Avoiding Misdiagnosis in Major Depressive Disorder

Too often, major depressive disorder (MDD) and treatment-resistant depression (TRD) are mistaken for other medical or psychiatric mimics, like thyroid issues or bipolar disorder. 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, discuss common pitfalls when it comes to diagnosing MDD and TRD, as well as tools that clinicians have at their disposal to hone their diagnostic skills and accuracy.

For more MDD and TRD resources, check out the Major Depressive Disorder Learning Library here on Psych Congress NP Institute Online.

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.

Dr Dambrino: So, we talked a lot today about pseudo-resistance with treatment resistant depression, and so many times when I am teaching, I will say across the board, your treatment is only as good as your diagnosis. What are some tools that we have as clinicians available to us to avoid that pitfall of misdiagnosis when it comes to TRD?

Dr Albright: I see this so commonly because some patients just get labeled with diagnoses flippantly, maybe in an ER setting or one time in an inpatient setting, and attention to detail and care is not paid to really decipher out is this depression? Is this bipolar disorder? Is this ADHD? Is this complex PTSD? Is this a medical issue? Unfortunately, I don't have any quick tips and tricks. We need to go back to the biopsychosocialspiritual model and evaluate every facet of a patient's life. We always need to start being clinicians medically first, rule out any medical mimics. I know in our talk we discussed some neurologic mimics, of course, thyroid is another one that can masquerade as depression. There are so many to discuss, but I would say it's the psychiatric mimics of major depression that make it most challenging.

I teach a lot of DNP students, we have a lot of new clinicians at my practice, and it's taken me years to really hone in on my diagnostic skills. You just have to see case after case after case. But I would say one way to expedite it is to speak with the family, obtain collateral from them, of course, with the patient's permission. I often have family meetings where the family come in. I love collaborating with the therapist, with the former psychiatrist if they've moved, for example, with the primary care physician just so that we can try to figure out, have they actually had a hypomanic episode before? Have they had a manic episode, or is this ADHD with TRD? Neuropsychological testing can also be very helpful for this. I would also add substance use disorders can often appear like treatment-resistant depression, but it's actually hidden substance use disorders and vice versa—folks that are withdrawing, they're detoxing, they can very depressed, and we need to give them time and adequate treatment to the underlying substance use disorder, first and foremost, while simultaneously treating their depression as well.

How do you approach it though?

Dr Dambrino: I think to your point, getting a really great history. The other thing is we can't forget to ask patients if they're actually taking their medication. Thank you. Because we, there are a lot of puzzle pieces and in fact, when we were presenting, this slide has a lot of information for a reason because we're sifting through a lot of information, particularly in a psychiatric evaluation. But I have started even more recently, again, I've been practicing for 8 years, but I've started really being conscientious about, are you taking your medicine? How many days are you missing on average per week? And sometimes I find out maybe they're not taking their medication 3 or 4 times. That's pretty significant. And so not asking that question, we can miss pseudo-resistance.

Dr Albright: We can.

Dr Dambrino: So that's a really important thing to consider.

Dr Albright: One other note, too, is I find too, especially psychiatrists that have been practicing for decades, they'll often diagnose TRD as bipolar disorder because there was nothing that adequately treated that patient's depression, and so they just labeled it as bipolar disorder. You might see they were formerly on lithium, a lot of atypical antipsychotic medications. I see that all the time, but then when you really sit down and talk with the patient and go through their history, they'll describe never having a manic or hypomanic episode, but this diagnosis just follows them. So almost once a day, a clinic day, I am taking away the bipolar diagnosis because there hasn't been a true hypomanic or manic episode, and that opens up so many treatment possibilities for us.

Dr Dambrino: Yeah, I find the same to be true. If you really ask those questions about, have you had hypomania, have you had any form, even cyclothymia, much of the time the answer can be no. And it is that kind of, okay, you haven't responded to these medicines, so it must be, which is not diagnostic.

Dr Albright: Or I see a lot of cluster B personality traits and they will describe having rapid mood changes hour to hour, day to day. And unfortunately, some clinicians will misdiagnose that as bipolar disorder, but it's actually more of a cluster B personality trait or a symptom of trauma.

Dr Dambrino: Right.

Dr Albright: Absolutely.

Dr Dambrino: 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 and 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.