This video is part of a 3-part series on “Current Landscapes of Major Depressive Disorder Therapeutics.”
View part 1 here: https://www.clinicaltopicsdepression.com/video/current-landscape-major-depressive-disorder-therapeutics-part-1
View part 2 here: https://www.clinicaltopicsdepression.com/video/current-landscape-major-depressive-disorder-therapeutics-part-2
So, there's several real problems with diagnosing depression, right? First of all is screening. So if you're talking about general populations, the people that come to see us, they've usually often already been diagnosed, but I'm talking about primary care. So, picking up depression when it happens, and then identifying who is at risk for it is one real challenge. And then of course is the issue of misdiagnosis. So depression is a real heterogeneous disease. Some people are anxious, some people are exhausted. They both have depression. So, when we're making that diagnosis, often we can miss things such as bipolar disorder or PTSD that masquerades as depression. So that's a real issue. And then there's a question of response. So we know that when people start responding more rapidly, when I was in training, we'd say, "Don't even look for a response for four to six weeks." And now in recent years said no. People that actually start saying, "I'm starting to feel better,” within a couple of weeks that's actually predictive of a good outcome.
Craig Chepke:You bet.
But here's the problem, right? Well, so the other people that are four to six weeks in, do we wait? Do we switch? No. You're three weeks into this, not showing a lot of response yet. Do we stay on this ride? Or do we switch to another one? Because it might work later, but we could be wasting time if it's not going to work. And the longer that depression goes on, probably the harder it is to get it to respond. And so these are all real challenges.
And then of course, the targets of our drugs are neurotransmitters that comprise a fairly small proportion of total brain neurotransmitters. Serotonin, dopamine, norepinephrine, those are all our usual target; but there's so much more than that. So there's a lot on the plate here.
I was going to say, there's a lot of meat on those bones.
Let's start with diagnosis. So, if I'm a primary care provider, how can I better pick up depression in my patients? Saundra, I think this speaks to a lot of the work that you've done with measurement-based care.
Saundra Jain: Oh, absolutely.
Andrew Penn: And screening.
Absolutely. As you were sort of laying out the challenges we face with diagnosis with MDD, that's the first thing that comes to mind. Because we all know that when patients come in with what we would consider to be a depressive episode, it is quite common that they actually have bipolar disorder, but they come in in a depressive phase of the illness.
Andrew Penn: Of course.
I mean, how often do we see hypomanic and manic presentation in the office?
Craig Chepke: Outpatient, never.
Saundra Jain: Never, right?
A supervisor once told me that your patient with a bipolar disorder, they'll see you when they're depressed. When they're manic, they might see the sheriff, but they're not coming see a doctor if they're manic.
Saundra Jain:That's right. I mean that's so true.
Because we're just going to rain on their parade.
Craig Chepke: Bingo.
Saundra Jain: Yeah. Right.
Andrew Penn: Yeah. Exactly.
So the way I try to approach that in terms of my own practice, and then just teaching and talking to colleagues about why measurement-based care matters is, okay, if we're going to use... I'll just use PHQ-9 again, because that's what we've been talking about. Marry it with another screener. Marry it with MDQ or bipolar spectrum diagnostic scale, all free public domain, easy to use, easy to score. Just because what looks like depression may not actually be depression.
And again, it's this challenge of that old saying about putting the cart before the horse, and this whole idea about timing and how long to wait. But sometimes, in terms of diagnosis, particularly in this arena around depression and bipolar, sometimes it's not as easy as first visit. “Oh, I did a really good history. I know what I'm doing.” I mean, how many times have you had patients? I can think of many where, oh, we just thought we were treating and we just thought we were right diagnostically. And then a person will say, "I've decided I'm going to go try to find my adoptive parents."
Okay, they might be in... I'm speaking of a particular woman in her late sixties. She found the history. And when we were given the history, we just went, "We missed the boat." Because this was a bipolar presentation and a person who didn't come in very frequently—coming in during depressive phases. And that was really one of our eye-opening moments when we were like, "We've got to do something differently." And measurement-based care sort of landed in our laps out of necessity.
Yeah. Yeah, absolutely.
Well, and the diagnosis of depression is just really kind of, the major depressive disorder, is a mess. I mean the history of it is that it in DSM-III, they cherry picked pieces for manic depressive illness, combined that with neurotic depression, combined with a little piece of melancholic depressions, mushed it into the category of MDD, and they have to meet five out of nine criteria. You do the math, that's 227 different ways that you can have the same diagnosis. You can sleep too much or not sleep enough. You can eat too much or not eat enough. It makes no sense. So of course we're going to have trouble diagnosing it because it's really clearly, as you've said over and over again, Andrew, it's heterogeneous. It's not one illness. It is a combination of many syndromes that we're just not smart enough yet to tease out which is which, and so we lump it all together.
And for primary care, you've got to look for it. You're never going to find what you're not looking for. So routine usage of measurement-based care is the key. Not just, "Oh, I have a suspicion this person has depression, so I'm going to give them a PHQ-9." You give it to everybody because it's going to surprise you. People are often afraid to talk about depression. They think it's weak, it's a personal flaw.
Saundra Jain: A stigma.
They think they should get over it. Or maybe they're presenting with more cognitive and somatic symptoms, and less of the emotional symptoms; but they still have major depressive disorder and they just don't feel that same... They don't feel what they think depression is like, and so it never crossed their mind. They're not trying to conceal it in some instances. They just don't understand. So we've got to consistently screen in primary care if we're going to catch the patients that we're missing right now.
So let's say we've caught the patient and we've made a diagnosis that we feel pretty confident in, pretty sure this is MDD. Is there any kind of biomarker that I can use to help me decide on what treatment to use? Is there anything we can send? We're getting labs anyways, hopefully, just making sure they don't have hypothyroidism or anemia. Is there anything else I can add to that that would help me choose a medication?
Well, first off, those are great points right there. And I think also educationally from a patient perspective, that kind of hammers own, that look, there is a biological component to this. If they are feeling the stigma of depression, that it's a moral failure or a weakness that, well look, there are things that are physical like the thyroid levels, iron levels. So that in and of itself is great. On top of that, I've recently been getting CRP, C-Reactive Protein. There's been more and more studies that have looked at that, including the CO-MED study, combining medications, antidepressants. And what was found is that people with a low CRP, low levels of inflammation, they actually tended to do better on a SSRI. And people with a CRP higher than one, they did better on a combination of SSRI and bupropion, a norepinephrine dopamine reuptake agent. If you put everybody together and didn't look at that, it was all dead even. But once you found that biomarker, it actually showed some differential outcomes. And that's been replicated a couple of other times. You were talking, Andrew, about nortriptyline.
Nortriptyline also being a noradrenergic agent was preferential for people that had a CRP greater than one. So having some level of increased inflammation, which of course is probably will turn out to be a depressive subtype. That will probably be. There will be an inflamed type of depression that maybe will respond more to a noradrenergic agent, rather than a serotonergic one. Well also, if it's an inflammatory type of depression, what about trying to reduce inflammation? I mean that's a lot of what you've done, Saundra, really, really well. Tell us about that.
Yeah, well I think when we look at wellness enhancing practices, we could look at exercise, which we know from the data.
Craig Chepke: Bingo.
I mean decades of data that we probably couldn't read in our lifetime. All the studies showing the powerful impact of exercise on depression. So, we look at exercise. We look at mindfulness meditation; we look at optimized sleep, optimized nutrition, and really the one that's coming to the forefront, we're really realizing the power of social connectedness.
Craig Chepke: You bet.
I heard one of our site congress faculty say that, he said, "This is a bold statement, but I'm just going to say it. Our brains are wired to be social."
Andrew Penn: Oh yeah. Absolutely.
Right. I mean, it's just so simplistically and beautifully stated. But you look at the literature and all of those practices, even positive emotions are anti-inflammatory. And so when we have all those things available to us, why not? Why not make those recommendations? So I think wellness is something that we want to elevate to the treatment planning table, along with what we're already doing. I think we'll have much better outcomes.
Yeah. And using WILD 5 in my practice, I bring in incrementally because sometimes I tell somebody who has bad depression that to do all these things, it feels overwhelming. "So go ahead, pick one. Let's start with one and next time we'll add another, and we'll just a little more at a time."
Saundra Jain: Baby steps.
Andrew Penn: Baby steps. These are all complimentary ways of attacking the problem.