FDA approves first known pill for postpartum depression

Sage Therapeutics and Biogen have announced that the US Food and Drug Administration (FDA) has officially approved Zurzuvae (zuranolone), understood to be the first and only oral medication indicated to treat adults with postpartum depression (PPD) — a major depressive episode that typically occurs after childbirth but can also begin during the later stages of pregnancy. The daily recommended dose is 50 mg and the treatment should be taken once every day, for 14 days, in the evening with a fatty meal.

As with other forms of depression, PPD is characterised by sadness and/or loss of interest in activities that one used to enjoy and a decreased ability to feel pleasure. It can present with symptoms such as cognitive impairment, feelings of sadness or inadequacy, loss of energy or suicidal ideation. Until now, treatment for PPD was only available as an IV injection given by a healthcare provider in certain healthcare facilities.

The efficacy of Zurzuvae for the treatment of PPD in adults was demonstrated in two randomised, double-blind, placebo-controlled, multicentre studies of women diagnosed with PPD (the ROBIN and SKYLARK Studies). In the SKYLARK Study, patients received 50 mg of Zurzuvae or a placebo once daily in the evening for 14 days. In the ROBIN Study, patients received another zuranolone product that was approximately equal to 40 mg of Zurzuvae or a placebo, also for 14 days. Patients in both studies were monitored for at least four weeks after the treatment.

The primary endpoint of both studies was a change in depressive symptoms using the total score from the 17-item Hamilton depression rating scale (HAMD-17), measured at day 15. Patients in the Zurzuvae groups showed significantly more improvement in their symptoms compared to those in the placebo groups. All key secondary endpoints were met in the SKYLARK Study, with a significant reduction in depressive symptoms seen as early as day 3 and sustained through day 45 — four weeks after the last dose of Zurzuvae.

With the primary endpoint met and Zurzuvae generally well-tolerated by study participants, the FDA granted the application Priority Review and Fast Track designation. Zurzuvae is expected to launch and be commercially available in the fourth quarter of 2023, following scheduling as a controlled substance by the US Drug Enforcement Administration, which is anticipated to occur within 90 days.

The labelling will include a warning that Zurzuvae can impact a person’s ability to perform potentially hazardous activities, so patients should not drive or operate heavy machinery for at least 12 hours after taking the treatment. As with other antidepressant medicines, Zurzuvae may increase the risk of suicidal thoughts and actions. Zurzuvae may also cause foetal harm, so women should use effective contraception during the treatment cycle and for one week afterwards.

The FDA has also responded to a New Drug Application (NDA) for zuranolone to be used in the treatment of adults with major depressive disorder (MDD). In its Complete Response Letter (CRL), the FDA stated that the application did not provide substantial evidence of effectiveness to support the approval of zuranolone for the treatment of MDD and that an additional study or studies will be needed. Sage and Biogen are currently reviewing the feedback and evaluating their next steps.

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