Michael Edward Thase, MD: I think nonadherence or intermittent adherence is an inherent risk factor, that people who don’t adhere to treatment have less of a chance to get better. So you have to start at the top and ask are they really treatment resistant if they’ve not adhered to the treatment? This is one issue. I think other risk factors have to do with the amount of complexity and co-occurring conditions. We’ll talk about comorbidities a bit later. But the more complicated your condition, the harder it is for you to get better. This is partly because the lower your inherent chance of recovering is related to the comorbidities. I think other risk factors might include a comorbid condition like substance use and substance abuse. People who are drinking heavily or who are taking drugs, both prescribed and not prescribed, during the course of their depression are more likely to stay stuck in a depression. And some forms of depression are harder to treat than other forms. People who have an illness within the bipolar spectrum or those who either become suspicious or have delusional thoughts or hear voices when they’re depressed are harder to get better also.

Megan Maroney, PharmD, BCPP: True. What role does the Montgomery-Åsberg Depression Rating Scale play in diagnosing TRD?

Michael Edward Thase, MD: None, none in our practices. The Montgomery-Åsberg is the best, most precise 20-minute assessment scale for depression we have for our research studies. If we all had those 20 minutes to do that good assessment when we first met a patient in our practice, we would live in a nicer, more refined world. But we don’t. The one we do have enough time in our practices for is probably the PHQ-9 [Patient Health Questionnaire, 9-item depression assessment], which the patient typically fills out either the day of the visit at home or in the waiting room. The PHQ-9 conveys about 70% to 85% of the same information that’s in the Montgomery-Åsberg with a whole lot less clinician time involved. But the Montgomery-Åsberg is an excellent depression scale. If you see meaningful improvement on the Montgomery-Åsberg, you can be more confident that the person has had a response. Generally you need a 50% reduction in the symptom burden, and ideally that plus a level of depression symptoms that are way outside of the level expected with depression.

Megan Maroney, PharmD, BCPP: Definitely. You’re right. The PHQ-9 is much easier to use. It doesn’t require the person to be trained to be able to use it appropriately. Patients can self-rate their symptoms. Is that something you use a lot in your practice as well, Dr Skolnik?

Neil Skolnik, MD: Yes. The PHQ-9 is the only rating scale we use for exactly the reasons you said. I think the greatest value in using it is being able to track someone over time. While the literature supports its utility absolutely at the beginning, middle, and end of treatment, I think I can take a good history and gauge the level of severity of depression when someone initially presents pretty well. On the other hand, it’s almost impossible to track the level of severity over time because certainly as a clinician, I do not remember how a patient I saw 6 months ago was doing then. I think patients also don’t fully remember. They know they’re doing better or not as well as they would like. But it gives us that ability to have some objective consistent way of tracking symptoms over time.

Megan Maroney, PharmD, BCPP: Quantifying it, definitely. Dr Thase, besides the failure of multiple different treatments, what other factors might lead to a diagnosis of TRD?

Michael Edward Thase, MD: There’s a whole alternate view of this now that we should [describe it as a] person suffering from a difficult-to-treat depression as opposed to a TRD because the treatment-resistant term was borrowed from medical microbiology from 40, 50 years ago. And depression isn’t an illness like a bacteria is causing an infection, in that people are difficult to treat for a variety of different reasons, including their comorbidities and their adherence issues, and their histories of early trauma, and all these things. I think that it does require a good, comprehensive assessment with a biopsychosocial perspective on who the person is, how did they get into this circumstance, what’s been tried to help, and what’s gotten in the way of that. This is what you try to do in that first visit, sort out these questions, because depression is hardly a unitary condition. There are different kinds of depression, different presentations of it. Some people oversleep, some people can’t sleep, and so forth. I think one level is to record the treatments that have been tried, the doses, and whether they helped a little or not. How much trouble were the treatments from an adverse effect standpoint? This is complicated. But I think we make sense of the complications by taking the history and trying to understand how the person got there.

Neil Skolnik, MD: I certainly agree with that, and I’m so happy to hear you saying that. Depending on the person and their level of need when they initially present, I will sometimes begin treatment at a first visit. But I will sometimes say we need to figure this out and see someone back and not wait a long time, try to fit them in a week later, because a number of things go on in the office. One is trust. Many people will share more at a second visit than they do at a first visit because you build that trust. You’re also in a first visit with someone, particularly if it’s a patient you haven’t taken care of for years–I have some of my patients but others are new to me–I’m often surprised by what people share on a second visit that they don’t at a first.

For me from a practical point of view, and it’s both diagnosis and treatment I’m talking about here, it’s understanding what is going on in order to have a sense, as Dr Thase was alluding to, everyone’s depression is different. In some people, it’s kind of coming out of the blue. Maybe that’s more biologically based. Some people are under enormous stress. Some people have very clear cognitive distortions that they share. They worry they did something wrong at work and now their whole life will be in shambles, catastrophic thinking. Depending on where you fit with those depends on the potential value of CBT [cognitive behavioral therapy], for instance in the latter case, and how valuable therapy may be. Or if someone has no time at all to go to therapy, weighting medicines over therapy is an initial approach.

Megan Maroney, PharmD, BCPP: Dr Thase, is the diagnosis of TRD fluid?

Michael Edward Thase, MD: Yes, you can get to a spot where someone might say you have TRD at one moment in time because it’s not really even a diagnosis. Your diagnosis is depression. The treatment-resistant part of it is a description of your illness history. If you come in for treatment, meet the criteria [for TRD], but by your next appointment you feel way better on that, you come out of the depressive episode, you no longer have TRD. Yes, it can be fluid. Again, it’s not a diagnosis. It’s a description of the recent treatment history for the patient with the diagnosis of depression.

Transcript edited for clarity.