Ketamine and Esketamine in Obsessive-Compulsive Disorder: A Scoping Review of Clinical and Mechanistic Evidence.
Pharmaceuticals (Basel, Switzerland) April 16, 2026 Maria Marmureanu, Mariana Valy Besoiu, Vlad Dionisie et al.
A substantial proportion of patients with obsessive-compulsive disorder (OCD) do not respond to first-line treatments. Ketamine and esketamine, NMDA receptor antagonists with rapid antidepressant effects, have attracted interest as potential treatments. This scoping review of 21 studies (5 preclinical, 16 clinical) found that preclinical evidence suggests ketamine and esketamine improve compulsive-like behaviors. Clinical studies suggest ketamine can produce rapid reductions in obsessive symptoms, though results remain inconsistent. Most trials evaluated single administrations; limited evidence suggests repeated dosing may provide greater benefit. The evidence remains preliminary and heterogeneous, and future research should prioritize adequately powered randomized trials with repeated dosing and longer follow-up.