Megan Maroney, PharmD, BCPP: Welcome to this Drug Topics® Around the practice® exploring the treatment landscape for treatment-resistant depression (TRD). My name is Megan Maroney. I am a clinical associate professor at the Ernest Mario School of Pharmacy at Rutgers University (in Piscataway, New Jersey) and a psychiatric clinical pharmacist at Monmouth Medical Center (in Long Branch, New Jersey). Joining me today in this discussion are Dr. Skolnik, Dr. Thase, and Dr. Cannon.
Neil Skolnik, MD: (My name is) Neil Skolnik. I am a professor of family and community medicine at the Sidney Kimmel Medical College of Thomas Jefferson University (in Philadelphia, Pennsylvania). It is a pleasure to speak on a critically important topic in primary care.
Michael Edward Thase, MD: My name is Michael Thase. I am a professor of psychiatry at the Perelman School of Medicine (at) the University of Pennsylvania (in Philadelphia), and I am also a member of the medical and research staff at the Corporal Michael J Crescenz Veterans Affairs Medical Center in Philadelphia. .
Eric Cannon, PharmD, FAMCP: My name is Eric Cannon, Director of Pharmacy at Select Health, which is the payer for Intermountain Healthcare in Salt Lake City, Utah. I’m delighted to be here today.
Megan Maroney, PharmD, BCPP: Today we’ll talk about several topics related to treatment-resistant depression, including defining what treatment-resistant depression is, exploring the treatment landscape, and discussing the impact of living with treatment-resistant depression or TRD. So let’s talk about how we define TRD. Dr. Skolnik, I’ll start with you. What is TRD and how do we distinguish it from major depressive disorder? Is there a universal definition?
Neil Skolnik, MD: I don’t know if there is a universal definition, because there are different definitions. But the most common is an inadequate response to two or more antidepressants, usually of different classes, given at an adequate dose for an adequate duration. More important than the technical definition is our emphasis in primary care, because that’s where much of (the management of) depression occurs. (We are) aware that many of our patients do not fully respond. So what’s done is we see someone who meets the criteria for major depression. We start them on first-line treatment, often an SSRI (selective serotonin reuptake inhibitor) or SNRI (serotonin norepinephrine reuptake inhibitor), and then we say, “We’ll see you some time later.” ; we will talk about the importance of follow-up. And as long as they’re doing a little better, we’ll continue that approach. An important thing that we all need to be aware of in primary care is how often (patients) do not fully respond, whether it is a partial response (with) depression and (they) warrant intervention additional or (they have) a TRD. .
Megan Maroney, PharmD, BCPP: Would you say that the sequenced treatment alternatives for depression relief in the STAR*D trial (NCT00021528) (affected) the definition of TRD?
Neil Skolnik, MD: (They) have certainly (affected) our knowledge of how to (manage) TRD and given us (an) incredibly well-done, evidence-based study. But some guidelines on what to do have been adopted. So this was a rigorous, well-conducted study with multiple levels of intervention for (patients) who sequentially might not have responded to initial treatment. This has greatly advanced our knowledge.
Megan Maroney, PharmD, BCPP: And even though this was done several years ago, it is still relevant today. Dr. Thase, what are the staging models used to classify the severity of TRD in practice?
Michael Edward Thase, MD: Well, the first one was the one I did with my colleague John Rush, before we started the STAR*D study. This is sometimes called the Thase-Rush (pattern). It’s very simple and straightforward, and we’ve established a hierarchy of first-line, second-line, third-line, and fourth-line treatments. When we first did this model, we suggested that electroconvulsive therapy (ECT) was the last common denominator. So it would be in the fourth line. Since then we have had a few more treatments, and perhaps ECT is no longer the last common denominator but a level 1 or a stage 1. We have had colleagues in oncology who, a few years after having presented this model, said (that) these are levels, not stages; the stages involve the pathophysiology of the disease, the levels involve the description. Our staging model should have been called the leveling model. So, level 1 would be someone who had a good, adequate trial of a first-line level 1 antidepressant, and level 2 would be someone who had a good trial of a second alternative treatment after the first line . There were a few adjunctive treatments when we initially proposed. Adjunctive treatments are more used today than 20 years ago. So you might be at level 2 if the sertraline didn’t work and the addition of aripiprazole didn’t work. This could therefore qualify you to be at treatment resistance level 2. As Neil said, this would be the entry into diagnosing TRD: 2 adequate tries in the current episode. We thought about level 3 involving older generation antidepressants: tricyclic (and monoamine) oxidase inhibitors. They’re probably up to level 4 these days. Esketamine and TMS (transcranial magnetic stimulation) could be considered level 3 treatments that were not approved in 1995 when we first did it. The more vigorous the treatments of a more advanced nature, the more resistant the person is to the treatment. be). So it’s categorical. There are categories, and they are also continuous in the sense that a person who has received 7 strong treatments during the current episode is probably more resistant to the treatment than a person who has received 2. But in the STAR*D study, the first choice treatment achieved approximately 50% of (patients) improved and the second choice treatment improved approximately 40% of (patients). But between the second and the third there was a point of discontinuity; the improvement dropped by almost 20%. This is one of the reasons why (individuals) felt confident saying, “We don’t want to say treatment-resistant until a person has had 2 trials of reasonable first- or second-line treatments . » And this drop between second and third line treatments in STAR*D was indeed impressive. Thus some (individuals) sometimes criticize the 2 tests as not being rigorous enough. I think it’s just rigorous enough to move on to more advanced interventions.
Megan Maroney, PharmD, BCPP: It seems that at this point there is actually differentiation for many patients.
Transcript edited for clarity.
