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Clinical Pearls

Unmet Needs and Limitations in TRD and MDD Treatment

Explore the current challenges in treating major depressive disorder (MDD) in a discussion with Brooke Kempf, MSN, PMHNP-BC, hospitalist at the Hamilton Center, and Rakesh Jain, MD, MPH, clinical professor, Texas Tech - Permian Basin. Jain and Kempf delve into the unmet needs of patients struggling with partial response and treatment-resistant depression (TRD), highlight the limitations of traditional monoaminergic therapies, and share their hopes for future advancements in depression treatment. 

For more insights on major depressive disorder, visit the MDD Learning Library.


Read the Transcript:

NP Institute Online Learning Hub: Can you share the key unmet needs associated with MDD, particularly regarding partial response and treatment-resistant depression? 

Brooke Kempf, PMHNP-BC: Rakesh, when it comes to treating major depressive disorder, our current treatments have kind of left us with a lot of unmet needs. So, some of the things that I think about when I think of the ways that we've been treating depression for a long time, I just think about true lack of efficacy. We're sometimes getting patients better, but not necessarily getting them 'well.' I feel like there's a lot more that we could be done. What do you feel like some of the unmet needs are?

Rakesh Jain, MD: Yeah, it's the best of times. It's the worst of times for our patients. We have more and more treatments, but so many patients are left partially treated. And the truth of the matter is some people just don't get what they're looking for. And Brooke, it's not just depression that bothers me. It's the suffering that they endure as human beings and as family members. And here's the other dangerous thing, Brooke, which is the longer a depression has gone on, the harder it is to eradicate. You've seen that in clinical practice? Yes.

Kempf: Oh, absolutely. Yeah.

Jain: So the unmet need we have is our treatments aren't all that effective. The side effect burden can be quite substantial and I think we are too monogamous with monoamines. We have to break up that relationship.

Kempf: Yeah. We're doing a lot of the same.

Jain: We're doing a lot. That's a nice way to put it. We're doing a lot of the same and getting frustrated in the process. So it's time to reconceptualize depression, maybe not reject what we already knew. But to bring in new thinking.

Kempf: Yeah, I like that.

NP Institute Online Learning HubWhat are the current limitations of traditional monoaminergic therapies in treating TRD?

Kempf: Rakesh, when it comes to our current treatment options, we know we've been treating antide- or sorry, major depressive disorder, the same for a long time with antidepressants that work on monoamines. When you think of that approach, some things come to mind for me in how we could do better. I think the number one thing that I think about is the time it takes for these to be effective when you have a patient in front of you, they're suffering, they're not functioning, they're dealing with depression. By the time they get to you, they've been dealing with it for a while,  and then you tell them the treatment is going to take so much time to begin working. I don't know that that gives them much hope when it comes. I know there are many other things with that monoamine approach that we could do better. Can you give us some suggestions?

Jain: Yeah. The very fact that you're dissatisfied and I'm dissatisfied is quite important. Because status quo is damaging to our field. And more than half the patients who receive monoamine-based treatments are not where they need to be. The side effect burden is just profound. So why think differently? I think you articulated beautifully because patients aren't doing well. They want rapid onset of antidepressant activity. I will add one more thing to it, Brooke, which is in addition to rapid, they want a greater degree of improvement and they want it to come with less of a price tag, particularly sexual dysfunction and weight gain. So for all the reasons you have articulated, I'm also adding to it. We are desperately in need of not rejecting the monoaminergic approaches, but expanding above and beyond it.

Kempf: Above and beyond. I like that.


Rakesh Jain, MD, MPH, attended medical school at the University of Calcutta in India. He then attended graduate school at the University of Texas School of Public Health in Houston, where he was awarded a “National Institute/Center for Disease Control Competitive Traineeship.” He graduated from the School of Public Health in 1987 with a Masters of Public Health (MPH) degree. Dr Jain served a 3-year residency at the University of Texas Medical School at Houston. In addition, Dr Jain completed a postdoctoral fellowship in research psychiatry at the University of Texas Mental Sciences Institute, in Houston. 

Brooke Kempf, MSN, PMHNP-BC, has worked as a psychiatric nurse at Hamilton Center in Terre Haute, Indiana, since she graduated from Indiana State University with an associate degree in 1994. Her passion for mental health was sparked as she worked as a charge nurse on the Inpatient Unit and continued to grow as she served in their outpatient setting while obtaining her bachelor’s degree from ISU in 1996. She was awarded the 2008 Hamilton Award for Outstanding Staff Member. Kempf was then able to obtain her master’s degree from the State University at Stony Brook of New York and is board-certified by the ANCC as a psychiatric mental health nurse practitioner. She currently practices as the Hospitalist for the Inpatient Psychiatric Unit of Hamilton Center Community Mental Health Center in Terre Haute, Indiana and is an adjunct lecturer for IUPUI’s PMHNP program, teaching and was awarded the 2022 Daisy Award for Extraordinary Nursing Faculty.

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