EMA OKs Oral Treatment for Postnatal Depression

The Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) has adopted a positive opinion on zuranolone (Zurzuvae, Biogen Netherlands BV), the first oral drug to treat postpartum depression in adults. Marketing authorization was granted in recognition of clinical trial results showing a reduction in postpartum depressive symptoms after 2 weeks’ treatment.

Zuranolone is a neuroactive steroid that enhances the activity of the neurotransmitter gamma-aminobutyric acid (GABA). It is thought to exert antidepressant effects by enhancing GABAergic inhibition.

In a multicenter, randomized, double-blind, placebo-controlled study, zuranolone at a 50 mg dose was given for 14 days to women who met the Diagnostic and Statistical Manual of Mental Disorders criteria for a major depressive episode of postpartum depression and whose symptoms started in the third trimester or within 4 weeks of delivery. Compared with placebo, the active group demonstrated significantly greater symptom improvement on days 3,15 (the primary endpoint), and 45, using the standard 17-item Hamilton rating scale for depression.

The FDA approved the drug in August 2023, at which time it was the first oral treatment for postpartum depression, with previous therapies requiring intravenous dosing. 

It is available in 20 mg, 25 mg, and 30 mg capsules. The most common side effects are somnolence, dizziness, confusion, trouble walking, and sedation. Patients are advised to avoid alcohol and not to drive, operate machinery, or undertake other dangerous activities until at least 12 hours after taking each dose during the 14-day treatment course.

There may also be an increased risk of suicidal thoughts and actions in people 24 years of age and younger. Animal studies have suggested a possible risk of teratogenic effects, so women who may become pregnant are advised to use effective contraception during treatment and for 1 week after the final dose, and to alert their healthcare provider should they become pregnant during treatment.

The EMA said that detailed recommendations will be described in the summary of product characteristics, which will be published on the EMA website in all official European Union languages after the marketing authorization has been granted by the European Commission.

Perinatal Mental Healthcare ‘in Its Infancy’

In Western countries, postpartum depression is estimated to affect between 10% and 15% of women during the first year after birth , with substantial differences in rates depending on socioeconomic factors such as marital status, educational level, social support, spouse care, violence, gestational age, breast feeding, child mortality, financial difficulties, partnership, life stress, smoking, alcohol intake, and living conditions.

Common symptoms include feelings of desperation, sadness, anxiety, irritability, and isolation, as well as nausea, changes in sleep and eating habits, decreased libido, crying spells, mental lability, thoughts of hurting oneself and/or the infant, and suicidal ideation. 

The condition can wreak havoc on women’s mental health as well as that of their partners. It can impair the parental relationship, the mother-child bond, and the emotional and cognitive growth of infants, with potential long-term effects. Postnatal depression may occur alongside post-traumatic stress disorder following stressful or traumatic childbirth experiences .

Yet a review published in Frontiers in Psychiatry last year suggested that fewer than half of countries in the World Health Organization (WHO) European region had policies specifically on perinatal mental health, leading its authors to conclude that “perinatal mental health care is in its infancy in most WHO European countries.”

Dr Sheena Meredith is an established medical writer, editor, and consultant in healthcare communications, with extensive experience writing for medical professionals and the general public. She is qualified in medicine and in law and medical ethics.