Postpartum depression (PPD) is common and harmful if untreated, with few effective prevention strategies. Ketamine and esketamine are rapid-acting antidepressants showing promise for PPD. This review searched five databases for peer-reviewed randomized controlled trials, pilot studies, and observational studies examining ketamine or esketamine for PPD prevention during pregnancy or postpartum, for both cesarean and vaginal deliveries. A network meta-analysis and narrative synthesis were used. Thirty-six studies were identified; five included vaginal delivery, thirty included cesarean section, and one did not specify delivery mode. Results suggested that ketamine and esketamine were well tolerated and may reduce PPD risk. However, data quality was low to very low, so results should be interpreted cautiously. More high-quality studies are needed.
In a small group of 11 patients with treatment-resistant depression who initially responded to an acute course of ketamine infusions, ongoing maintenance infusions helped sustain the antidepressant effect for some. All patients had lower depression scores during maintenance treatment than at baseline. At the end of the observation period, 4 patients continued maintenance ketamine, 1 switched to intranasal ketamine, 4 stopped because the drug lost its effect, 1 stopped due to side effects, and for 2 the reason was unrecorded. No major adverse events occurred, and the treatment was generally well tolerated. The authors suggest maintenance ketamine may help some responders, but more research is needed on optimal duration and long-term safety.