Brexanolone, zuranolone and related neurosteroid GABA

backgroundPostnatal depression - depression that occurs up to one year after a woman has given birth - is an important and common disorder that can have short- and long-term adverse impacts on the mother, her child and the family as a whole. Recommended treatment for postnatal depression is psychological therapy, and for more severe depression, antidepressants. However, many antidepressants are associated with limited response. Neurosteroid gamma-aminobutyric acid (GABA

objectivesTo assess the benefits and harms of brexanolone, zuranolone and related neurosteroid GABA SEARCH

methodsWe searched Cochrane Common Mental Disorders' Specialised Register, CENTRAL, MEDLINE, Embase and PsycINFO in January 2024. We also searched two international trials registries and contacted experts in the field to identify the studies that are included in the review. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of women with depression during the first 12 months following childbirth that compared neurosteroid GABA DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. The primary outcomes were depression response, depression remission and adverse events experienced by the mother, nursing baby, or both. The secondary outcomes were depression severity, treatment acceptability, quality of life and parenting- and child-related outcomes. We grouped analyses according to whether the neurosteroid GABA MAIN

resultsWe identified six RCTs (674 women); all were placebo-controlled trials. Three studies tested intravenous brexanolone; one, intravenous ganaxolone; and two studies, oral zuranolone. Sample sizes ranged from 21 to 196. All were conducted in the USA. We judged the risks of selection, performance, detection, attrition and reporting biases to mostly be low, although the risk of selection and attrition bias was unclear in two studies. The biopharmaceutical companies which made the drugs sponsored all six included studies. They appear to have had a considerable role in the design and conduct of the studies. Intravenous neurosteroid GABA AUTHORS'

conclusionsThis review provides moderate-certainty evidence that zuranolone probably improves depression response and remission but also increases maternal adverse events compared to placebo. There may be little or no difference in depression response and remission and probably little or no difference in maternal adverse events with intravenous neurosteroid GABA