Dosing Considerations of Zuranolone in MDD

EP: 1.Overview of Rapid-Acting Therapies in Major Depressive Disorder (MDD)

EP: 2.Defining Features of Rapid-Acting Therapies in MDD

EP: 3.Communicating With Patients About MDD Treatment

EP: 4.New Treatment Options in MDD

EP: 5.GABAa Receptor Modulators for Treatment of MDD

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EP: 6.Dosing Considerations of Zuranolone in MDD

EP: 7.GABAergic Modulating Treatment Considerations in MDD

EP: 8.Potential Adverse Effects of Zuranolone in MDD

EP: 9.Practical Considerations of Zuranolone Use in Treatment of MDD

EP: 10.Closing Thoughts on the Treatment of MDD

Roger S. McIntyre, MD, FRCPC: And you know, what's interesting is that when we talk about the rapid or the fast-acting effects of, in this case, GABAergic agents in adults with a type of depression, we're talking postpartum depression, which is [a] type of depression. The immediate question that jumps out because, look, many colleagues joining us are very experienced. They know how pernicious, how chronic, how malignant depression can be, how relapse-prone it can be. And, so, when we think out loud to ourselves, “Hang on. If I'm prescribing an antipsychotic to a person with schizophrenia or I'm prescribing anxiolytic to someone with GAD or generalized anxiety, or I am prescribing an SSRI [selective serotonin reuptake inhibitors] to a person with depression, we've been telling them to take the medications every day and now we're saying something slightly different.” In other words, what we're saying is it's really a 2-part story and that is, we're saying we have treatments that are rapidly alleviating depressive symptoms in a way that's meaningful. And to finish the sentence, you don't need to keep taking it, that the prescription for zuranolone, for example, is about 2 weeks, we’ll say. But that doesn't mean the patient keeps taking it day in, day out, day in, day out. How do you think that's going to be received by patients?

Carmen Kosicek, MSN, PMHNP-BC: I think it really is how it's keyed up by the provider. And think about it, this has historically already been set in precedents in the medical community with, my biggest example that jumps to mind, is antibiotics. If we would take that pink pill that sometimes people like and some don't like for almost a whole month, and then they changed to where you could just take a pill for a couple of days or, even, I think when it first started, a week. So, it's really the same thing. And I think what the education needs to be focused around is exactly the same thing. You know, when you think about it, depression for many, not all, has a cycle or a pattern to it. For some it is chronic, long, even every day. But the definition then is something that I really tease out with my patients. Is it that your depression is not making you function at all, like you're in bed all day? Or is this a long-term depression where you can get up and go to work? But that's about all that you can do. There's a pattern. There's a cycle that I can sometimes unearth, and it's no different there then let's go for the win where we can. There's not a one-size- fits-all, but for the opportunity that arises. I really think it will be in volume for the majority of our patients to dose for 2 weeks. Just like in the antibiotic world, some people do need a redose and the same thing will happen or again a couple of months down the road you could get sick again and you need a redose with the antibiotics. I think it's really a great analogy to give to showcase that here in mental health, no different than in physical health, could be that we can wipe it out with a 2-week treatment of an oral pill and if not, there's hope, we can come back again, circle around and really do short-term treatment. You know, I also think that this is really important to discuss because now with different age ranges of people and different cultures in the US, not everybody is open to taking medications every day for mental health.

Roger S. McIntyre, MD, FRCPC: Yes.

Carmen Kosicek, MSN, PMHNP-BC: Finally, we have opportunities to showcase. It doesn't have to be that way. What I see a lot in the younger generations, especially, again, with cultural sensitivity, is if their families realized that they were seeking treatment, it's almost kind of shunned or looked down upon because of the older generation’s thought process on mental health. The younger generation is very open to it and they are absolutely begging and waiting for providers to offer them short-term, fast-acting solutions to where it's not a medication every day. They're trying to have that fine line dance of, you know, immersing in the American culture as well as being cognizant of the culture from which they grew up in, even if it’s in the United States. But that long-term familial culture that has been ingrained about mental health. So, I think it's really important for all providers not to just take a class on cultural diversity, but to really see what is in front of you. What about age diversity? What is the perception for people of polypharmacy vs deprescribing? All of this comes into play, especially when you're talking about MDD [major depressive disorder].

Roger S. McIntyre, MD, FRCPC: All very good points, Carmen. I agree with all of that. And you know, I'm thinking as well, when I first heard about targeting GABA and thinking to myself, well, how is that different than a benzo[diazepine]? Well, as we talked about earlier, location, location, location, and there's different functional consequences with different GABA receptors and zuranolone is targeting a different type and different location of GABA receptors. And then I thought to myself, “Well, hang on, if the treatment is only given for 2 weeks, is that going to be sufficient at the biologic level?” And I would say, again, we start off with a bit of humility. We are not clear what the mechanism of action is or mechanisms are of antidepressants, but there is in fact a hypothesis that the effect of GABAergic modulation with a treatment like zuranolone ignites a molecular cascade. In other words, there's a series of molecular events that happen that set in motion an effect that's thought to be therapeutic, and therefore you don't need to keep taking the treatment beyond 2 weeks. Now, as you said, life is not perfect. Some people will need periodic boosters and that's not new. We see this with cognitive behavioral therapy as well. So, we'll have to come back for a bit of a booster therapy, things of that nature.

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