US approves pill to treat postpartum depression

The Food and Drug Administration (FDA) in the United States has approved a new medication to treat postpartum depression (PPD).

Zuranolone, which is made by Sage Therapeutics and Biogen and sold under the brand name Zurzuvae, is a pill taken once a day for two weeks. Previously, treatment for PPD was available only as an intravenous injection. It is expected to be made available later this year.

In clinical trials, Zuranolone helped to significantly reduce depressive symptoms within three days. The effect of the medication was still present at four weeks after the last dose, the FDA said. It added that the most common side-effects from taking Zurzuvae include drowsiness, dizziness, diarrhoea, fatigue, the common cold and urinary tract infection. It may also, however, cause suicidal thoughts and behaviour, as well as harm to a fetus, the FDA warned.

The FDA said that labelling includes a warning that Zurzuvae can affect a person’s ability to drive and perform other potentially hazardous activities. It recommends patients should not drive or operate heavy machinery for at least 12 hours after taking it.

In the past, treatment options for postpartum depression have included counselling or therapy with a mental health professional and antidepressant medication, but until Zulresso (a drug taken intravenously) and zuranolone, no antidepressant medication had been specifically FDA-approved to treat PPD.

Zuranolone is a synthetic version of a naturally occurring substance in the body called allopregnanolone. Levels of allopregnanolone can rise dramatically during pregnancy and then abruptly drop after childbirth, potentially contributing to postpartum depression.

Two successful RCTs

Tiffany Farchione, director of the division of psychiatry in the FDA’s Center for Drug Evaluation and Research, described PPD as 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.” She added: “And, because postpartum depression can disrupt the maternal-infant bond, it can also have consequences for the child’s physical and emotional development. Having access to an oral medication will be a beneficial option for many of these women coping with extreme, and sometimes life-threatening, feelings.”

The efficacy of Zurzuvae for the treatment of PPD in adults was demonstrated in two randomised, double-blind, placebo-controlled, multi-centre studies. The trial participants were women with PPD who met the Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for a major depressive episode and whose symptoms began in the third trimester of pregnancy, or within four weeks of delivery.

In the first study, patients received 50mg of Zurzuvae or placebo once daily in the evening for 14 days. In the second, patients received another zuranolone product that was approximately equal to 40mg of Zurzuvae or placebo, also for 14 days. Patients in both studies were monitored for at least four weeks after the 14-day treatment. On day 15, depressive symptoms were measured using the Hamilton depression rating scale (HAMD-17). Patients in the Zurzuvae groups showed significantly more improvement in their symptoms than those in the placebo groups. The treatment effect was maintained at Day 42 – four weeks after the last dose of Zurzuvae.

Sage Therapeutics and Biogen had also sought approval to use zuranolone for major depressive disorder (MDD), or clinical depression. The FDA refused this, however, saying that the medication did not provide substantial evidence of effectiveness and that an additional study or studies would be needed. Sage Therapeutic said it was “highly disappointed for patients, particularly amid the current mental health crisis and millions of people with MDD struggling to find symptom relief.”