Emerging Rapid-Acting Intervention Options for the Treatment of MDD

Following his insightful session, “Rapid-Acting Innovations in the Pharmacological Management of Major Depressive Disorder,” at Psych Congress 2024, Snoben Kuruvila, MPAS, PA-C, sat down with Psych Congress Network to discuss emerging developments in major depressive disorder (MDD) treatment. In this video, Kuruvila covers promising rapid-acting antidepressants, the benefits of these novel interventions, and the importance of shared decision-making between patients and providers in navigating treatment options.

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Snoben Kuruvila, MPAS, PA-C: Hi, my name is Snoben Kuruvila, and I’m a physician assistant at the Center for Depression Research and Clinical Care at UT Southwestern.

Psych Congress Network: What are the most promising rapid-acting antidepressants currently available or in development for the treatment of major depressive disorder (MDD)? 

Kuruvila: Per our session today, we discussed multiple novel treatments including IV ketamine, which has been off-label usage, as well as nasal ketamine, which has been utilized for MDD with suicidal ideation and treatment-resistant depression (TRD). We have also discussed dextromethorphan and bupropion combination, and these medications, along with non-pharmacologic options such as the Stanford neuromodulation therapy, are options that are now available for the treatment of MDD.

PCN: How do rapid-acting antidepressants and psychedelics differ in their mechanisms of action compared to traditional antidepressants? 

Kuruvila: That's a very challenging question in regards to the mechanism of action, as there's no real consensus of how [the disease is] being treated. We do know that [rapid-acting antidepressants] are working on different receptors—not the serotonergic receptors, but more so the glutaminergic receptors. The idea is that with the glutamate receptors, we are utilizing N-methyl-D-aspartate (NMDA), as well as other parts of the brain, in order to find the brain circuitry of people with depression—in these people who have dysfunctional circuitry, we can try to see if there's a benefit with these new, novel medications.

PCN: What are the potential benefits of using rapid-acting medications in managing acute depressive episodes versus chronic MDD? 

Kuruvila: It’s really important because when we talk about rapid acting, it's one of those scenarios where someone in an acute MDD episode would like to have something that works really fast. In our old standard of care, we would still prescribe the same medications and they would not see any immediate results. What we have to do is educate the patients in helping them [to understand] these rapid acting and innovative medications, but also saying that MDD is a chronic disease. Thus, once we treat them with something that is initial for their acute treatment, we also need to make sure that they're compliant with their long-term care as well.

PCN: How are these rapid-acting interventions changing the standard of care for depression, particularly in cases of treatment-resistant or severe MDD? 

Kuruvila: There’s a definite shift moving towards interventional treatment, and this is allowing us a wider array of options in treating our patients. It's useful, but we also need to educate providers in how we utilize these novel treatments in order to treat our patients the best.

PCN: What role do patient preferences and shared decision-making play when considering the use of these newer, rapid-acting treatments for depression? 

Kuruvila: Shared decision-making plays a crucial and very pivotal role in making these decisions as far as utilizing rapid-acting treatments. I believe discussing these [novel treatment options] with the patient is going to be key in allowing them to make an informed decision with the provider, so that the provider and patient can work collaboratively together.

My name is Snoben Kuruvila. I hope that this talk was helpful and that you can utilize this in your clinical practice.

Snoben Kuruvila, MPAS, PA-C, is a board-certified physician assistant in the Department of Psychiatry at UT Southwestern (UTSW) Medical Center at Dallas, TX, with extensive experience in treating patients with substance use disorders and in addiction medicine. He is also a clinical investigator at the Center for Depression Research and Clinical Care at UTSW and is currently a part of several studies focusing on interventional treatments for depression and substance use disorders.