This video is part of a 3-part series on “Current Landscapes of Major Depressive Disorder Therapeutics.”

View part 2 here: https://www.clinicaltopicsdepression.com/video/current-landscape-major-depressive-disorder-therapeutics-part-2

View part 3 here: https://www.clinicaltopicsdepression.com/video/current-landscape-major-depressive-disorder-therapeutics-part-3

Craig Chepke:
Hi, my name's Craig Chepke and welcome to Clinical Topics in Depression. I'm joined today by my colleagues Andrew Penn and Saundra Jain. We're going to have a discussion today about major depressive disorder. So current guidelines call for an 8- to 12-week trial of an antidepressant before we decide if someone has an inadequate response and then move to switch towards a different agent. That can be pretty long for patients, and we need to talk about how we can figure out what agents to use, given that guidelines don't really guide us very well in picking specific agents for patients. We're kind of left to just guess in a trial-and-error method. So Andrew, given the currently available information and available therapeutics, what extent do you look at things like adverse event profile, drug interaction profile, metabolic profile, comorbidities, to really pick what kind of treatments you think are going to be best for your patients?

Andrew Penn:
Yeah, your points well taken that there isn't a lot to guide us. We have treatment algorithms, but they often lump groups of medications altogether to say, start with an SSRI, for example. It doesn't say which SSRI to start with because data has shown that they're largely, roughly equivalent with the exception of side effects. So a lot of times I'm choosing based on side effects and past history. If somebody tells me that they did well on fluoxetine 15 years ago, that's probably where I'm going to start because we have evidence in that particular patient that that was a superior drug, or at least an effective drug for them. It may not be superior because it may be the only medication they've ever tried; but I would rather start with something that at least has some track record for that particular patient of efficacy than start out on my own.

Craig Chepke:
Yeah, I think it's funny. We have guidelines that don't guide us very well.

Andrew Penn:
Yeah.

Craig Chepke:
The APA guidelines for the treatment of patients with depression say that if a first antidepressant trial is ineffective, you can either raise the dose, switch, augment, add psychotherapy, use ECT, augment with atypical antipsychotics. Well that's everything.

Andrew Penn:
Right.

Craig Chepke:
That doesn't help us at all.

Andrew Penn:
That's the whole kitchen sink, right? Yeah. No, it really doesn't.

Saundra Jain:
I'm curious and want to ask both of you, for that 8-to-12-week period, how do you determine if it’s not been effective? What’s the role of measurement-based care in really doing the best job we can of knowing if it’s worked or not?

Craig Chepke:
That’s a great question because patients with depression are so notoriously unable to see their own improvement. I sometimes joke with them that the person with depression is the last person to know when things start to get better, because that hopelessness and profound negativity that we see with people with MDD, it gives them blinders that they can't see any sort of improvement. So I like to look at the family, if they have any, or friends coming to the appointments. I actually do a lot of family-based model because for that reason, gaining collateral information and also figuring out, are other people in their sphere seeing improvements that the person themselves are not?

And then measurement-based care. And that's a fantastic topic and you doesn't have to be necessarily a clinical trial rating scale. And one thing I like to do is just ask people before treatment, "What are three things you would do if I could wave a magic wand and your depression went away?” And then when they come back, even if they're saying that they're doing better, I go back to that list. "Well, have you got out your camera and taken pictures? Are you going golfing with your buddies? Are you playing catch with your son?" "No, no, no." "All right. I think we still got room to improve." "You might be feeling better, but there's still a lot of room for you to improve."

Andrew Penn:
And what I like about that question is that it starts to get to functional impairment.

Craig Chepke:
Exactly.

Andrew Penn:
Because what you're really asking there is, what have you lost as a result of your depression? And so if we could get those things back. And the other thing I like about is it invokes a little bit of hope at the beginning of if this medication were to work, what are some of the things it would allow you to do that you're not able to do now?

Craig Chepke:
Exactly.

Andrew Penn:
That's a question I sometimes ask.

Craig Chepke:
Yeah because it's not all about symptom reduction. It's about returning their life experience that they want back in their functionality.

Andrew Penn:
Absolutely. And this is something I've been thinking a lot of — especially with some of the psychedelic therapies — is that we're often looking at a change in the story that the person tells themselves about their illness. So, some of those symptoms may still be there. Some of that core features of the depression may still be there, for example. But the story that they tell themselves, and this goes to psychotherapy, when people have depression, they'll tell themselves that they're a failure or their lazy, or that they're incapable. And so is there a shift in that story is one of the things that I start looking for. And I also look for the family shifts as well, because sometimes a patient will tell me, "My wife heard me laugh yesterday for the first... She said she hadn't heard me laugh in a year."

Craig Chepke:
Right.

Andrew Penn:
Say, "Okay, that's a sign right there."

Saundra Jain:
I have a patient that I'm working with and he's an older gentleman, and just chronic depression. He’s been in therapy for, I mean decades, all sorts of medicine combinations. And my marker for when he is doing well and not doing well, in addition to measurement-based care, is his sense of humor. If he is joking and laughing, then I always comment, "You know that humor's still there. You may be doing better than you think."
And I wonder what you think about this. With measurement-based care, with depression, if you lose that quality of knowing how you're doing, measurement-based care offers a great way to engage patients in, "Well, I'm not really doing well." "Well that's interesting because on the form you filled out, let's just look at it for a minute." You begin to see clear improvements, or maybe they're actually doing better, but the story they've attached to is "My life is terrible. I'm going to always be this way." That sense of hopelessness, it's just so prominent.

Andrew Penn:
Right. Right.

Saundra Jain:
Yeah, I like that, Andrew.

Andrew Penn:
But this was always the challenge, was measuring depression. So if we were to have a quantitative depression level, serum level, blood level. So if somebody comes into our office, they're crying, they're anhedonic, we take a blood level and we come back and say, "Good news, you're not depressed." Right? What does that mean?

Saundra Jain:
What does it mean?

Andrew Penn:
It's meaningless, right? Well, what's wrong with me then? I mean part of the reason is depression's such a heterogeneous, probably set of diseases. It's not a single entity disease. So even if we had such a marker, it would probably be one of the other types that we don't have a marker for.
But it's similar to your point about measurement-based care is that you can start to break it down and say, "Okay, so it looks like your mood has gotten a little bit better, but your energy's still low. Or you're still not sleeping well."

Saundra Jain:
Or you're not sleeping well. Yeah.

Andrew Penn:
And I always warn patients that certain things are early to change, and then other things are often late to change.

Saundra Jain:
Right.

Andrew Penn:
So you have to look at those leading and lagging indicators of improvement. And that's part of educating patients is so that they know that what's happening at two weeks might be only the tip of the start of this improvement, and that at six weeks they might be significantly better.

Craig Chepke:
Yeah, I think it's a critical education always. I mean the most important thing a clinician can give a patient is not a prescription. It's education and hope.

Andrew Penn:
Absolutely.

Craig Chepke:
That we've talked about a couple times here, but educating patients that what depression is. We as clinicians know that there are the emotional cluster, the cognitive cluster of symptoms, the somatic cluster of symptoms, et cetera. But patients don't know that.

Andrew Penn:
Right. Right.

Craig Chepke:
So that when they say they're depressed, they're thinking, "Am I sad?"

Andrew Penn:
Yes.

Saundra Jain:
That's right.

Craig Chepke:
And their energy could have improved, they could be more motivated, their sleep might have improved, their appetite; but if they still feel sad and down, of course they're going to say, "My depression is no better," because their bounds of what they think depression is. They've not been educated the way they need to be.

Andrew Penn:
That's right.

Saundra Jain:
Well, and I'll make a pitch for measurement-based care again, because PHQ-9, really gold standard has questions that speak to physical, emotional, and cognitive. So it's not perfect. I'm not going to make a pitch for that. But in terms of really helping us with something more objective, it helps us not miss certain things, and also it's a great way to just engage with patients.