Patients taking Zuranolone for major depression symptoms showed quick mood improvements: Phase 3 trial

The study showed that zuranolone at 50 mg/day led to mood improvements in patients within days of treatment and was well-tolerated with no new safety findings compared with previously studied lower dosages. Zuranolone is a once-daily, oral neuroactive steroid that acts on GABA-A (γ-aminobutyric acid type A) receptors.

"Zuranolone at 50 mg/day elicited a remarkably greater improvement in depressive symptoms at day 15, with a rapid time to effect (day 3)," the researchers wrote in their study.

Anita H. Clayton from the University of Virginia School of Medicine and colleagues aimed to evaluate the safety and efficacy of a 14-day treatment course of once-daily zuranolone 50 mg, an investigational oral positive allosteric modulator of the GABAA receptor, for the treatment of major depressive disorder in a double-blind, randomized, placebo-controlled trial.

The study enrolled patients 18–64 with severe major depressive disorder. Patients were self-administered once daily zuranolone 50 mg or placebo for 14 days. A change in total score on the 17-item HAM-D (Hamilton Depression Rating Scale) on day 17 was noted. The incidence of adverse events was used to assess safety and tolerability.

534 (268 in the placebo group, 266 in the zuranolone group) constituted the complete analysis set of 543 randomized patients.

The study led to the following findings:

· Compared with patients in the placebo group, the zuranolone group demonstrated a statistically significant improvement in depressive symptoms at day 15 (least squares mean change from baseline HAM-D score, −14.1 versus −12.3).

· Numerically more significant improvements in depressive symptoms were observed for zuranolone versus placebo by day 3 (least squares mean change from baseline HAM-D score, −9.8 versus −6.8), which were sustained at all visits throughout the treatment and follow-up study periods (through day 42, with the difference remaining nominally significant through day 12).

· Two patients in each group experienced a severe adverse event; four in the placebo group and nine patients in the zuranolone group discontinued treatment due to adverse events.

"The findings showed that Zuranolone was generally well tolerated, with no new safety findings versus previously studied lower dosages," the researchers wrote. "These findings support zuranolone's potential in treating adults with major depressive disorder."

Reference:

The study, "Zuranolone for the Treatment of Adults With Major Depressive Disorder: A Randomized, Placebo‐Controlled Phase 3 Trial," was published in The American Journal of Psychiatry.

DOI: https://doi.org/10.1176/appi.ajp.20220459