Clinical Insights: First Case Analysis of MDD


Experts use a major depressive disorder (MDD) patient case to provide clinical insights on managing MDD, and how they would educate patients about their condition.


Gus Alva, MD, DFAPA: I love this entire dialogue about how to incorporate hypothetical, hypothesized, mechanistic views, but now really seeing them applied to the real-world setting based on some of the molecules that we have at our disposal right now. With that said, it might not be a bad idea for us to take a look at a couple of clinical case vignettes and maybe see how you might approach them with all this new information that we’ve been sharing with our audience. So why don’t we take our first case? We’ve got a 45-year-old gentleman who’s been struggling with symptoms of depression for several years. He’s married, he’s got 2 school-aged children, and he works as a middle manager in a demanding corporate job. He’s got no significant medical history, but does have a family history of depression. His father and his sister both experienced similar mental health challenges. At the present time, he sought help from his primary care doctor, having experienced persistent low mood, loss of interest in previously enjoyed activities, and significant fatigue. He reported difficulty concentrating at work, reduced productivity, frequent absenteeism, and now his wife and close friends also noticed that he had become increasingly withdrawn and disengaged from social activities. So his primary care doctor diagnosed him with major depressive disorder [MDD]. First thing, does this sound like a patient that you guys see on a daily basis?

Erin Crown, MHS, PA-C: Yes, except we don’t get a lot of treatment-naive or people very, very early in treatment in specialty medicine, and I think that’s true across disciplines for the most part. I think he sounds like a poster child for someone who would benefit from targeting glutamate as a primary mechanism of action. When you think about the middle manager, the stress, the home life…to your point, Greg, his brain’s been sick for a long time. It’s said years, right? He’s got cognition issues. he’s in the anhedonia that we talked about earlier. You brought up earlier [that could be] related to glutamate. So he sounds like a poster child for that.

Greg Mattingly, MD: When somebody’s depressed, and we’ve measured it in research studies, but processing speed has decreased 40%, imagine sitting at your desk and you’re trying to keep up with your colleagues and their brain’s working 40% quicker than yours. Imagine you’re a university student sitting in class and all of a sudden, your brain is working 40% slower than it should be. So his struggles are exactly what he said, and Erin, that’s why you know depression is the No. 1 cause of disability around the world. We live in a world that depends on cognitive capital.

Erin Crown, MHS, PA-C: And if you think about it, Greg, to your point of sitting at the desk and everyone else’s brain is working faster, if we go back to kind of what I was talking about earlier related to the interpersonal stuff, what kind of interference does that end up potentially causing in those work relationships? You know that’s just added stress and added inflammation. It’s all this snowballing cycle of effect.

Craig Chepke, MD, DFAPA: You can see why he’s withdrawing. We see that in people with hearing difficulties; they feel excluded, so they withdraw more. Cognitive deficits could be the same way. They feel like they can’t keep up, and so they’ll just stick to themselves, and they won’t join with the rest of the group.

Gus Alva, MD, DFAPA: Craig, I wonder if you might share with our audience how somebody like this, you’d help them not only understand their condition but the potential causes and then, subsequently, the available treatment options tied in with all of the themes that we’ve been touching on right now. Historically, what are the options that are available, having them have a better understanding of what they’re going through and what’s down the road?

Craig Chepke, MD, DFAPA: I think something I would really start with is making sure that they understand that this is a brain disorder, because one thing I didn’t hear a whole lot of in the case presentation was sadness and crying. There was some sadness there but predominantly it was the lack of function, the cognitive deficits, the social withdrawal, and those are things that the average person in America doesn’t necessarily associate with depression. They think of it as being sad and crying. They don’t understand the physical domain of symptoms of MDD, the cognitive domain of symptoms of MDD. So helping them to flesh out that picture with education that, look, this is this is part of the constellation of major depressive disorder, [but] this is something that is treatable. And with people especially early on in the illness, that’s the main message—exactly what you said, Greg, you got to give them hope. So I look them straight in the eye and say we’re going to get you better. We’re going to figure out a way, you and I together, we’re going to partner and find a way to get you better.

Gus Alva, MD, DFAPA: I am 100% listening to you as I’m thinking about this case. If you think about this guy’s own internal reflection, his self-image right now, I’m not keeping up, I’m not providing, I’m not taking care of my family, I’ve become a failure, I’m not the person I used to be. He gradually just shrinks into himself, and you can just see it happening. And we can predict where this case is headed, right, without intervention. Marital issues, starting to self-medicate, maybe starting to miss work, not showing up to work, maybe part-time disability, calling you for a job note, suicide. You can just see [it] kind of heading down [in] that cascade.

Transcript was AI-generated and edited for clarity.

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