Tuesday, May 9, 2023

Zuranolone Found to Quickly Reduce Major Depression Symptoms in Phase 3 Trial

Adults with major depressive disorder may experience mood improvements within days of taking zuranolone (50 mg/day), a study in The American Journal of Psychiatry (AJP) suggests. Zuranolone is an oral, once-daily neuroactive steroid that acts on GABA-A receptors.

“[P]atients receiving zuranolone 50 mg/day demonstrated significantly greater improvements in depressive symptoms at day 15 compared with those receiving placebo,” wrote Anita H. Clayton, M.D., of the University of Virginia School of Medicine and colleagues. The study “supports the potential role for a 14-day therapy with oral zuranolone 50 mg/day in adults with MDD [major depressive disorder], with rapid improvements in depressive symptoms observed at the day 3 visit that were sustained through day 42, relatively high response and remission rates, and a favorable safety profile.”

The study was funded by Biogen Inc. and Sage Therapeutics Inc., who are working together on the development of zuranolone.

The phase 3 trial included patients who were between the ages of 18 and 64 years, had received a diagnosis of major depressive disorder (according to DSM-5 criteria), had been experiencing symptoms of depression for a least four weeks, and had a Hamilton Depression Rating Scale (HAM-D) score of at least 24 at screening and before they started taking the assigned study medication.

The researchers randomized the participants to take either 14 days of treatment with zuranolone 50 mg/day or placebo in the evening. Regardless of the participants’ assigned group at the start of the trial, they were permitted to take other antidepressants, provided they had been on a stable dose for at least 60 days before the study began and they agreed to continue taking the medication throughout the study period. The researchers evaluated the participants 10 times over the course of the 42-day trial using such assessments as the HAM-D, the Columbia–Suicide Severity Rating Scale, the Clinical Global Impressions severity score, and more.

A total of 534 patients (266 in the zuranolone group; 268 in the placebo group) were included in the final analysis. The patients in both groups (who were predominantly White and female) had experienced major depressive disorder for a mean of approximately 11 years.

Compared with patients who took placebo, those who took zuranolone demonstrated a statistically significant improvement in depressive symptoms at day 15. “Numerically greater improvements in depressive symptoms for zuranolone versus placebo were observed by day 3 (least squares mean change from baseline HAM-D score, −9.8 vs. −6.8), which were sustained at all visits throughout the treatment and follow-up periods of the study,” Clayton and colleagues wrote.

More than 60% of the patients who took zuranolone reported treatment-emergent adverse events compared with nearly 45% of the patients who took placebo. The most common adverse events (>5% frequency in any group) were somnolence (drowsiness), dizziness, headache, sedation, and diarrhea. Nine patients in the zuranolone group and four in the placebo group discontinued treatment due to treatment-emergent adverse events.

“[E]fficacy and safety results with zuranolone were similar regardless of whether patients were receiving a concomitant antidepressant therapy, suggesting that combination therapy may be a viable option for patients who are currently on an antidepressant therapy but would benefit from a therapy that may improve depressive symptoms with 2 days of treatment,” Clayton and colleagues wrote. “Overall, the study adds to the evidence suggesting that zuranolone constitutes a promising novel therapy for the treatment of MDD in adults.”

For related information, see the Psychiatric News Med Check summary “FDA Grants Zuranolone Priority Review for Major Depression and Postpartum Depression.”

(Image: iStock/gerenme)

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