Management of Treatment-Resistant Depression (TRD)

Andrew J. Cutler, MD: Let’s talk about a different patient population, Greg. What is treatment-resistant depression? We hear that term used a lot. What is your approach to treating these patients?

Gregory Mattingly, MD: We all have this group of patients. It’s this group of people I think of as having stubborn depression. These are the people who by definition have tried 2 or more antidepressants, they’ve gotten good courses and a good duration, and their depression just hasn’t gotten better. Most of my patients by the time they come to see me, a lot of them have already tried 2 courses of medicine. So 2 or more failures, adequate duration, and adequate dose, you truly took it and gave it a chance. The question is, what do you do next? We know for that group of patients, trying another standard antidepressant, the options aren’t going to be very good. Then we start looking at what are the novel treatment options. Sagar has brought up one, ECT [electroconvulsive therapy]. I think TMS [transcranial magnetic stimulation] would be another one, neuromodulatory. I think these newer medicines that modulate GABA [gamma-aminobutyric acid]/glutamate, such as esketamine or ketamine, are medicines…and I was part of those trials, saying could we move the needle in these people who have stubborn treatment-resistant depression?

Andrew J. Cutler, MD: Yes, that certainly makes sense. People also will try augmentation with atypical antipsychotics, as you mentioned. But as these newer options become more available with novel mechanisms, it only makes sense to me if you failed monoaminergic reuptake inhibitor–type medicines to try something totally different. It just makes sense, wouldn’t you agree?

Gregory Mattingly, MD: I think the other thing for that group of patients, and I’ll go back to Sagar, the way you do this, I try to inspire hope. “Listen, I have a lot of patients just like you. For most people I see, standard antidepressants haven’t worked very well. The good news is we have some newer treatment options that have been shown to work for your type of depression.”

Andrew J. Cutler, MD: Yes, that’s really helpful. I totally agree with you. And again, involving the patient and what their goals are, what does their definition of a good response look like? Because if we’re trying to do one thing and the patient is valuing something else, we’re at cross-purposes. Of course, we do have to talk about exercise and lifestyle issues. Sagar, your point about diet, not really having great antidepressant data, but the fact is that if people gain weight, they are more likely to be depressed. If they lose weight, they may be less likely to be depressed. We know that weight gain is associated with inflammation. We know that people whose BMI [body mass index] is 30 and above tend to not respond as well to traditional antidepressants. I always incorporate a discussion around that as well into what I do. We know that exercise does have some good antidepressant effects as well.

Sagar V. Parikh, MD, FRCPC: I wanted to add that I like Greg’s comment about restoring hope. We’re trying to do it differently, and by we, I mean another organization I belong to, the Canadian Network for Mood and Anxiety Treatments, CANMAT. We’ve produced treatment guidelines for many years now. We’re just about to come out with our latest set of depression guidelines, and based on patient advice, we’re not going to use the term treatment-resistant depression anymore because patients told us that it feels like a death sentence. It feels like, “Oh my God, I have treatment-resistant depression.” Imagine if you were told you have treatment-resistant cancer. It sounds like such a downer. So, we are changing the terminology to “difficult to treat depression.” We’ll see how the field reacts to that terminology shift, but we’ve found it valuable in talking to our patient advisers. We have patient advisers on our guideline committee, and they were pretty emphatic in saying that treatment-resistant depression is a very demoralizing term.

Andrew J. Cutler, MD: Thank you very much for that. I’m going to start trying to use that in my lexicon. I guess the abbreviation DTD [difficult to treat depression] might come more into our use.

Transcript edited for clarity