On September 28, 2023, the FDA approved gepirone extended-release (ER) tablets (Exxua; Fabre-Kramer Pharmaceuticals) for the treatment of adults with major depressive disorder (MDD). Gepirone is a first-in-class antidepressant that selectively targets serotonin 1A receptors. Serotonin 1A is a key regulator of mood and emotion.
“Exxua is the first truly selective agonist of the serotonin 1a receptor that has been consistently linked to mediation of mood disorders and suicide risk. It’s an important addition to the armamentarium to treat depression,” stated Stephen Stahl, MD, PhD, Professor of Psychiatry, University of California, and founder of the Neuroscience Education Institute, in a press release.
The approval of gepirone was based on the results of 2 randomized, double-blind, 8-week, placebo-controlled, flexible-dose studies that included 456 adults aged 18 to 69 years who met the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria for MDD. Of these patients, 226 received gepirone 18.2 mg to 72.6 mg and 230 received placebo.
In study 1, adults with MDD initially received 18.2 mg of gepirone once daily, which was then titrated to 36.3 mg once daily on day 4 of treatment. The dose of gepirone could be increased to 54.5 mg once daily after day 7, and to 72.6 mg once daily after an additional 7 days. In study 2, adults with MDD initially received 18.2 mg of gepirone daily followed by an increase to 36.3 mg daily on days 4 to 7 of treatment. In both trials, the primary efficacy measure was change from baseline in the Hamilton Rating Scale for Depression total score at week 8; the patients in the gepirone treatment groups had significantly greater improvement on this primary end point than patients who received placebo in both studies.
The most frequent (≥5%, at least twice the incidence of placebo) adverse events in the clinical trials of gepirone were dizziness, nausea, insomnia, abdominal pain, and dyspepsia.
“I am thrilled for our patients that Exxua (gepirone ER) is now FDA approved for the treatment of major depressive disorder…. Exxua is the first 5-HT1a agonist with superior efficacy vs. placebo as MDD monotherapy, yet did not differ from placebo in rates of sexual dysfunction in clinical trials. This provides an important new treatment option for patients,” said Anita H. Clayton, MD, Chair of the Department of Psychiatry & Neurobehavioral Sciences, University of Virginia School of Medicine, in a press release.
The recommended starting dose for gepirone is 18.2 mg administered orally once daily with food at approximately the same time each day. Based on clinical response and tolerability, the dose of gepirone can be increased to 36.3 mg once daily on day 4, which may be further titrated to 54.5 mg once daily after day 7 and to 72.6 mg once daily after an additional week.