The potential effects and tolerability of analgesic and peri/intra/post-operative esketamine in preventing postpartum depression: An updated systematic review and meta-analysis of randomized controlled trials

Postpartum Depression (PPD) is one of the most common conditions in the childbearing period, with prominent impairments for the mother and the newborn. Esketamine has shown potent antidepressant effects and appears to be a promising agent in preventing PPD. We aimed to evaluate the potential effect of esketamine in preventing PPD within the first week and within four and six weeks post-delivery as the primary outcome; assess changes in the Edinburgh Postnatal Depression Scale (EPDS) one week and 42 days post-delivery; and evaluate tolerability and changes in inflammatory markers as secondary outcomes. A subanalysis was conducted considering different intervention protocols. A systematic review and meta-analysis (ID: CRD42024513598) were performed considering Randomized Clinical Trials (RCTs) in MEDLINE (PubMed), Embase, and Web of Science from inception until May 5, 2024. The ROB-2 tool assessed the risk of bias. Eleven RCTs were included, totaling 2316 participants. The occurrence of PPD was significantly lower in the intervention group within one week post-delivery (RR 0.44, 95% CI 0.30–0.64, p < 0.01; z = −4.25, tau 2 = 0.1531, I 2 = 54%, p = 0.03) and within four/six weeks post-delivery (RR 0.56, 95% CI 0.39–0.76, p < 0.01; z = −3.55, tau 2 = 0.1444, I 2 = 60%, p < 0.01). The presence of dizziness, drowsiness, and nausea was not significantly different between groups. Changes in EPDS score within one week post-delivery were not statistically significant and neither were changes 42 days post-delivery. No significant differences in inflammatory marker levels were found. Our updated meta-analysis suggests that esketamine is an effective agent in preventing PPD within six weeks post-delivery. • Postpartum Depression (PPD) is a mental health condition with high prevalence and significant impairments across several domains for the mother and the newborn. • Antidepressants, mainly Selective serotonin reuptake inhibitors (SSRIs), have not demonstrated effects in preventing PPD. On the other hand, esketamine, in addition to its antidepressant effects, has been showing evidence of the possibility of avoiding the occurrence of PPD. • In this meta-analysis, we updated and summarized the growing evidence of using esketamine as a peri/intra and post-cesarean section and as a labor analgesic agent. • Esketamine showed a significant effect in preventing PPD in the first week and within four-six weeks post-delivery. Moreover, regarding side effects, esketamine appeared to be well tolerated.