{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:18:15Z","timestamp":1791332295051,"version":"4.3.1"},"reference-count":56,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objective: A substantial proportion of patients with obsessive\u2013compulsive disorder (OCD) does not respond adequately to first-line treatments such as selective serotonin reuptake inhibitors and cognitive-behavioral therapy. OCD has traditionally been conceptualized as a serotonergic disorder. However, emerging evidence suggests that glutamatergic dysfunction plays an important role. Ketamine and esketamine are NMDA receptor antagonists with rapid antidepressant effects and have therefore attracted interest as potential treatments for OCD. This scoping review aims to map and synthesize the existing preclinical and clinical evidence regarding the therapeutic potential of ketamine and esketamine in OCD. Methods: A scoping review methodology based on the Arksey and O\u2019Malley framework and Joanna Briggs Institute guidance was applied. Searches were conducted in PubMed, Scopus, and Web of Science. Studies that examined ketamine or esketamine in OCD populations or relevant experimental models were included. Results: Twenty-one studies met the inclusion criteria, of which five were preclinical studies and sixteen were clinical investigations. Preclinical evidence suggests that ketamine and esketamine improve compulsive-like behaviors. Clinical studies suggest that ketamine can produce rapid reductions in obsessive symptoms, though results remain inconsistent. Most trials evaluated single administrations, while limited evidence suggests that repeated dosing strategies may provide greater clinical benefit. Conclusions: Ketamine and esketamine show promise as rapid acting interventions for OCD, particularly in treatment refractory cases. However, current evidence remains preliminary and heterogeneous. Future research should prioritize adequately powered randomized trials and investigation of repeated administration protocols with longer follow-up periods to determine efficacy and optimal clinical implementation.<\/jats:p>","DOI":"10.3390\/ph19040628","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T10:14:46Z","timestamp":1776334486000},"page":"628","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Ketamine and Esketamine in Obsessive\u2013Compulsive Disorder: A Scoping Review of Clinical and Mechanistic Evidence"],"prefix":"10.3390","volume":"19","author":[{"given":"Maria","family":"Marmureanu","sequence":"first","affiliation":[{"name":"Department of Adult Psychiatry, \u201cProf. Dr. Alexandru Obregia\u201d Clinical Hospital of Psychiatry, 041914 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana Valy","family":"Besoiu","sequence":"additional","affiliation":[{"name":"Department of Social Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"},{"name":"Titan Psychiatric Hospital \u201cDr. Constantin Gorgos\u201d, 030447 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0075-0050","authenticated-orcid":false,"given":"Vlad","family":"Dionisie","sequence":"additional","affiliation":[{"name":"Department of Adult Psychiatry, \u201cProf. Dr. Alexandru Obregia\u201d Clinical Hospital of Psychiatry, 041914 Bucharest, Romania"},{"name":"Department of Psychiatry and Psychology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2492-4529","authenticated-orcid":false,"given":"Mihnea Costin","family":"Manea","sequence":"additional","affiliation":[{"name":"Department of Adult Psychiatry, \u201cProf. Dr. Alexandru Obregia\u201d Clinical Hospital of Psychiatry, 041914 Bucharest, Romania"},{"name":"Department of Psychiatry and Psychology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3111-4089","authenticated-orcid":false,"given":"Catalin","family":"Ple\u0219ea-Condratovici","sequence":"additional","affiliation":[{"name":"Morphological and Functional Sciences Department, Faculty of Medicine and Pharmacy, \u201cDun\u0103rea de Jos\u201d University of Gala\u021bi, 800008 Galati, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sorana Iulia","family":"Voican","sequence":"additional","affiliation":[{"name":"Department of Adult Psychiatry, \u201cProf. Dr. Alexandru Obregia\u201d Clinical Hospital of Psychiatry, 041914 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirela","family":"Manea","sequence":"additional","affiliation":[{"name":"Department of Adult Psychiatry, \u201cProf. Dr. Alexandru Obregia\u201d Clinical Hospital of Psychiatry, 041914 Bucharest, Romania"},{"name":"Department of Psychiatry and Psychology, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 020021 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"58","DOI":"10.4103\/psychiatry.IndianJPsychiatry_520_18","article-title":"Glutamatergic Augmentation Strategies in Obsessive\u2013Compulsive Disorder","volume":"61","author":"Sheshachala","year":"2019","journal-title":"Indian J. 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