Steve Harvey, MD

The first question is, what is treatment resistant depression? So, when depression fails to respond to conventional treatment, then we call that treatment resistant depression (TRD). And beyond that very basic definition, it's only natural to ask yourself: “Well, how much treatment does it have to fail before it counts as TRD?” Right. So, if you look for a more precise definition or for a more fleshed out definition, it turns out that the definitions vary. Every place you go to has a different definition of TRD. The point here is that there is no consensus for a specific definition, and there's no universally accepted definition for what TRD is. As you'll see with these examples, there's differences in how many treatment attempts have to fail before you call it treatment resistance. Also, there's differences in parts of the wording [as well]. The definitions really vary.

How common is TRD? We just got through talking about how we don't have a precise definition, so if we don't have a precise definition, we sure don't have a precise percentage. But a very good rule of thumb is that it's roughly one third of patients with major depressive disorder (MDD) have TRD. Different people who have, you know, created estimates in different ways all come in at around that number. So, one out of three is just a very good rule of thumb. So, about a third of the people with MMD have TRD. With that many people with TRD, you know that anyone who practices mental health is going to have lots and lots of patients who they see who have TRD. The situation we see is kind of like this: You know, we see TRD all the time, every day. And I think so often that we hardly notice it sometimes because we're just we're just so used to it. Sometimes this can be the patient who comes in and says, "Oh, I'm doing fine." But when they say "fine," what they really mean is that they're not nearly as suicidal anymore. They are able to get up and go to work even though they're miserable, etc. Sometimes "fine" can still mean very depressed. Some of these people, you can give them a Patient Health Questionnaire (PHQ-9) and find out they're pretty darned depressed. We see these patients all the time who, even if they’re getting excellent care and the patient’s compliant and doing everything they’re supposed to do, [but] they’re doing lousy anyway. Of course, we all see that. Here we see, a lot of my patients just stay depressed: “This is fine.” The reason that this meme is amusing is because it's not fine. It's horrible for every individual with TRD; they are suffering. So, what can we do about it?

If a patient fails conventional treatment, what else can you do? I think the reason that TRD has come into our vocabulary so much more in recent years is that there's more we can do about it. So, it's worth talking about more because we have other things we can do. I'm going to list some of those other things we can do for treatment resistant depression. It's not an exhaustive list by any means, but here's some of the things we can do. One thing we can do for TRD is Transcranial Magnetic Stimulation (TMS). [It is] very safe, very effective. Also, there is Electroconvulsive therapy (ECT). ECT has its advantages and disadvantages. It is certainly has still has a place in psychiatry and it's been around a long time. There's ECT also. And then there's ketamine and esketamine. That's been increasingly used and for good reason. Here I just show the molecules; there's two mirror image molecules. The ketamine is a mixture of those two, esketamine is the one on the left. We have ketamine and esketamine are also good options. There's a lot more things to do. I mean, there's these and then there's, "but wait, there's more." There are psychedelic agents, there's deep brain stimulation, vagal nerve stimulation, direct transcranial current magnetic seizure therapy, [and] probably other stuff too that I don't I didn't remember to put on the slide. There are other options, but the ones I list I think are the main ones. If you can remember one thing from what I'm talking about, it's this: if you have patients who have an inadequate response to what you're doing; you can be doing a great job and your patient can still be doing lousy. If you're in that situation, then what I recommend is this: let's do something different because we've got different stuff. We have other treatments that work very, very well. So as a health care provider, it's our duty to learn as much as we can about these other options so that we can do the very best we can for the patients who trust us with their care.

Transcript was AI-generated and edited for clarity.

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Steve Harvey, MD, discusses the challenges of defining treatment resistant depression and provides and overview of treatment options.

Steve Harvey, MD

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