Novel pill shows promise in treating postpartum depression

A novel investigational postpartum depression pill has shown significant improvement in depressive symptoms in Phase 3 clinical trial.

The Feinstein Institutes for Medical Research at Northwell Health have announced the results from the SKYLARK Study, a phase 3 placebo-controlled clinical trial of an investigational oral, neuroactive steroid zuranolone pill in the treatment of postpartum depression, demonstrating the drug showed rapid, clinically meaningful improvements in depressive symptoms at measured time points.

This would support the potential for the US Food and Drug Administration (FDA) approval of the first oral, at-home, neuroactive steroid therapy to treat PPD.

Approximately one in eight women experience perinatal or postpartum depression (PPD) and current treatment options such as therapy can take months for new mothers to find symptom relief.

The trial, led by Dr Kristina M. Deligiannidis – professor at the Institute of Behavioral Science at the Feinstein Institutes – and published in The American Journal of Psychiatry, has shown a 14-day treatment with zuranolone versus placebo resulted in “significant” improvement in depressive symptoms.

At day 15, the study’s primary outcome measure, with statistically significant improvement in depressive symptoms, reported as early as day three and with improvements sustained at all measured time points through day 45.

Results showed that 57 per cent of the women taking zuranolone versus 38 per cent of women taking placebo experienced a 50 per cent or more improvement in their depressive symptoms at day 15.

At day 45, 61 per cent of the trial participants who received zuranolone compared to 54 per cent of women receiving placebo, experienced a 50 per cent or more improvement in their depressive symptoms.

“Postpartum depression is underrecognised, undertreated and disruptive for those who live with the condition, said” Dr. Deligiannidis, the trial’s principal investigator and lead author of the paper.

“We collaborate with researchers around the world in an effort to develop more rapid and effective therapies for the many women who need support.

“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.”

Among the 200 enrolled patients and randomised diverse patients screened across international clinical sites, 196 female patients between ages 18 to 45 with postpartum major depressive episodes received the blinded study drug.

Zuranolone (50mg) or placebo was given once daily for 14 days and the patient’s depressive symptoms were evaluated at several defined points in the study for 45 days.

In 2021, Dr Deligiannidis reported the publication of the phase 3 results of the ROBIN Study, which was published in the Journal of the American Medical Association (JAMA) Psychiatry.

The trial demonstrated the improvement in depressive symptoms with zuranolone at 30mg versus placebo in patients with PPD and that zuranolone was generally well tolerated.

Evidence suggests that PPD is partly due to a disruption in the normal interaction between the nervous system’s stress response, ɣ-aminobutyric acid (GABA) signalling, and neuroactive steroids (NAS).

The SKYLARK and ROBIN clinical trials, researchers say, could provide some of the most substantial results for improving depressive symptoms in women with PPD.

Dr Kevin Tracey, president and CEO of the Feinstein Institutes, said: “Dr Deligiannidis is a leader in postpartum depression medical research.

“These clinical trial results are evidence that years of perseverance and dedication lead to significant advances in medicine.”