Ketamine for the Treatment of Obsessive-Compulsive Disorder (OCD): A Systematic Review on Efficacy and Tolerability.
Isabela Heroiu, Gia Han Le, Maria‐christina Sioufi, Christine E. Dri, Yang Jing Zheng, Sabrina Wong, Roger S McIntyre
Clinical Neuropharmacology June 19, 2026 DOI: 10.1097/wnf.0000000000000692 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Systematic review Randomized Open-label Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Topics | Ketamine Esketamine |
| Keywords | N-methyl-d-aspartate Humans Infusions Obsessive-compulsive disorder |
| Key findings | Ketamine consistently and significantly improved overall obsessive-compulsive disorder symptom severity, with reductions up to 50% to 60%, but the duration of effects varied from a few hours postinfusion to 6 weeks. |
Abstract
This systematic review aims to assess the efficacy and tolerability of ketamine in the treatment of obsessive-compulsive disorder. Obsessive-compulsive disorder is a chronic and severe disorder characterized by intrusive thoughts and repetitive behaviours that can cause significant distress. Notwithstanding current treatments and interventions for obsessive-compulsive disorder, some individuals still do not adequately respond to conventional pharmacotherapeutic and/or psychotherapeutic interventions. Emerging evidence indicates that ketamine, an N-methyl-D-aspartate receptor antagonist, could have potential rapid-acting and enduring efficacy in the treatment of obsessive-compulsive disorder. A systematic search was conducted with OVID, PubMed, and Scopus from database inception to July 2025. Two independent reviewers (I.H. and M.C.S.) screened the studies, assessed methodological quality, and extracted pertinent data. Five studies (3 randomized controlled trials and 2 open-label trials) were deemed eligible for inclusion and included variable routes of administration (intravenous, intramuscular, and oral) and dosing frequencies. Across studies, ketamine consistently and significantly improved overall obsessive-compulsive disorder symptom severity, with reductions up to 50% to 60%; however, the duration of effects varied from a few hours postinfusion to 6 weeks. Overall, ketamine was generally well tolerated. Further research should focus on optimizing ketamine treatment (ie, dosing regimens, routes of administration) for sustained symptom reduction.
Comparable studies
Other systematic reviews and meta-analyses on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis Depressed patients with suicidal ideation at baseline | 2017 | Systematic review and individual participant data meta-analysis | n = 167 |
| Ketamine use: a review Ketamine users | 2011 | Systematic review | |
| Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression Participants with major depression in placebo-controlled, double-blind, randomized... | 2015 | Systematic review and meta-analysis | |
| Ketamine and postoperative pain – a quantitative systematic review of randomised trials Surgical patients from 25 countries | 2004 | Systematic review | n = 2,839 |
| Side-effects associated with ketamine use in depression: a systematic review. Patients with depression | 2018 | Systematic review |
Citations in the library
Cited by 2
- Intranasal Esketamine Augmentation in Treatment-Resistant Obsessive–Compulsive Disorder with Comorbid Treatment-Resistant Depression: A Six-Month Case Report Psychiatry International September 10, 2026
- The effect of ketamine on mitochondrial bioenergetics, viability, and function: A systematic review. Journal of Psychopharmacology September 7, 2026
Cites 14
- Mechanisms of Ketamine Action as an Antidepressant Molecular Psychiatry March 13, 2018
- Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation American Journal of Psychiatry March 17, 2021
- Role of BDNF in the pathophysiology and treatment of depression: Activity‐dependent effects distinguish rapid‐acting antidepressants European Journal of Neuroscience December 6, 2019
- Ketamine as an antidepressant: overview of its mechanisms of action and potential predictive biomarkers Therapeutic Advances in Psychopharmacology 2020
- 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. Journal of Psychiatric Research December 11, 2020
and 9 more in the library