Reconceptualizing Treatment-Resistant Depression as Monoamine Treatment-Resistant Depression

In this video taken at the 2025 Psych Congress NP Institute, Brittany Albright, MD, MPH, consultant, Psych Congress, and Kristian Dambrino, DNP, PMHNP-BC, consultant, Psych Congress, talk about the difference between major depressive disorder (MDD) and treatment-resistant depression (TRD). After discussing DSM-5 criteria, Drs Albright and Dambrino hone in on monoaminergic versus glutamatergic treatments, and consider why “monoamine treatment-resistant depression” may be a more apt descriptor for this patient population.

Read the Transcript

Kristian Dambrino, DNP, PMHNP-BC: Hey, I am Kristian Dambrino. I'm a psychiatric nurse practitioner living and working in Nashville, Tennessee.

Brittany Albright, MD, MPH: I'm Dr Brittany Albright, and I'm an adult and addiction psychiatrist from Charleston, South Carolina, and I own Sweetgrass Psychiatry. Kristian, you did a fantastic job during our presentation talking about major depressive disorder and also treatment resistant depression, and I would love for you to cover that material again. What are both of these states of illness and how do you differentiate them?

Dr Dambrino: So major depressive disorder, per the DSM-5, we need to have a depressed mood or anhedonia or both sometimes. We know too, we talked a lot in our session about how depression does not look the same in everyone. Now, treatment-resistant depression per the literature is typically defined as a failure of at least 2 or more antidepressants. It is important to also highlight when we talk about failure of treatments, we always talk about that in terms of the patient failing treatments, and I think that language really can be really harmful. I think that because we see that almost, per the STAR*D trial, almost 60% of patients did not remit on their first antidepressant. So what that tells me, and we've talked about this a lot, is that the treatment is failing the patient. So, changing the language around that in terms of treatment resistant depression is very important.

Dr Albright: What I'm hearing from you, so treatment-resistant depression, it's patients that have tried 2 or more oral antidepressants of adequate dose and duration, so at least 6 to 8 weeks, and those medications have failed, then that's TRD. So that's the majority of the patients I treat in my practice.

Dr Dambrino: Right. I know we talked about that too, and you could actually hear the attendees saying, yeah, that's absolutely what we see, because the medications that we've typically worked with are monoaminergic, and so there are definitely limitations there.

Dr Albright: So, instead of saying treatment-resistant depression, we should say monoamine treatment-resistant depression.

Dr Dambrino: Yes. There's this idea of, you've heard me talk about this too, tautology. So tautology is when we're talking about treatment-resistant depression or when we're talking about the monoamine-resistant depression, we're using the way that medications work. So monoamine reuptake inhibitors, we're using that to explain the pathogenesis of depression. It doesn't really explain everything. And in fact, I'd love to hear from you. I know we talked about just how many neurons in the central nervous system are actually monoaminergic versus receptors in the cortex that are glutamatergic.

Dr Albright: Well, I feel duped because I did my residency at Harvard and I thought, I'm being trained by the best and the brightest, and they truly were, but the reality is our science had not figured out depression then, and we still don't have it all figured out. But I feel upset now that I have learned that serotonin, dopamine, norepinephrine, these are often the neurotransmitters we're trying to modulate with SSRIs, SNRIs. They're only about less than 1% each of the neurotransmitters in the brain versus glutamate. It's the most abundant excitatory neurotransmitter. I am a business person, so I want to get the best bang for my buck.

Dr Dambrino: Yeah.

Dr Albright: Glutamate seems like that's where it's at because in the cerebral cortex it's around 85% roughly of the neurotransmitters.

Dr Dambrino: Right.

I'm Kristian Dambrino, thank you so much for joining us. We really hope that this was helpful and something that you can take back to your own clinical practice.

Dr Albright: I'm Brittany Albright. We appreciate the attention and we look forward to meeting you at one of the upcoming Psych Congress events.

Brittany Albright, MD, MPH, is a Harvard-trained, double board-certified adult and addiction psychiatrist and the founder of Sweetgrass Psychiatry, the largest physician-owned psychiatry practice in South Carolina. Dr Albright completed her psychiatry residency at Massachusetts General and McLean Hospitals, where she served as Chief Resident of Addiction Psychiatry. She now serves as an Affiliate Assistant Professor at the Medical University of South Carolina, where she also trained in addiction psychiatry.

A published researcher with over 20 abstracts and 15 peer-reviewed manuscripts, Dr Albright is a national speaker and consultant focused on innovative psychiatric treatments and clinician education. Her certifications in transcranial magnetic stimulation and psychedelic-assisted psychotherapy reflect her specialization in treatment-resistant depression and dual diagnosis.

Kristian Dambrino, DNP, PMHNP-BC, is an ANCC board-certified psychiatric nurse practitioner, and founder of Dambrino Wellness, an evidence-based outpatient mental health clinic in Nashville, Tennessee. As a Fulbright Scholar and Adjunct Faculty at Belmont College of Nursing, she is currently working on multi-site nursing partnerships in Indonesia and India that build nursing capacity and reduce mental-health stigma. During her Doctor of Nursing Practice program, Dr. Dambrino studied the impact of high-deductible health insurance on mental health treatment through a retrospective analysis, exploring how cost transparency between the provider and patient can mitigate financial decision-making for patients accessing psychiatric care.

As a national speaker and psychopharmacology expert, Dr. Dambrino regularly delivers continuing medical education programs at conferences across the United States. Her academic contributions include authoring accredited graduate nursing courses in psychopharmacology, guest lecturing at Vanderbilt University, and holding adjunct appointments at Michigan State University and Marian University.

Dr Dambrino is the creator of The Limbic Music, an R&B musical about neurotransmitters in mental health, currently in pre-production.

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