The efficacy and safety of some new GABAkines for treatment of depression: A systematic review and meta-analysis from randomized controlled trials

Positive allosteric modulators of γ-aminobutyric acid-A (GABAA) receptors, or GABAkines, play important roles in the treatment of depression, epilepsy, insomnia, and other disorders. Recently, some new GABAkines (zuranolone and brexanolone) have been administrated to patients with major depressive disorder (MDD) or postpartum depression (PPD) in randomized controlled trials (RCTs). This study aims to systematically review and examine the efficacy and safety of zuranolone or brexanolone for treatment of depression. A systematic literature retrieval was conducted through August 20, 2023. RCTs evaluating the efficacy and safety of zuranolone or brexanolone for treatment of depression were included. Eight studies (nine reports) were identified in the study. The percentages of patients with PPD achieving Hamilton Depression Rating Scale (HAM-D) response and remission were significantly higher after brexanolone or zuranolone administration compared with placebo at different points. The percentages of patients with MDD achieving HAM-D response and remission were significantly increased during the zuranolone treatment period compared with placebo. In addition, zuranolone caused more adverse events in patients with MDD compared with placebo. Our findings support the effects of brexanolone on improving the core symptoms of depression in patients with PPD, and the potential of zuranolone in treating patients with MDD or PPD.