Considerations for Selecting an Antidepressant in Major Depressive Disorder

At the 2026 Psych Congress NP Institute, Kristian Dambrino, DNP, PMHNP-BC, Co-Chair, Psych Congress Elevate, shared practical, patient-centered strategies for selecting antidepressants in major depressive disorder (MDD). Speaking from her clinical and academic experience, Dambrino emphasizes individualized care beyond algorithms, highlighting the importance of defining patient-specific goals, monitoring early response, and prioritizing tolerability. She also discusses key pharmacologic considerations such as half-life, withdrawal risk, and drug interactions.

Key Clinical Takeaways

• In major depressive disorder, early response within the first 14 days—measured with tools such as the PHQ-9—is predictive of later response and remission, and lack of improvement in this timeframe should prompt consideration of switching antidepressants rather than prolonging ineffective treatment (eg, up to 8 months).
• Antidepressant selection in MDD should prioritize tolerability, patient-defined treatment goals, and the presence of anxious distress (reported in ~75% of patients), with ongoing reassessment to ensure improvement aligns with outcomes meaningful to the patient, including resolution of residual symptoms such as anhedonia.
• Pharmacologic decision-making should incorporate dose optimization (with low-to-medium doses often effective), antidepressant half-life (eg, venlafaxine 2–4 hours and associated withdrawal symptoms), and drug interaction risk, particularly in patients with polypharmacy.

Read the Transcript

Kristian Dambrino, DNP, PMHNP-BC: Hi, I'm Kristian Dambrino. I'm a doctor of nursing practice, practicing and living in Nashville, Tennessee at Dambrino Consulting and Wellness. I'm also adjunct faculty at Belmont University College of Nursing, and I'm a Fulbright Scholar.

Psych Congress Network (PCN): Can you walk us through a step-by-step approach to choosing an antidepressant for a new patient with major depressive disorder, including how you weigh tolerability, comorbidities, and patient preferences? 

Dambrino: So anytime I'm speaking to clinicians and I'm teaching or having conversations with my colleagues, we know that people cannot be reduced to algorithms. I tell that to my patients in the first visit every time, I'm like, look, this is an hour. There is no way in an hour that I'm going to have you figured out or that you're going to feel comfortable telling everything to me in an hour. You're not going to trust me in an hour. And almost all the time when I tell that to my patients, they will say, "Yeah, you're right. Frankly, I don't even want to be here." And they feel so comfortable that I've called that out in the room.

So, when we get that out of the way and hear individually, I'm always going to document in the electronic health record, what are the specific goals? I'll ask the patient, "What does improvement look like for you in depression? What do you want?" And then every time I follow up, I'm going to say, "Okay, you said this 4 weeks ago. How are you feeling now that you've been on this medication?" I'm always going to think about tolerability because if someone comes back to me and maybe they're not crying every day, they're no longer having thoughts of suicide, which is wonderful from a safety standpoint, but they are at their son's baseball game and they don't feel that kind of joy. They still have that breakthrough anhedonia. Is that really the improvement that they initially wanted? So, all of that. Tolerability goes into the choice of antidepressant. We need to know also the half-life, which ones are more likely to have withdrawal symptoms. Many patients are very worried about that. I'm always talking about the science of how long a medication is in your body, for example, just so that patients feel empowered to provide informed consent.

PCN: When a patient has an inadequate response to an initial antidepressant, how do you decide between optimizing the dose, switching, or augmenting—and what factors guide that decision?

Dambrino: So, when my patients, the longer that I've practiced, the more likely I am to pay attention to inadequate response because we know per the literature that delaying treatment and waiting too long—in our lecture today, actually, Dr Jain mentioned that in some of the research that he's done, he sees that people will stick with an antidepressant for up to 8 months. And you could hear the room kind of go, "Wow." And we know that to be true. I've done that before myself. I've worked with patients for years where I'll have to say, "You know what? I'm sorry. We should have moved faster on this. " Because the longer that we wait, it's harder to achieve response and remission.

That's why we look at that early period of the first 14 days and achieving at least some reduction in the PHQ-9 or whatever tools we're using to measure depression, because that's predictive of increased chance of response and remission. So, I'm paying attention to those first 14 days. I'm always checking with my patients during that time. And really, if we're not getting some movement, we're going to move to another agent.

PCN: What are the most clinically important pharmacokinetic principles—and common dosing mistakes—that clinicians need to understand to use antidepressants safely and effectively? 

Dambrino: So, there are a lot of misunderstandings that we have. In fact, I was taught in my graduate education to max out the dose of antidepressants. That is per the recommendation of the American Psychiatric Association. We're taught keep pushing that dose until you get a response when actually low to medium doses are typically most effective for treating depression. The other thing too is that we know that 75% of patients who have major depressive disorder also have features of anxious distress. So again, depression doesn't look the same in everyone. So if I choose an antidepressant that also has potential to help anxiety, that's very relevant.

Then, the other thing too is how long is the medication staying in a patient's body? Many patients that we see in psychiatry are already on multiple other medications. So we need to understand what is the interaction risk there, especially according to cytochrome P450 profiles, that and just having in your mind, okay, venlafaxine, for example, the half-life is 2 to 4 hours, so we know that's why patients will say, "Oh, I'm getting these brain zaps," that kind of a thing. But being able to translate that for the patient is really important. Translating that science so that the patient knows, "Oh, this is maybe why I'm feeling this,” and they're not personalizing why they may not be having that response, because it can take quite some time to really see that response.

The last point I'll make is we need to be looking for early improvement in those first 14 days of treatment, and that actually surprises people, but we need to see a shift in that period.

Thank you so much for joining me, and please be sure to check back for updates from Psych Congress Network.

Kristian Dambrino, DNP, PMHNP-BC, is an ANCC board-certified psychiatric nurse practitioner, and founder of Dambrino Wellness, an 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.

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