{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T08:42:18Z","timestamp":1792917738830,"version":"4.5.0"},"reference-count":44,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: OCD is a chronic psychiatric disorder, often requiring long-term pharmacological treatment. Although selective serotonin reuptake inhibitors (SSRIs) are considered first-line agents, 40 to 60% of patients show only partial or no response when treated at standard dosages. In such cases, supratherapeutic doses of SSRIs have been proposed as an alternative strategy. However, the evidence supporting this approach remains limited and fragmented. This review aims to evaluate the rationale, clinical efficacy, tolerability, and practical considerations associated with high-dose SSRI use in OCD. Methods: A structured narrative review was conducted using targeted literature searches in PubMed and Scopus. Studies were included if they reported on the use of high-dose SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, or sertraline) in patients with OCD and provided efficacy and\/or tolerability data. Clinical trials, observational studies, and case reports were all reviewed. Results: Evidence shows that higher doses of SSRIs are significantly more effective than low or medium doses in reducing OCD symptoms\u2014especially in individuals who have only partially responded to standard treatment. Smaller clinical studies and case reports have also demonstrated that supratherapeutic dosing, beyond typical regulatory limits, can be both effective and well tolerated in treatment-resistant OCD. Conclusions: High-dose SSRI treatment may be a valuable option for selected OCD patients who do not respond to standard therapy. However, careful patient selection, regular monitoring, and further controlled studies are necessary to better define its long-term safety and effectiveness. In this context, increasingly advanced technologies\u2014such as therapeutic drug monitoring and pharmacogenetic testing for relevant polymorphisms\u2014may support more individualized and safer treatment strategies.<\/jats:p>","DOI":"10.3390\/jcm14113858","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T10:21:49Z","timestamp":1748859709000},"page":"3858","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["When Standard Is Not Enough: A Narrative Review of Supratherapeutic SSRI Doses in Resistant Obsessive Compulsive Disorder"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1008-9915","authenticated-orcid":false,"given":"Giacomo","family":"Gualtieri","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, University of Siena School of Medicine, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9211-5248","authenticated-orcid":false,"given":"Alessandro","family":"Cuomo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Siena School of Medicine, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3002-529X","authenticated-orcid":false,"given":"Simone","family":"Pardossi","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Siena School of Medicine, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5827-0853","authenticated-orcid":false,"given":"Andrea","family":"Fagiolini","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Siena School of Medicine, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1038\/mp.2008.94","article-title":"The Epidemiology of Obsessive-Compulsive Disorder in the National Comorbidity Survey Replication","volume":"15","author":"Ruscio","year":"2010","journal-title":"Mol. 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