NP Notes: Underlying Pathology of Residual Symptoms (MDD Episode 5)

Craig Chepke, MD, DFAPA: Hello and welcome to the Great Exchanges and Mood Disorders podcast. I'm your host, Craig Chepke. I'm the medical director of Excel Psychiatric Associates in Huntersville, North Carolina, and also the Scientific Director of Site Congress. And joining me today is my fellow steering committee member on Psych Congress, Andrew Penn. Andrew, give us a little introduction to the audience.  

Andrew Penn, RN, MS, NP, CNS, APRN-BC: Hey Craig, thanks for having me. I'm Andrew Penn. I'm a psychiatric nurse practitioner. I'm a Clinical Professor at UC, San Francisco School of Nursing, where I divide my time between teaching psychopharmacology, doing clinical work at the San Francisco VA, and also research and rapidly acting treatments for depression, primarily psilocybin is our area of focus, and I have been able to know Craig for many years now as colleagues on the Psych Congress steering committee. So it's exciting to be here.  

Craig Chepke, MD, DFAPA: Yeah, we've had great presentations together, great discussions together, so I'm looking forward to it as well. So let's start off talking about residual symptoms in major depressive disorder. This is extremely common. And give us a rundown of what are some of the common residual symptoms and is that congruent with what you see in the field?  

Andrew Penn, RN, MS, NP, CNS, APRN-BC: Oh, absolutely. I mean, I think all of us who work with patients often have this. We have these little spiels that we have when we talk to patients about what to expect from a medication. And many of us with typical antidepressants are talking about you may only notice side effects of the first few weeks, and then you start to notice some benefit and then often your mood will get better first. That is one of the first things to get better. But then there's these things that are trailing symptoms or maybe even don't ever catch up and become residual symptoms. Those are things I think about anhedonia. I think about sleep. I think about some of the somatic symptoms that go along with sleep disruption, like just being tired or having physical aches and pains, and then sometimes it's difficult to disentangle what's a residual symptom from what's a medication side effect.  

So anhedonia is probably a really good example of that because I'm sure we've both heard from patients where they'll say, I don't feel as depressed, but I also don't feel much of anything. I used to cry in sad movies. I don't cry in sad movies anymore. And I'm just kind of feeling, I call it the “meh” effect. It's like, “Meh, I don't really care about anything. I don't feel depressed, but I also don't care about anything.” And so I think of that as both a residual symptom, but also sometimes a side effect of medications too, particularly our typical treatments like SSRIs.  

Craig Chepke, MD, DFAPA: Yeah, I like the way that you categorized it as the early resolving symptoms, the trailing ones, and then it's a blurry line to how long do you wait for those trailing symptoms. Yeah, they don't all resolve at the same time. And sometimes I think we can fall into the trap of, oh, their mood's better. They're saying they're better. They're thanking us all. Thank you so much. You've helped me and we hope and wish that these trailing symptoms are going to resolve, but they might not. And that's really where I think we have to be more vigilant. What do you do to make sure you're staying on top of assessing those residual symptoms?  

Andrew Penn, RN, MS, NP, CNS, APRN-BC: Well, I think we can't just stop with the first question, right? We can't just say, well, how's your mood? And somebody says, “Oh, it's a lot better.” I say, oh good. Lemme pat myself on the back. But really to make sure that we're asking those follow-up questions. I often, when I'm doing the initial assessment for depression, I do some frame-setting and say, now most people when they think depression, they think about mood. But I think of depression as this whole constellation of symptoms that includes things like your appetite and sleep and sexual interest and enthusiasm and energy levels and that's all—your ability to concentrate—that's another one that a lot of people don't really think about the cognitive effects of depression. And so similarly, so if we've sort of set that frame from the beginning, then it's an easy follow-up question to say, well, it's great that your mood is doing better, but tell me about, you said last time we met that you were really just not feeling enthusiastic about anything. Tell me more about that. How is that doing? How's your sleep? How's your appetite? Those kind of symptoms are really important to follow up on and not just stop with the mood is better, so therefore my work is done.  

Craig Chepke, MD, DFAPA: Yeah, absolutely. And just one thing that popped in my brain, another one that can be difficult to tell is that a symptom of depression or side effect is sleep because SSRIs are very REM-suppressing and they can have some profound effect in insomnia, could be initial, middle, terminal insomnia. That's another one. But definitely I think psycho-ed into the multifaceted nature of depression is huge because in society, in American culture at least, depression equals sadness more or less. And we as clinicians can fall into the trap of asking, like you said, that first question: “Well, how's your depression doing?” and assume that the patient understands that that means all of those multifaceted things that you mentioned. We've got to make sure that we're using the same language as they are.  

Andrew Penn, RN, MS, NP, CNS, APRN-BC: Yeah, absolutely.  

Craig Chepke, MD, DFAPA: And also you brought up very importantly, cognitive dysfunction, because that’s another one that the research has shown that a lot, everything you mentioned is common, but I think the more difficult symptoms to stamp out that are common residual symptoms are anhedonia that you brought up first and cognitive dysfunction. And unfortunately, those also correlate very highly with the dysfunction and disturbances in quality of life that our patients face. So what do you do when you get to that point that you've got some of these residual symptoms in major depressive disorder?  

Andrew Penn, RN, MS, NP, CNS, APRN-BC: Yeah, you know what's interesting is where I work at the VA, a lot of times the presenting complaint is actually problems with attention, to which people have made the assumption they have ADHD. And as we often train our residents and our students that ADHD is a diagnosis of exclusion. So, if somebody has depression and they're having attention problems, we treat the depression first and we see what sort of ADHD symptoms remain. So that inattention or cognitive challenges creates a differential diagnosis challenge because sometimes we're asking ourselves, okay, is this a residual symptom of depression or is this an underlying ADHD diagnosis that was eclipsed by also having depression symptoms overlapping with it? And so sometimes there's a re-diagnosis process that needs to happen there. Now that we've got the depression better controlled, is there an ADHD symptom of presentation or is this some residual symptoms of depression?  

And often history is quite informative of that as well. If somebody didn't have any kind of cognitive or attentional problems before developing depression, I tend to be less convinced that there's an ADHD presentation going on. Whereas if somebody comes in and tells me I had lots of problems in school and I was always being told focus, and then later in life I got depression, and then once their depression gets better, they're saying I'm still having problems focusing, then I think more about an ADHD diagnosis. So this is where really kind of taking a good linear history is important to understand what we might be dealing with. Whereas if somebody doesn't have those symptoms and they're saying, my mood is better, but I'm still having problems focusing at work and at home, because again, we're looking for multiple domains that then I start thinking, okay, might this be some residual symptoms of depression?  

Craig Chepke, MD, DFAPA: I love that case illustration you walked us through of a residual symptom in a differential diagnosis with the ADHD. Talk about some other differential diagnoses that you might consider when someone has various types of residual symptoms.  

Andrew Penn, RN, MS, NP, CNS, APRN-BC: Yeah, I mean obviously anxiety and depression are so co-related that they might as well be kind of symptoms of each other, right? It's always funny that they live in different zip codes in the DSM, but really I see them as kind of holding hands much of the time. 

And so sometimes what we are looking at, say with sleep, and again also in my population with a veteran population, we get a lot of PTSD. And so somebody might present with attention problems or with mood problems and a little deeper in the excavation comes some trauma that hasn't been discussed, and that might be part of what's causing the ongoing sleep problems. So again, really I think one of our colleagues, Chuck Raison is such a great interviewer, and every time I watch him interview folks on stage, I am always just studying how he does it. And I asked him once, he says, well, every time somebody answers a question, you have two choices. You can either kind of go lighter or you can go deeper and with your follow-up question. And if you wanted to be more interesting, go a little deeper.   

And so the way that plays out in clinical work is that if somebody says, well, I'm having sleep problems, we shouldn't assume we know what that is. Well, what kind of sleep problems are we talking about? Are we talking about trouble falling asleep, staying asleep? Just feeling like your quality of sleep isn't very good. Are you having nightmares? Are you doing any kind of unusual things in your sleep? Are you finding that things are getting moved around in your house that you weren't aware of doing? Like parasomnia type behaviors? Does your bed partner tell you that you stop breathing in your sleep? Might we need to do a little apnea, sleep apnea workup? So those are all things, so I don't assume I know what the person is saying when they give me a brief description when they say, oh, I'm having sleep problems. I should have a follow-up question. What kind of sleep problems? Tell me how they affect you and where do you notice them?  

Craig Chepke, MD, DFAPA: Yeah, so sleep apnea is one near and dear to my heart. I have obstructive sleep apnea myself and wear a CPAP. And so it's one something that I've always been on a crusade for clinically and educationally as well now that I have this disability. But I'm really interested that you brought up parasomnias because I was actually the other day having a conversation with a very world-famous narcolepsy researcher, Emmanuel Mignot at Stanford, and he brought up a study that he had trouble getting—he's a psychiatrist by training, went on to become a sleep specialist and practices sleep medicine at Stanford—and he did this large survey study and found a shockingly high incidence of parasomnias in people, in people with mental health conditions. And he shopped, not shopped it around, but I mean he submitted it to several psychiatric journals and had a hard time getting it published in psych journals.  

Andrew Penn, RN, MS, NP, CNS, APRN-BC: Interesting.  

Craig Chepke, MD, DFAPA: And thought psych providers would have no reason to want to read about parasomnias, but it's very clinically important as you exactly just brought up.  

So that's fascinating. I'm glad that you did bring that up here. We can bring that to light. Sleep education, sleep-wake and circadian rhythm is very important to psychiatric clinicians and something we can really improve our patient's outcomes by considering. So that's why I love bringing you on, Andrew. You have the, just a different perspective on things that is just so incisive and so beneficial. And also, I was thinking as you were talking that the differential diagnosis can lead down a rabbit hole. So you've got with the sleep problems lump: Is it parasomnia? Is it PTSD? Is it sleep apnea? Could it be something else as well? Could it be bipolar disorder? We always have to wonder about that in people with depressive illnesses. Are they having more trouble sleeping after the antidepressant than they did before? Are they more irritable now and things like that. There's so many different things. When we see someone with residual symptoms, we've got to really stop and reconsider, what are we doing? Are we doing something wrong or do we have to take it to the next step?  

Andrew Penn, RN, MS, NP, CNS, APRN-BC: Right, right. Yeah. Because well, anytime as a clinician…we always have sort of a working theory where we have a hypothesis. My hypothesis is this is major depression. So scientific method: How do we test that hypothesis? Well, we start presumptively treating for major depression. Now, you have to be careful with this because, for example, lots of people come to us and say, “You know, I'm going to confess something. I took my roommate's Adderall for a few days and, oh my gosh, I did so much better in school. I think I have ADHD.” And whereas the reality is that most people's performance will improve to some degree with stimulants. So that doesn't necessarily make the diagnosis, but with we should always, I talk to my students about this idea of this sort of Bayesian thinking, you make a working hypothesis. I think this person, these symptoms, this constellation of symptoms equals depression.   

So I'm going to presumptively start treating depression, and then something new comes into that, into the hypothesis. Now, a week into the antidepressants, they're calling me and they're telling me they can't turn their brain off. They can't sleep. They're doing a whole bunch of stuff. And I need to go back and revise that hypothesis, right? Because now I'm thinking, oh, what's entering this possible hypothesis, bipolar disorder? And start thinking, do I need to change my treatment plan as a result of this? At the very least, I probably need to stop what I was doing before, put the brakes on. Okay, I'm going to have you stop taking that antidepressant. And then I'm going to think, okay, do I need to rethink my strategy here and go towards a mood stabilizer or an atypical antipsychotic? Something like that. But we’re always, we do an assessment at the beginning of treatment, but assessment isn't a one-time thing.  

We're actually always assessing even in ongoing treatment because people change, situations change, symptoms change. And I'm sure we both had patients that we treated for years thinking they had major depression, unipolar, or major depression. Then one day they had a manic episode and like, whoa, okay, didn't see that coming. Does it mean that you did everything wrong before? No, you did the best you could with the information you had at the time. You go back and you revise your hypothesis. Now, what would be a mistake is to not do anything differently. But as long as you step back and you say: Okay, well things have changed. We need to rethink our strategy. That's fine. None of us have the ability to predict the future. And so the important thing is to just always be reassessing and thinking about how might this be changing and what do we need? Most importantly, how do we respond to this to improve their functional wellbeing? Because at the end of the day, clinicians care about diagnosis, patients care about getting better. Most of them don't really care what we call it, just as long as they feel better. That's what they want. And so that to me is always the bottom line. Is this person able to function better in their day-to-day life with their family, in their work, in the school, whatever it is that's important to them? Are they able to do that better than they were before they met me?  

Craig Chepke, MD, DFAPA: So if I can summarize what we've talked about today. So first setting the framework of psychoeducation. What is major depressive disorder and the raft of symptoms. Make sure the patient understands the extent of what MDD can do. And then as the treatment progresses, make sure that we are being proactive in assessing for those residual symptoms. Make sure we're specific about it. And then if we do encounter them, let the patient lead the way with what are their residual symptoms and make sure we're considering a differential diagnosis as well, both psychiatric and medical. And I love the last thing that you had said is that we're always assessing our diagnoses. The way I think about it is that all psychiatric diagnoses are provisional because we don't have biomarkers, we don't have CAT scans, MRIs, DNA tests.  

Andrew Penn, RN, MS, NP, CNS, APRN-BC: Biopsies.  

Craig Chepke, MD, DFAPA: Biopsies. Anything that can tell us a definitive diagnosis. And so we should always be assessing, do we have the right diagnosis? No one's diagnosis is ever set in stone.  

Andrew Penn, RN, MS, NP, CNS, APRN-BC: No, it's not.  

Craig Chepke, MD, DFAPA: So I love this conversation, Andrew, and one, thank you for being here today.  

Andrew Penn, RN, MS, NP, CNS, APRN-BC: Thanks for having me, Craig.  

Craig Chepke, MD, DFAPA: So and thank you for the audience listening to this episode of the Great Exchanges and Mood Disorders.