Evaluating Response to TRD Treatment


Ms Maroney drives a conversation regarding response to treatment-resistant depression.

Megan Maroney, PharmD, BCPP: Dr Skolnik, how do you define a partial response vs a complete response? How does a partial response change the course of treatment?

Neil Skolnik, MD: That’s a good question. A partial response is not feeling back to normal but [feeling] better. I believe the literature says 50% improvement in a rating scale, which is substantial but not back to normal. No response is very little change. There can be a little movement because there’s variability from time to time. But very little movement in terms of either the rating scale or how they’re feeling. Both are related but separate ways to gauge response.

Megan Maroney, PharmD, BCPP: Dr Thase, you already mentioned dual therapy in terms of adding an atypical antipsychotic, but when would you switch antidepressant therapies vs adding a treatment?

Michael Edward Thase, MD: Rule No. 1 is if you have a deal-breaking adverse effect with that index antidepressant, it’s out the door. At an early stage of treatment, you don’t want to try antidotes to cover adverse effects when you can simply move to a dissimilar antidepressant. I’ll switch antidepressants for that reason. I’ll also switch antidepressants if I’ve learned something in that initial trial that points me in the direction of a better alternative antidepressant. For example, if a patient has their appetite suppressed and can’t sleep on an SSRI [selective serotonin reuptake inhibitor] or an SSNRI [selective serotonin and norepinephrine reuptake inhibitor], I might go to mirtazapine as a second-line antidepressant. I favor milder adjuncts when the patient is better but not well and they’re not moving from better to well by continuing on the treatment.

Then I’ll look for a medicine that might have an additive or complementary effect on a symptom or 2 or 3 that is persisting for the patient. Here’s an example where judicious use of a benzodiazepine may still be valuable for a patient who’s not at significant risk for substance use or abuse. But for a patient who is tired and has low motivation, bupropion can be the additive second medication for that patient. I’ll switch quickly for a patient who has both adverse effects and no benefit. If that’s clear at 4 weeks, with no benefit and deal-breaking adverse effect, they’re off that medicine. It failed. I’ll move to something dissimilar next.

Megan Maroney, PharmD, BCPP: Even if they were to start working, if they’re having this horrible adverse effect, chances are they’re going to stop taking it either way, right?

Michael Edward Thase, MD: Yes.

Megan Maroney, PharmD, BCPP: Mr Cannon, how do partial responses impact the treatment sequence from a payer’s perspective? [I’m talking about] prior authorization and step edits for add-on treatments.

Eric Cannon, PharmD, FAMCP: We’ve tried to say that don’t want to create barriers. If you go back to some of the treatments that Dr Thase and Neil were working through, we don’t put barriers in place. Something we harp on with our teams is that if you get a call from a pharmacy, make sure those claims are going through. We don’t want to stop them. We do have prior authorization, for example, on esketamine. The flip side is we don’t have prior authorization on the infusional ketamine. In trying to put all those options out there, we’ve said, “Here’s what we think.”In fact, right now, we don’t require prior authorization on any of the antidepressants. We have some step therapy on some of the newer products that require trial and failure of something less expensive. What we’ve found is that most clinicians are practicing in a stepwise fashion anyway so, we’ve created a relationship where we don’t want to hold patients back. We want them to have access to treatment.

Megan Maroney, PharmD, BCPP: Does that differ in terms of dual therapy? Does partial response qualify patients for additional dual therapies earlier?

Eric Cannon, PharmD, FAMCP: No. In terms of dual therapy, you try to put somebody on 2 atypical [drugs]. We will stop that. You try to put somebody on an antidepressant or an atypical, or you augment with something else. We’ve set things up so dual therapy is allowed to go through. At 1 point in time, we had edits around SSRIs and some of the other treatments that have since been removed. It costs more to answer the phone call when the claim doesn’t go through than it does to pay for the prescription in a lot of instances. Let’s get drugs to patients who need them.

Megan Maroney, PharmD, BCPP: Allow for rational polypharmacy, right?

Eric Cannon, PharmD, FAMCP: Absolutely.

Megan Maroney, PharmD, BCPP: Dr Skolnik, how about you? You touched on this before, but do you use adjunctive atypical antipsychotics? At what point do you use those?

Neil Skolnik, MD: Usually I don’t, to be honest, for exactly the reasons that Dr Thase talked about. That’s when I’ll refer them to a psychiatrist. I’ll usually start with an SSRI or an SNRI, sometimes bupropion. My add-on is usually bupropion, sometimes mirtazapine. Because of the adverse effects of antipsychotics—I’m not saying it’s wrong; many primary care doctors are comfortable using them—I’ll usually send that patient. The decision is then about using a second-generation antipsychotic. Another medicine that we haven’t talked about that’s sometimes used is lamotrigine. Which way to go is something I’ll [send to a psychiatrist]. Michael, I’m glad you mentioned the term “degree of misery.” As I reflect on that, I think about the question you asked when I send a patient on. That strongly influences it as well. If a patient has severe depression, I’m going to be a lot quicker to send that patient to an expert, who can make decisions about how we help that patient as quickly as possible. That’s a good point. I want to emphasize that.

Michael Edward Thase, MD: Depression is such a low-energy state, and patients are so demoralized and pessimistic to begin with. If you just have any slippage in your care system and they can fall through the cracks, it seems like a predestined event. Of course, out of your care, they miss the nonspecific benefits, and they miss the opportunity for you to manage their treatment in the most decisive and effective way.

Megan Maroney, PharmD, BCPP: Dr Thase, how do you determine when a patient is experiencing a partial response? The same as what Dr Skolnik had talked about?

Michael Edward Thase, MD: I think of the depression severity continuum in quartiles. If a patient has moved less than 1 quarter toward better, I call that a nonresponse. If a patient has moved almost to the halfway point of being better, I’m on the right track, but what can I do to refine that? That’s what I call a partial response. They’re better but not over the line. If they’re more than 50% better but not back at their well self, I’ll call that a response. If they’re back at their well-self, we’ll call that a remission.

Transcript edited for clarity.

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