The Role of NMDA and AMPA Receptors in Rapid-Acting Antidepressant Treatments

In a series filmed at Psych Congress Elevate 2024, Julie Carbray, PhD, PMHNP-BC, PMHCNS-BC, APRN, and Kristian Dambrino, DNP, PMHNP-BC, dive into the future of depression and treatment-resistant depression (TRD) interventions. 

In part 1 of the series, Carbray and Dambrino discuss the role NMDA and AMPA receptors play in depression treatment and how they influence the efficacy of rapid-acting antidepressants. They compare these newer treatments to traditional interventions and underscore why rapid-acting options can be so impactful in the lives of those living with depression.

For more information and to register for this year’s Psych Congress Elevate taking place May 28th through 31st, visit the meeting website.

For more news and expert insights on depression, visit the MDD Learning Library.   

Read the Transcript

Julie Carbray: Hi, I'm Julie Carbray, nurse practitioner and clinical professor of nursing and psychiatry at the College of Medicine, Department of Psychiatry and the College of Nursing at the University of Illinois, Chicago. 

Kristian Dambrino:  And I'm Kristian Dambrino, a psychiatric nurse practitioner and founder of Dambrino Consulting and Wellness and I practice in Nashville, Tennessee. 

Carbray: Kristian, for a long time we had the monoamine hypothesis of depression. Essentially, there's not enough of a neurotransmitter in a synapse, so we're trying to use our medications by inhibiting monoamine oxidase, and then having more neurotransmission, say, of serotonin, of norepinephrine, sometimes dopamine, to try to affect depression. There's some promise with newer mechanisms of action working on neurotransmitters like NMDA, also AMPA. Tell us a little bit about how they might work and why they offer more promise of rapid treatment.

Dambrino: The issue or challenges with the monoamine hypothesis is really when we look at the timeframe of how long it takes for these medications to work. This could be 2 to 4 weeks, and when patients are having difficulty getting out of bed and having trouble in their relationships and things like this, we would really like to be looking at medications that hopefully would work more quickly. So when we're looking at the glutamatergic pathways of medications and NMDA and AMPA receptors, those are ionotropic receptors, and they open and close very quickly. That translates into the real-world picture, hopefully improvement that's quicker, maybe within days, sometimes within hours depending, and so it's a really interesting thing to think about.

I kind of compare it to the lights and the music of a concert and how they often can be coordinated, and if they're not, then the performer is really not showcased in an optimal way. We would actually conceptualize glutamate as the performer, and so AMPA and NMDA, when they're working optimally, there's neuroplasticity, there's synaptogenesis, there's optimal cognition and mood. So this is really a complex system but with the potential to have a more rapid onset. 

Carbray: I love that you brought in your being a musician into your conceptualization of what this looks like. This is not, pick up a baton and you have somebody playing. This is a whole concert with different components really impacting that neurotransmission, synaptogenesis that really can improve symptoms quickly. 

Dambrino: Right, because there's astrocyte involvement, there's intracellular involvement. This is not as simple as presynaptic, postsynaptic. And I think that is one of the biggest takeaways as well. 

Carbray: Yeah. Kristian, thank you so much for this great conversation about treatment-resistant depression and building hope for our patients about new mechanisms of action. 

Dambrino: Absolutely. Thank you. I've enjoyed meeting with you and I've really enjoyed learning as well.

Julie Carbray, PhD, PMHNP-BC, PMHCNS-BC, APRN, holds her PhD (93) and Master of Science (88) degrees from Rush University, Chicago and her Bachelor of Science (87) degree from Purdue University in West Lafayette, Indiana. A clinical professor of psychiatry and nursing at the University of Illinois Chicago and the director of the Pediatric Mood Disorder Clinic, she has been practicing as a Psychiatric Nurse Practitioner for over 35 years.

Kristian Dambrino, DNP, PMHNP-BC, is a board-certified psychiatric mental health nurse practitioner and the founder of Dambrino Wellness, an outpatient mental health practice in Nashville, TN. She received her Doctor of Nursing Practice from Belmont University College of Nursing, with a focus on innovative global nursing partnerships in Indonesia. Having worked extensively with severe and persistent mental illness in community mental health and crisis settings, Dambrino embraces a trauma-informed, evidence-based prescribing model for her patients.