Two New MDD Approvals: 5-HT1A Agonism and Adjunctive Atypical Antipsychotics

"Two New MDD Approvals: 5-HT1A Agonism and Adjunctive Atypical Antipsychotics" takes up two agents that arrived by very different roads.

Dr. Alva asks Dr. Clayton about two long-awaited approvals with very different stories, noting that gepirone's road to approval spanned decades of complete response letters. He asks where a 5-HT1A agonist with a favorable sexual side effect profile fits, and how she reads lumateperone's data in a crowded field.

Dr. Clayton starts with gepirone ER and addresses the EKG concern directly. That labeling issue traces to the immediate-release formulation. With the extended-release formulation, she says the benefits are substantial and cardiac monitoring is not a significant factor. It also does not cause sexual dysfunction, and she explains why that took so long to establish. Many of the development-era studies used sexual functioning measures likely to provoke a placebo response. Two positive trials were needed and delivered, one against placebo and one against placebo and an SSRI, and the agent beat both. Sexual dysfunction was better than placebo. It is dosed once daily, though the dose must be titrated upward over time. She draws the comparison to buspirone, which clinicians know as well tolerated, while noting gepirone is quite different. She then makes patient preference central. If someone says they do not want sexual dysfunction and has already tried bupropion, she says gepirone ER deserves consideration.

On lumateperone, Dr. Clayton notes it is an atypical antipsychotic with several mechanisms, already approved in bipolar depression and now for adjunctive treatment in major depressive disorder. Dosing is simple, since the starting dose of 42 mg once daily can be the final dose, with 21 mg available. She cites a six-month study in which 80% were responders and 65% were remitters, with scores continuing to fall over time.

Up next, in "Defining Response, Remission, and Residual Symptoms in MDD," Dr. DeBattista explains why he never uses the words response or remission with a patient.