Ketamine and esketamine for the prevention of postpartum depression: A systematic review and network meta-analysis, with an integrated evidence synthesis.

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.

Study at a glance

Abstract

Postpartum Depression (PPD) is a common condition with serious consequences for both mother and baby if left untreated. Currently, few effective strategies exist for prevention of PPD. Ketamine and Esketamine are rapid acting and potent antidepressants, and emerging evidence is showing promising results for PPD. This review searched the MEDLINE, CINAHL, PsycINFO, EMBASE, and Cochrane databases, including peer-reviewed randomized controlled trials (RCT), pilot studies, and observational studies. The articles studied the effects of ketamine or esketamine interventions on PPD prevention, when administered during pregnancy or postpartum for both c-section and vaginal deliveries. A network meta-analysis (for RCTs) and narrative synthesis (for other study designs) approach was used to analyze the effects of these treatments. Qualitative analysis employed the Cochrane risk of bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Thirty-six studies were identified, five included vaginal delivery, thirty included c-section, and one study did not specify delivery mode. The results of the network meta-analysis and the narrative synthesis suggested that ketamine and esketamine treatment were well tolerated, and may be associated with a reduced risk of developing PPD. However, it is worth highlighting that the quality of the data was low to very low, as such these results should be interpreted with caution. This review suggested that ketamine and esketamine treatment may lower PPD risk. Nevertheless, the poor quality and scarcity of the data, and the limitations presented by current psychiatric practice guidelines, highlight the need for more high-quality, adequately powered studies.