Zuranolone Effectively and Safely Treats Postpartum Depression

A study published in the American Journal of Psychiatry on July 26, 2023, proved that zuranolone could effectively and safely treat postpartum depression. The study supports the priority review granted by the FDA to the manufacturers: Biogen Inc. and Sage Therapeutics.

In February 2023, the FDA accepted the companies’ New Drug Application (NDD) for the drug and granted priority review simultaneously, with indications for major depressive disorder (MDD) and postpartum depression (PPD). As the Prescription Drug User Fee Act (PDUFA) action date of August 5, 2023, approaches, the study results may support the drug’s full approval for PPD.

Postpartum depression is a common complication during pregnancy and postpartum. An article published in Current Psychiatry Reports revealed that PPD accounts for 20% of postpartum deaths. While many pregnant and postpartum individuals experience baby blues — characterized by mood swings, anxiety, sadness, difficulty concentrating, appetite changes, and sleep complications — the condition can worsen and become PPD.

Unlike the baby blues, PPD lasts over two weeks and has more intense symptoms, including difficulty bonding with the baby, extreme irritability, shame, feelings of inadequacy, severe anxiety, panic attacks, self-harm, thoughts of harming the baby, and suicidal thoughts. While researchers need more data before identifying the causes of PPD, a family history of psychiatric disorders or PPD, genetics, stressful events, or a personal history of depression may increase the risk of PPD.

Despite PPD definitions restricting the condition to one year after childbirth, a Pediatrics article notes that 25% of PPD patients experienced depressive symptoms after three years.

Considering the condition's severe side effects and longevity, exploring new treatments beyond the current options is critical. Zuranolone’s efficacy and safety results are promising for PPD treatment.

Zuranolone (SAGE-217/BIIB125) is a neuroactive steroid (NAS) GABA-A receptor positive allosteric modulator (PAM) that is given as an oral pill once daily for two weeks. The double-blind phase 3 clinical trial recruited 196 patients with severe PPD, randomizing patients to take zuranolone or a placebo at a 1:1 ratio.

Only 170 patients completed the study; however, zuranolone significantly improved depressive symptoms by day 15. More specifically, on day 15, the Hamilton Depression Rating Scale (HAM-D) score decreased by 15.6 points, while the placebo group only experienced an 11.6-point decline.

Additionally, the researchers noted that the most common side effects were somnolence, dizziness, and sedation.

The researchers concluded, “zuranolone demonstrated significant improvements in depressive symptoms and was generally well tolerated, supporting the potential of zuranolone as a novel, rapid-acting oral treatment for PPD.”