Targeting Non-Monoaminergic Pathways in MDD and TRD Treatment

In this video discussion, Brooke Kempf, MSN, PMHNP-BC, hospitalist at the Hamilton Center, and Rakesh Jain, MD, MPH, clinical professor, Texas Tech - Permian Basin, dive into the emerging role of glutamate in the neurobiology of depression. Learn how this critical neurotransmitter is reshaping our understanding of depression, cognition, and mood disorders. Dr Jain examines why glutamate-focused treatments could revolutionize how we tackle treatment-resistant depression (TRD) and spark renewed hope for patients. 

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

Read the Transcript: 

NP Institute Online Learning Hub: Could you explain the role of glutamate in the neurobiology of depression, and how targeting non-monoaminergic pathways presents a new approach to TRD treatment?

Brooke Kempf, PMHNP-BC: Rakesh, I think probably 4 or 5 years ago, I began watching YouTube videos from you talking about how we need to get excited about glutamate and, as a profession, we really need to learn more about this and how we can use it in treating major depressive disorder. Of some of the things that come to mind that you've talked about, why is it important in the treatment of depression? We know when it comes to synaptogenesis and neuroplasticity, one of the things that you've recently taught me was the LCM, how glutamate can be important when it comes to learning, cognition, and mood. I can think about how this is going to bring about new treatment options for us, but I know there's so much more to glutamate and it's hard to summarize in a short time. What else can you add to this?

Rakesh Jain, MD: First of all, thank you for being excited about glutamate. Glutamate is the single most excitatory neurotransmitter in the human brain, and psychiatry has been very slow to embrace it. That's our loss because 40 to 50% of the human brain is glutamate, and depression is a big disorder of the brain. It's not like Parkinson disease where the pathology is quite limited to start with. Depression appears to be what I would call 'a large track disorder;' everything goes wrong when someone's depressed. If you look at the fingerprints of glutamate, they are all over depression, Brooke. So as you said, it's involved in learning depression leads to poor learning of what happened. It's involved in cognition. Depression is a cognitive disorder and disorders of memory and mood go hand in hand with depression. So glutamate is crucially important.

I couldn't do any better than the summary you offered, which is that it's not just to improve the symptoms of mood, it may actually correct the mood disorder. So as you said, synaptogenesis, regenesis, and most importantly, the improved neuroplasticity of the brain that glutamate gives may be the reason why the excitement about glutamate-based drugs is the greatest excitement I've seen probably in the last 40 years in psychiatry.

Nurse Kempf: How can you not be excited?

Dr Jain: You don't have a choice.

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.