Short-term effects of oral ketamine for the treatment of depression: A systematic review and meta-analysis of randomized controlled trials.
Sonia Shenoy, Vijetha Shenoy Belle, Ravindra Neelakanthappa Munoli, Meha Sharma, Samir Kumar Praharaj
Asian Journal of Psychiatry May 16, 2026 DOI: 10.1016/j.ajp.2026.105014 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review and meta-analysis Randomized Peer reviewed |
|---|---|
| Sample size | 414 |
| Population | Patients with unipolar depression, bipolar depression, or treatment-resistant depression |
| Intervention | Oral ketamine |
| Topics | Depression Ketamine Esketamine |
| Keywords | Humans Antidepressive agents Administration, oral Depressive disorder, treatment-resistant Meta-analysis Systematic review Oral ketamine |
| Citations | 1 |
| Key findings | Oral ketamine significantly reduced depression scores compared with placebo (standardized mean difference -0.62) and increased remission (risk ratio 2.38), with no significant difference versus other forms of ketamine (mean difference 0.28). The authors suggest oral ketamine may be effective and safe, but call for further randomized trials. |
Abstract
Background: Oral ketamine is a novel treatment for management of depression. However, evidence related to its effectiveness and safety is unavailable. This systematic review aimed to assess the short-term efficacy and safety of oral ketamine compared to placebo or other modes of ketamine in randomized controlled trials (RCT) in unipolar depression, bipolar depression, and treatment-resistant depression.
Methods: A comprehensive search was done for RCTs in multiple databases including PubMed, EMBASE, Scopus, Cochrane Central, Web of Science and ProQuest. The primary outcome was change in depression scores measured by validated scales. Meta-analysis was carried out using random-effects model.
Results: Eight studies (n = 414) were included. The depression scores showed a significant decrease after oral ketamine treatment versus placebo, with a SMD of - 0.62 [95% CI= -0.39, -0.85, Z = 5.24, p < 0.00001] with moderate certainty of the evidence. A significant difference in remission outcome favouring ketamine was observed with a pooled RR of 2.38 [95% CI= 1.19, 4.77, p = 0.01] with no heterogeneity [I2 = 0%, p = 0.49].Compared to other forms of ketamine, depression scores showed no significant difference between oral ketamine treatment versus other forms of ketamine, with a MD of 0.28 [95% CI= -4.58, 5.14, p = 0.91]. Oral ketamine was well-tolerated with no serious adverse events.
Conclusion: The findings of our study suggest that oral ketamine can be safely applied and may be effective in reducing depressive symptoms in patients with depression. Further RCTs are needed to strengthen our results and identify the optimal treatment duration parameters.
Comparable studies
Other systematic reviews and meta-analyses on ketamine for depression, most cited first.
Citations in the library
Cites 16
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- A Phase 2 Open Label Study of Efficacy, Safety, and Tolerability of SLS-002 (Intranasal Racemic Ketamine) in Adults with MDD at Imminent Risk of Suicide. Psychopharmacology Bulletin March 4, 2024
- Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers Therapeutic Advances in Psychopharmacology 2020
- Ketamine for Depression, 4: In What Dose, at What Rate, by What Route, for How Long, and at What Frequency? The Journal of Clinical Psychiatry July 20, 2017
- Repeated oral ketamine for out-patient treatment of resistant depression: randomised, double-blind, placebo-controlled, proof-of-concept study The British Journal of Psychiatry September 24, 2018
and 11 more in the library