Ketamine and esketamine for the prevention of postpartum depression: A systematic review and network meta-analysis, with an integrated evidence synthesis.
Isis Lunsky, Gilmar Gutierrez, Xena Wang, Andrea Zhuang, Yanbo Zhang, Gustavo Vazquez, Venkat Bhat, Shaina Archer, Atul Khullar, Carson Chrenek, Jennifer Swainson
Psychiatry Research May 12, 2026 DOI: 10.1016/j.psychres.2026.117221 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review with network meta-analysis and narrative synthesis Randomized Qualitative Peer reviewed |
|---|---|
| Sample size | 36 |
| Population | Postpartum women |
| Interventions | Ketamine Esketamine |
| Topics | Esketamine Ketamine Depression |
| Keywords | Perinatal mental health Postpartum depression Psychopharmacology |
| Key findings | Ketamine and esketamine treatment may be associated with a reduced risk of developing postpartum depression, but the quality of the data was low to very low. |
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.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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State of the evidence: Esketamine Supports
Ketamine and esketamine treatment may be associated with a reduced risk of developing postpartum depression, but the quality of the data was low to very low.
Synthesized
Comparable studies
Other systematic reviews and meta-analyses on esketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Comparative efficacy of racemic ketamine and esketamine for depression: a systematic review and meta-analysis Adults with unipolar or bipolar major depression | 2020 | Systematic review and meta-analysis | n = 1,877 |
| The acute antisuicidal effects of single-dose intravenous ketamine and intranasal esketamine in individuals with major depression and bipolar disorders: A systematic review and meta-analysis. Participants in randomized controlled trials of ketamine for suicidal ideation | 2020 | Systematic review and meta-analysis | n = 197 |
| Efficacy of Esketamine Augmentation in Major Depressive Disorder Patients with major depressive disorder who are treatment-resistant or acutely suicidal | 2020 | Systematic review and meta-analysis | n = 774 |
| Esketamine Treatment for Depression in Adults: A PRISMA Systematic Review and Meta-Analysis. Patients with treatment-resistant major depressive disorder | 2025 | Systematic review and meta-analysis | |
| EFFICACY AND SAFETY OF RACEMIC KETAMINE AND ESKETAMINE FOR DEPRESSION: A SYSTEMATIC REVIEW AND META-ANALYSIS Adults with unipolar or bipolar major depression | 2022 | Systematic review and meta-analysis | n = 2,903 |