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Clinical Pearls

Using Comprehensive Management of TRD to Improve Patient Outcomes

Join Brooke Kempf, PMHNP-BC, MSN, hospitalist at the Hamilton Center, and Rakesh Jain, MD, MPH, clinical professor, Texas Tech - Permian Basin, as they discuss how clinicians can comprehensively manage treatment-resistant depression (TRD). In this discussion, they highlight the importance of early intervention, measurement-based outcomes, and exploring multimodal treatments beyond traditional antidepressants. Discover why careful diagnosis is crucial, how to leverage glutamatergic therapies, and the role of holistic methods like exercise and psychotherapy in improving patient outcomes. 

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


Read the Transcript:

NP Institute Online Learning Hub: What key clinical pearls can you share regarding the comprehensive management of TRD, and how can providers apply this knowledge in their clinical practice to improve patient outcomes?

Brooke Kempf, PMHNP-BC: Rakesh, I think our audience is hungry for little pearls to help them think on how we can best treat patients, particularly when talking about treatment-resistant depression. What I would like to share with my colleagues is the emphasis that treatment-resistant depression isn't the individual who has failed every medication. We have to think earlier in the process and really be thinking about multimodal ways to treat depression rather than the same thing over and over. We're excited about some new opportunities to do that, but also in order to monitor our patient's response to any type of medication, I think we need to use measurement-based outcomes.

Rakesh Jain, MD: Oh, well said.

Nurse Kempf: I don't think we do a good job of that. So that is one key pearl I would share with my partners that we want to measure. Our patients don't do a really good job of recognizing where they've come from, what they're doing, etc. It's hard for us to remember, but when you're documenting that progress, or maybe even in failure, you're going to be able to see the response and know you're on the right track.

Dr Jain: Yeah, I love that. Measurement-based care may be the lowest-hanging fruit in all of psychiatry, and you articulated why its importance is crucial. The other thing to make sure of is you're dealing with depression because about one-third to one-fourth of patients with what we call TRD, actually suffer from bipolar depression, so be sure of that diagnosis. About 10% of them actually have psychotic depression that's not going to respond to antidepressants, so watch for that. About 10% of them have a substance use issue, so we have to do a pretty comprehensive overview. The other thing perhaps is if you failed monoaminergic treatments, it's okay to break up. You don't have to be in a bad marriage. It's okay to ask for a divorce.

The good news is we have 2 different FDA-approved treatments; one is oral and one is an intranasal treatment option that is glutamatergic. Certainly for esketamine, the evidence is if you switch to a new antidepressant and add esketamine, which is glutamate, it turbocharges not just the quickness but also the degree of improvement. That's a good thing with dextromethorphan and bupropion combination. My experience has been even patients who failed monoaminergic medications actually do quite well seeing that response. And it's a big world. Right? So the way to go after glutamate is not just medications, physical exercise and meditation, Brooke, really have a strong glutamatergic signal.

Nurse Kempf: Don't forget psychotherapy.

Dr Jain: And don't forget psychotherapy! That's so well said. Psychotherapy is often thought of as non-pharmacologic, but it is biochemical also. So I completely agree with you. Your call to action, which is think big and think broadly sits really well with me when treating patients with TRD.


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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