Evidence lacking for new neurosteroid drugs in treating postnatal depression

Antidepressants are widely used as a drug based intervention to treat more severe cases of postnatal depression. While they are regularly prescribed, they can provide a limited response. The drugs modulate the gamma-aminobutyric acid (GABA) system—which has a key role in regulating brain activity—and have been proposed as an effective alternative to antidepressants.

A paper published in the journal Cochrane Database of Systematic Reviews and led by researchers from King’s College London identified six U.S.-based randomized controlled trials that examined the use of two neurosteroid GABAA positive allosteric modulators—Zuranolone, Brexanolone, and Ganaxolone—for the treatment of postnatal depression in 674 women.

Four of these studies compared either Brexanolone or Ganaxolone delivered intravenously with a placebo control, but the review found that they may make little or no difference to postnatal depression symptoms compared to placebo.

Researchers also identified two studies examining the use of Zuranolone delivered orally versus placebo control. In these studies, the researchers found that it probably reduces postnatal depression symptoms over a 45-day period but with an increase in adverse events such as drowsiness.

While the authors recognize that Zuranolone has promise as a potential intervention for postnatal depression, they conclude that it is too early to make recommendations about its use in clinical practice, as no studies have compared it to other active treatments. The researchers also highlighted that so far there haven’t been any studies on its safety for breastfeeding women.

Dr. Claire Wilson, a researcher at King’s IoPPN, a psychiatrist South London and Maudsley NHS Foundation Trust, and the review’s first author said, “Neurosteroid GABAA positive allosteric modulators have been developed in the hope that they offer a more effective alternative to the antidepressants currently available, but none of the trials have compared the effectiveness of these drugs to widely used, recommended antidepressants. Furthermore, the studies we did analyze only examined the effects over a relatively short period, and were unable to draw conclusions on their safety in breastfeeding.”

So far, these drugs have not been approved outside the U.S. The reviewers suggest that more research is needed on the effectiveness of these agents in other settings, with a range of comparators that are well-established in guidance and clinical practice, and with longer-term follow-up.

Dr. Hind Khalifeh, perinatal psychiatrist at South London and Maudsley NHS Foundation Trust and the review’s senior author said, “For women with postnatal depression, early and effective treatment is necessary. Neurosteroid GABAA positive allosteric modulators have been developed to specifically target depression in the postnatal period, and to offer more rapid treatment. It is encouraging that one of these agents, Zuranolone, is better than placebo. We await trials comparing it to traditional antidepressants to understand its place in clinical practice.”