NP Notes: Development of Treatment-Resistant Depression (MDD Episode 4)

Craig Chepke, MD, DFAPA: Hello and welcome. I'm Craig Chepke. I'm a psychiatrist in private practice at Excel Psychiatric Associates in Huntersville, North Carolina, and also the Scientific Director of Psych Congress. This is the Great Exchanges in Mood Disorder podcast. I want to welcome my guest today, Dr. Margaret Emerson. Margaret, can you tell us about yourself?

Margaret Emerson, DNP, APRN, PMHNP-BC: Hi, thank you so much for having me. I'm excited to be here. I am a Clinical Associate Professor at University of Nebraska Medical Center, and I do a bit of research as well as practice in the integrated environment using digital technology to treat those disorders that are coming into primary care. So, thank you for having me.

Craig Chepke, MD, DFAPA: Fantastic. So, today, we're going to narrow things down from major depressive disorder in general to really hone in on treatment-resistant depression. And so, tell us a little bit about, what is treatment-resistant depression or TRD?

Margaret Emerson, DNP, APRN, PMHNP-BC: So, Craig, as you know, there are some, there's not a universal definition of this particular diagnosis, but it really comes down to the aspect of the trials of medication. And, typically, what we see is that individuals that are looking at treatment-resistant depression have failed at least two antidepressants. And then, also that they've failed those antidepressants for after they've been on them for an appropriate amount of time and the appropriate amount of dosage. Now, that varies a little bit too, so it creates a little bit of a muddy water situation. But we know it's folks that have had treatment that has been determined to be what we would expect to be expectable or effective, and they've had it more than once. And so, that's kind of—one of the issues that we see with treatment-resistant depression is that there are potential for the definitions to really impact what we are doing with this particular disorder.

Craig Chepke, MD, DFAPA: Right. So, I'm going to have to go off on a couple of my rants though here, Margaret. So, first, is that one of my crusades is I want to stamp out the use of the word “failed” in the way that we normally do it in psychiatric practice or in medical practice, really. That we say that very commonly because that's what we heard in training. It's what is in all prior auths that the patient has failed medications. And, to me, that's blaming the victim because it's not the patient that's failed the medications. The medications have failed the patient. And we intend it as a neutral medical jargon term. And I just put myself in the shoes of someone with lived experience. And think, if I heard my healthcare provider talking about me failing medications, that little voice inside my head from the depression speaking saying, “Oh, even my nurse practitioner, my doctor, they think I'm a failure, too. I knew it.” Because of that misperception and the cognitive distortions that people with depression so commonly have. And so, whenever I hear that, I just have to stop the conversation and go off on that rant.

Margaret Emerson, DNP, APRN, PMHNP-BC: So, I completely appreciate that you identified that because that is a conversation I have with patients. Because they’ll come in and say, “My doctor said I failed all these things. I have medication failure.” And I exactly use a very much a similar approach of understanding that it has nothing to do with their failure and their depression is not treatable. It really has to do with what we've selected for them has not been beneficial for them. And so, we need to really think about have we accurately diagnosed what was going on? What are the other contributing factors? Because, again, that will shape what we're going to be doing. So, I'm really glad that we're all having these similar conversations with patients because it is so important that they don't give up hope because that's a big factor in our success and our work with them.

Craig Chepke, MD, DFAPA: Absolutely. The hope is that—another one of my sayings is that the most important thing a provider can give a patient is not a prescription but hope.

Margaret Emerson, DNP, APRN, PMHNP-BC: Yeah.

Craig Chepke, MD, DFAPA: And the terminology treatment-resistant depression makes it sound like it's a terminal diagnosis. That's another frustrating aspect to me is that if they hear that, or even if they don't hear it from us, they go home and they look things up and they see, “Oh my gosh, I have treatment-resistant depression. I'm never going to get better.” And that just means the treatments they've been on so far have not been effective. And, historically, those treatments have all been monoamine based generally. And so, I kind of like the term monoamine-resistant depression or monoamine reuptake for resistant depression, something like that. But I want to circle back to what you mentioned about the diagnosis being so important. Because that is something that I think we need to pay a lot of attention to that even though we are psychiatric providers, we cannot ignore the potential medical factors that our patients are dealing with. And working in integrated care as you do, tell us about that. What are some things that can be going on medically that can be mistaken as treatment-resistant depression?

Margaret Emerson, DNP, APRN, PMHNP-BC: So, I'm glad that you bring that up because it's pretty commonplace for us to see a lot of depression and medical comorbidities. But the things that I look for are, how have things been going in terms of their overall wellness? So, how are they proactively managing some of their physical health? What sort of comorbidities do we already have at play for medical conditions such as sleep apnea or high blood pressure or thyroid conditions? Really looking at what's been established, what do we know about? And then, what have we missed so far? Are there things that we haven't really adequately worked up to make sure that we're not dealing with any of those factors in terms of symptoms that we're seeing with depression? So, it's kind of this back and forth of conversations with primary care providers and with patients and really understanding what have they done, what's been successful, and what have we missed? And making sure that that drives our ability to kind of really hone in on what we need to do diagnostically to assure that what we're seeing and what we think we're seeing is in fact the case.

Craig Chepke, MD, DFAPA: Absolutely. So, medical workups are very important. The one that I remember is, from medical school, was hypothyroidism. Like, oh my gosh, you got to screen everybody for hypothyroidism. And, statistically, that's still not all that common among people with MDD. However, obstructive sleep apnea, which you mentioned.

Margaret Emerson, DNP, APRN, PMHNP-BC: Mm-hmm.

Craig Chepke, MD, DFAPA: Estimated that about one out of three individuals with MDD can have obstructive sleep apnea. The American Psychiatric Association guidelines for treatment of patients with depression states that any patient with depression, if they have sleepiness, fatigue, or treatment resistance should be worked up for obstructive sleep apnea.

Margaret Emerson, DNP, APRN, PMHNP-BC: Mm-hmm.

Craig Chepke, MD, DFAPA: So, very high yield. So, I'm very glad you brought that up. Because it is missed very commonly in psychiatric practice because one out of three, as high as one out of three, may have obstructive sleep apnea.

Margaret Emerson, DNP, APRN, PMHNP-BC: And I'm sure you do this, Craig, but one of the things that I ask the patients are if they have obstructive sleep apnea, they have their machines, when was the last time it was tested? Are they wearing it? Are they wearing it the way that they're supposed to? Because that all will shape whether or not all the interventions that I'm providing are going to even be effective. If we're really dealing with somebody being fatigued and having sleep deprivation or not getting enough oxygen at night, that's going to affect their next-day functioning. So, it even comes down to those very little details that you can have a CPAP machine at home, but if you're not using it because it's broken or because you just don't like the way that it keeps you awake, those are things that we need to triage and figure out how to be creative in managing them for sure.

Craig Chepke, MD, DFAPA: Yeah, or if we see that someone has hypothyroidism and they are prescribed thyroid replacement, are they actually taking it? Are they taking it the way they're supposed to? We can't make those kind of assumptions that, oh, well, so that's being managed. Well, is it? It's been identified, but is it actually being managed? We have to ensure that as well.

Margaret Emerson, DNP, APRN, PMHNP-BC: Yeah.

Craig Chepke, MD, DFAPA: But, back to the kind of bread-and-butter issues of TRD. Talk to us about the treatment options available for TRD.

Margaret Emerson, DNP, APRN, PMHNP-BC: So, we are seeing more opportunities and options for treatment-resistant depression. We see antidepressants are kind of that mainstay that are going to in some way probably be a part of this. We're seeing, again, that influence of the idea of having psychotherapy be a component of this. Psychotherapy on its own is probably not going to hit some of those more severe and moderate cases of treatment-resistant depression. But it is certainly something that's been demonstrated to be efficacious in conjunction with antidepressants, especially because we see trauma being a big piece of treatment-resistant depression. And so, the focus of some of those psychotherapies can also hit some of those aspects of trauma that are impacting the depression that we're seeing. There's also atypical antipsychotics that we see as augmentation strategies that have some FDA approvals for those instances. And then, we have other brain-stimulating sort of modalities such as TMS or ECT. So, those are the things that kind of come off of, you know, that top of my head in terms of options for TRD.

Craig Chepke, MD, DFAPA: Yeah, so I want to push pause on this part of it because I want to circle back. You mentioned trauma. I want to dig into that just a little bit before we go back to some of the other treatment options and how we can manage those. That, I think, is incredibly important. And I wanted to get your take on how are you assessing for trauma and are there other psychological or socioeconomic influences on TRD?

Margaret Emerson, DNP, APRN, PMHNP-BC: So, this is one of the things that I think is pretty incredible in terms of assessing kind of that full patient. So, I work in primary care, as I mentioned, and one of the things that I will, because I have an hour with them, if I'm doing a consultation. I get the time to ask them about if they've ever—what was childhood like for you growing up? What are your experiences with, have you ever been a victim of any sort of violence or any abuse situations? And they will have worked with their primary care for, you know, they are dedicated to these primary care providers. So, decades sometimes. And in that short period of time, I will have unmasked all of these different variable factors that have contributed to them presenting the way that they have. So, oftentimes, it can be a long history of trauma that they never really wanted to, I think, burden their primary care provider with because they're like, “Well, I know they only have 15 minutes.”

Margaret Emerson, DNP, APRN, PMHNP-BC: Like, “I can't unload this with them.” So, it's something that I've seen in clinical practice where having that additional time to figure out what's going on in terms of trauma and how that's contributing to stuff really affects what we're going to be doing. And it's so important because that changes kind of what the focus may be. So, it might be that we look at EMDR for psychotherapy or that we do more of that trauma-informed care with them and all those wraparound services, and that changes the game. So, maybe it's not about having treatment-resistant depression. It's about us understanding all the factors that go into what's at play and really addressing those from a very efficacious standpoint.

Craig Chepke, MD, DFAPA: Right. Because if they have a profound history of trauma or if they're currently in a traumatic situation, what is a medication going to do? How could it possibly work? And so, we've got to identify those factors. And I think having a high index of suspicion that if someone has TRD, we almost have to assume they have some kind of trauma until proven otherwise. Because, even though we do have more time, they still may not feel comfortable bringing up. They may have just learned to live with it. It's their new normal. I mean, how else could they have survived? Some of the patients I've worked with, how could they have survived the situations they were in unless they were able to just very strongly just put that in a box. And once something gets put in a box or swept under the rug, then sometimes they're hesitant to bring that back out.

Margaret Emerson, DNP, APRN, PMHNP-BC: And it's so funny that you use the box sort of metaphor because I always say to them like, “You can put it in the box, but eventually stuff starts eking out of that box.” And so, we do have to take our time and really look at how do we open that up in a way that's healthy for them, but also recognizes that it's still at play. Even though we're shutting it, it still has an ability for it to leak its way out and affect the things that we're doing. And it's so incredibly important.

Craig Chepke, MD, DFAPA: Exactly. Exactly. So, let's go back to talking about medications rather than focusing on specific agents, maybe just more generally. So, how can we help patients to navigate through switching antidepressants or augmenting? How do you deal with that?

Margaret Emerson, DNP, APRN, PMHNP-BC: So, what I typically do is really make sure that I understand the extent of what's already taken place. So, when a patient comes in and they say, “I've tried these medications, and I failed.” We have the conversation about what failure really is, and it's not a failure on their part. But understanding what medications they've used. What dose, how long, how were they titrated? And then, after they were titrated, how long did they stay on that medication? And what were—did they have any benefits from it? Did they have any side effects? Is this something that anybody in their family had tried, possibly. Just to kind of look at all the relevance, because those historical aspects are sometimes really hard to find in the charts. They are little details that may not stick out in somebody's note. And so, trying to get as much information from that patient as possible so I can really drive, what am I going to use next? And understand if I make an adjustment, is this a person that's going to be at risk for having withdrawal symptoms or really not tolerate backing off a medication and starting another medication without an understanding of those things. So, really seeing what that, what the play has looked like with the medications for that individual is so important because that shapes what you're going to be doing. And I'm sure you have a similar approach, too. Just really getting all that historical information from the patients, right?

Craig Chepke, MD, DFAPA: Yeah, I mean, I like to ask people, “What did you like about this medication? What didn't you like?” To try and elicit both sides of the coin. Because, usually, there'll be both good and bad with medications that people have taken. And finding out what their attitudes about meds are in general. I mean, it's often happened that someone will say, “This medication doesn’t work, isn't working for me anymore.” “Okay, well I'd like to switch you over to X, Y, Z.” “Oh no, you can't change this.” “Wait a minute. You just told me it wasn't working.” And so, making sure we understand what their relationship with the medication is. Is it something that, even though they think it's not working for them the way it used to, it's still a lifeline for them and just hasn’t—or maybe it’s, even if biologically maybe it's not helping, is there an emotional attachment that they have to it that could make switching hard? How do you decide whether to switch or to augment?

Margaret Emerson, DNP, APRN, PMHNP-BC: So, one, is that patient conversation. When folks are saying, “This has done nothing for me,” in that instance that you're referring to, then we talk about what are potential options. And if they're not completely adamant that I need to stay on that medication, then what I will do is I will decrease that dose a little bit to see what happens. Because some folks will say, “Well, it's not doing anything for me.” I decrease that dose just a skosh. And, all of a sudden, they're coming back and they're like, “Things are not going well for me.” And so, that really suggests to us that they've had a partial response. It is obviously not achieve remission, which is for everybody. We really do want people to get back to their baseline functioning or better if that would ever be possible. And so, looking at if we want to continue with that current medication, then at that point I would look at augmenting them. And discuss, “This is why we're thinking about adding on another medication is because clearly you've had a response to this, and it makes sense for us to consider adding another medication. How do you feel about that? What are going to be the problems with doing that? What are your thoughts about adding something, and is this going to impact your life?” And costs are always, that's always a part of the picture. So, really, it's about using the evidence that we have. And then, helping the patient know what the options are and helping them on that journey and letting them decide with you and not just saying, “This is what we're going to do.” And then, that helps the success, I think, for sure.

Craig Chepke, MD, DFAPA: Definitely. I love that question, “How do you feel about that?” Because a lot of times, patients say, “Does that mean I'm that sick, that I need more than one medication?” And I'll usually draw on a medical analogy of, well, if they have diabetes, say, and they're on multiple medications for diabetes or hypertension or whatever, that, “You're on two medications for your COPD. Does that mean that you're an untreatable, hopeless case of COPD?” Or of diabetes, whatever it is. And it's just that there's that stigma with psychiatric treatment that doesn't exist to the same extent in other fields of medicine. Of course, everyone wants to be on monotherapy for everything. But I think it's much more accepted to be on combination treatment for other conditions that it is accepted for psychiatric medications, unfortunately.

Margaret Emerson, DNP, APRN, PMHNP-BC: Right. And we know—oh, I'm sorry.

Craig Chepke, MD, DFAPA: No, you go ahead.

Margaret Emerson, DNP, APRN, PMHNP-BC: We know that depression, as we gain an understanding of it, that it may not just be a serotonergic activity. That we are seeing other neurotransmitters at play. And that really is something that we need to be open to and explaining to patients, “The reason why I'm thinking about this is because there are other neurotransmitters that we need to hit. And we need to make them available because that may help with some of those issues with not feeling like you want to get out of bed or dealing with not being able to get remission in symptoms.” So, that's all a part of that education that we provide for them, for sure.

Craig Chepke, MD, DFAPA: Absolutely. I think that education is unbelievably important because, you know, my kids don't want to be told, “Do what I say, because I say so.” My patients sure as heck don't want to be. So, education is so important, and people really want that. A lot of them, I find, really want kind of nitty gritty things. They want to hear about receptors and things like that. It increases their confidence in the treatment it seems, and it improves the relationship between them and me. So, I highly encourage providers out there, educate your patients on mechanisms of action.

Margaret Emerson, DNP, APRN, PMHNP-BC: Yeah, and ask those questions, “What sort of things have I covered? What things do you maybe have questions about or you might go look up later after this?” Because they are, they're doing that, and they're coming to the table with a lot of information.

Margaret Emerson, DNP, APRN, PMHNP-BC: I usually will ask patients before I start prescribing, “Is there anything that comes to mind for you? Have you looked up any agents that you think might be a good fit for you?” And then, understanding why they thought that that particular medication would be a good fit. Was it because they saw it on tv? Was it because they had a friend that responded well with it? Because all of that information can really help take some of that gray area that we have for all the different options and narrow the field and work with the patient, letting them know that, “You have a voice in this and I want to work with you.”

Craig Chepke, MD, DFAPA: A hundred percent. Totally agree. Well, this has been a great discussion, Margaret, and I really appreciate you being here. I want to thank everyone for tuning in today to the Great Exchanges in Mood Disorders, and hope to see you back on another episode.

Margaret Emerson, DNP, APRN, PMHNP-BC: Thank you so much for having me. It was lovely.