FDA Approves Fast-Acting Postpartum Depression Pill

This story was updated on August 4th to reflect FDA approval.

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Help is here for the 10-20 percent of new moms diagnosed with postpartum depression (PPD).

Zuranolone, an experimental pill that mitigates PPD symptoms, has been approved by the US Food and Drug Administration (FDA) as the first oral medication indicated to treat the mood disorder that affects new mothers, causing feelings of sadness, anxiety, and exhaustion after childbirth.

“Postpartum depression is a serious and potentially life-threatening condition in which women experience sadness, guilt, worthlessness—even, in severe cases, thoughts of harming themselves or their child. And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development,” said Tiffany R. Farchione, M.D., director of the Division of Psychiatry in the FDA’s Center for Drug Evaluation and Research. “Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”

SKYLARK TRIAL RESULTS

Findings from the recent SKYLARK study, published in the American Journal of Psychiatry, support the idea that a 14-day course of zuranolone is safe and effective for treating severe PPD. The study randomly assigned 196 patients to take either zuranolone or a placebo pill. Researchers tracked participant response using a depression rating scale and a global severity score over the two-week period.

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The new mothers treated with zuranolone experienced a significant 35 percent improvement in depressive symptoms compared to the placebo group, measured by the 17-item Hamilton Depression Rating Scale (HAM-D) score at day 15. They also showed meaningful alleviation in depressive symptoms at days 3, 28, and 45 compared to the placebo group. Furthermore, the zuranolone group reported a considerably better Clinical Global Impressions severity (CGI-S) score at day 15 compared to the placebo group.

The trial was led by Kristina M. Deligiannidis, MD, professor at the Institute of Behavioral Science at the Feinstein Institutes.

“Postpartum depression is underrecognized, undertreated, and disruptive for those who live with the condition. We collaborate with researchers around the world in an effort to develop more rapid and effective therapies for the many women who need support,” Deligiannidis said in a media release. “We have been working on neuroactive steroid research in PPD for nearly 15 years. The SKYLARK study follows previous successful clinical trials, and publishing its results is a pinnacle moment in treating postpartum depression.”

The medication’s most common side effects included sleepiness, dizziness, and sedation. Notably, there were no reports of loss of consciousness, withdrawal symptoms, or increased suicidal ideation.

ZURANOLONE’S Mechanism

Zuranolone is a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors and a neuroactive steroid. It functions by enhancing the activity of gamma-aminobutyric acid (GABA), a neurotransmitter that regulates mood and anxiety in the brain. Unlike traditional antidepressants, which can take weeks to start working, zuranolone seems to have a rapid onset of action.

The makers of the drug, Sage Therapeutics and Biogen, have submitted zuranolone for approval to the US Food and Drug Administration (FDA) for the treatment of PPD. The FDA has already granted the drug Breakthrough Therapy designation, aimed at expediting its development and review. This designation was based on the results from last year’s phase 3 ROBIN trial, which demonstrated the drug’s significant benefits for new mothers diagnosed with PPD within days of starting treatment.

Accelerated Approval

The study’s relatively small sample size and a short treatment period mean it’s still not clear how safe and effective zuranolone is over the long term. But the drug’s approval provides a much-needed treatment for a condition that currently has limited options. The only other drug available to treat PPD is zulresso, which is administered through an IV continuously for 60 hours.

“These clinical trial results are evidence that years of perseverance and dedication lead to significant advances in medicine,” Kevin J. Tracey, MD, the president, and CEO of the Feinstein Institutes and Karches Family Distinguished Chair in Medical Research, said in the release.