Meta-analysis · 2026
Comparing drug treatments for postpartum depression, including esketamine
- Original title
- Comparative efficacy and acceptability of pharmacological interventions for postpartum depression: a systematic review and network meta-analysis.
- Authors
- Xiao Y, Xie P, Li D, et al.
- Journal
- Psychiatry research, 2026
- Molecules
- Esketamine
- Conditions
- Postpartum depression
- Participants
- 1722
- Evidence grade
- Moderate
- Source
- Read the original paper
The question
Which drug treatments work best for postpartum depression, and how well are they tolerated?
What they did
Researchers gathered randomized controlled trials of medications for postpartum depression and combined them using a network meta-analysis, a method that compares treatments both directly and indirectly through their shared comparisons with placebo. Two reviewers independently pulled the data and judged how reliable each trial was. Eighteen trials with 1,722 participants in total were included. The treatments covered conventional antidepressants, rapid-acting glutamate drugs such as esketamine, neuroactive steroids, hormones and a botanical preparation.
What they found
Compared with placebo, five treatments showed signals of reduced depression severity: saffron (standardized mean difference -1.07, 95% confidence interval -1.52 to -0.61), fluoxetine (-0.95, -1.43 to -0.47), esketamine (-0.63, -0.89 to -0.37), brexanolone and zuranolone. Fluoxetine, saffron and zuranolone were linked to higher response rates, though the fluoxetine and saffron estimates were imprecise. Brexanolone was the only treatment with a statistically significant improvement in remission, but it also showed a possibly unfavourable signal for acceptability, based on how many people stopped treatment for any reason. Zuranolone was associated with more adverse events.
The fine print
The authors themselves flag sparse evidence networks, few head-to-head comparisons between active drugs, imprecise estimates and clinical differences between trials. Rankings of treatments were described as exploratory and should not be read as a definitive order. Total pooled sample was modest for the number of treatments compared, and this summary is based on the abstract alone.
What it means
Several drug options, including esketamine, showed signals of benefit for postpartum depression in randomized trials, but the comparisons between them remain uncertain and each option carries its own tolerability trade-offs.
Evidence grade: Moderate. A network meta-analysis pooling only randomized trials, but the evidence networks were sparse and the certainty of evidence was mostly low to moderate.
This summary is based on the study’s published abstract.