This article presents two novel treatments for postpartum depression – brexanolone and zuranolone – and evaluates their efficacy and safety based on randomised clinical trials. Postpartum depression is a common mental health disorder affecting women after childbirth. Studies indicate that it may affect up to 25% of mothers in the postnatal period. Brexanolone and zuranolone are novel medications that act as modulators of GABA‑A receptors, offering the potential for faster and more effective treatment. Randomised clinical trials and subsequent meta‑analyses have demonstrated that intravenously administered brexanolone produces a significant reduction in symptoms within 24 hours, with effects lasting for at least 30 days. By contrast, orally administered zuranolone achieved symptom remission in 45% of patients after 15 days of therapy, with benefits persisting for at least 45 days. Brexanolone and zuranolone represent promising therapeutic options for women experiencing postpartum depression, offering both rapid and sustained relief of symptoms. These agents mark a significant advance in the pharmacological management of postpartum depression, addressing the critical need for faster onset of action compared with traditional antidepressants, which often require several weeks to exert an effect. Both drugs are generally well tolerated, although side effects such as drowsiness, headache, and dizziness may occur. Further studies are warranted to fully evaluate the long‑term safety and efficacy of these novel treatments.