Ketamine for the Treatment of Obsessive-Compulsive Disorder (OCD): A Systematic Review on Efficacy and Tolerability

OBJECTIVES: This systematic review aims to assess the efficacy and tolerability of ketamine in the treatment of obsessive-compulsive disorder. BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Further research should focus on optimizing ketamine treatment (ie, dosing regimens, routes of administration) for sustained symptom reduction.