going to take?” So I think the first question is, what truly is the definition of fast-acting? Obviously, we want that to be like now and tomorrow. It never happens that way. So the biggest question that I would first pose is, what is normally in your toolbox as a prescriber that you’ve been reaching for, and what does that timeline look like? Sadly, for many, what I have seen when patients are referred to me or even other peers of mine, it is a traditional medication that maybe has been around for 30 years. And you know how this goes. We’ll start on a titration dose that’s not really efficacious and then we’ll go up to help limit GI [gastrointestinal] upset. Then, from there, [it’s] maybe 4 to 6 weeks before we increase the dose, and this goes on for about 3 to 4 months before they hop from med to med to med. I personally don’t call that fast-acting. So I think the definition first needs to be looked at of what truly is fast-acting. What I like to do with my patients is to look at the calendar and give them the outline of hope of time. So, for example, if it was the beginning of fall, September, for example, and a patient comes to me who has depression. I like to showcase that there are options available to them, not only of what I can use today, like what is on the shelf at the pharmacy today. But if that’s not the medication for them, what is coming, and what is in the pipeline? For present time, what I use of what’s available today, I can confidently tell them that within 3 to 4 weeks I can help to turn them around, which means at this time of year I can position them positively for the best holiday season that they’ve likely had in a long time.

Roger S. McIntyre, MD, FRCPC: That’s a great start and a very, pragmatic approach to it. I was sort of thinking to myself, Carmen, as I was reading the question, a bit of a historical bent, and that is when we think about the treatments of psychiatry, when we’re focusing on depression, today, conventional FDA-approved antidepressants on the average would take at least, as you alluded to, 2 to 4, maybe even longer, 2 to 6 weeks, to offer adequate symptom relief. In other words, what’s considered a benefit that’s clinically meaningful. We all know STAR*D [sequenced treatment alternatives to relieve depression study] and STAR*D it was reported that up to half, even more than half of people did not even begin to show much improvement beyond 6 weeks. So I think that no one needs to be convinced this is far too long for people with lived experience. And, frankly, all of us would like to see symptom resolution immediately who would not.

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