{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T10:36:58Z","timestamp":1771929418016,"version":"3.50.1"},"reference-count":15,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Psychiatry"],"abstract":"\n Importance<\/jats:title>\n Obsessive-compulsive disorder (OCD) remains treatment-resistant in 40-60% of patients despite adequate trials of serotonin reuptake inhibitors and cognitive behavioral therapy. Glutamatergic dysfunction in cortico-striato-thalamo-cortical circuits has emerged as a key pathophysiologic mechanism, prompting investigation of glutamatergic modulators as augmentation strategies.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the safety, tolerability, and preliminary efficacy of agmatine sulfate augmentation in treatment-resistant OCD.<\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n Prospective open-label case series conducted between May 2025 and November 2025.<\/jats:p>\n <\/jats:sec>\n \n Setting<\/jats:title>\n Outpatient psychiatry practice.<\/jats:p>\n <\/jats:sec>\n \n Participants<\/jats:title>\n Five adults (ages 28\u201354 years) with treatment-resistant OCD who had failed multiple serotonin reuptake inhibitor trials and at least one augmentation strategy.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n All patients were treated with agmatine sulfate initiated at 650 mg daily, increased to 1300 mg daily after one week, as augmentation to stable doses of selective serotonin reuptake inhibitors.<\/jats:p>\n <\/jats:sec>\n \n Main outcomes and measures<\/jats:title>\n We measured the OCD severity using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores assessed at baseline and multiple time points over 112 days. Primary outcome was change in Y-BOCS score from baseline.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Exponential decay modeling revealed gradual symptom reduction with half-life of 16.4 days. Two of five patients (40%) demonstrated clinically meaningful improvement (\u226525% Y-BOCS reduction). Agmatine was well-tolerated with no discontinuations due to adverse effects. Mild transient gastrointestinal symptoms occurred in two patients.<\/jats:p>\n <\/jats:sec>\n \n Conclusions and relevance<\/jats:title>\n This case series provides preliminary, early evidence supporting agmatine\u2019s safety and potential efficacy as augmentation therapy in treatment-resistant OCD. The gradual response pattern and 40% responder rate warrant controlled trials to definitively establish efficacy and identify predictors of treatment response.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fpsyt.2026.1745041","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T06:47:19Z","timestamp":1770187639000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Agmatine augmentation in treatment-resistant obsessive-compulsive disorder: a prospective open-label case series"],"prefix":"10.3389","volume":"17","author":[{"given":"Joshua D.","family":"Salvi","sequence":"first","affiliation":[{"name":"Center for OCD and Related Disorders, Department of Psychiatry, Massachusetts General Hospital","place":["Boston, MA, United States"]},{"name":"Department of Psychiatry, Harvard Medical School","place":["Boston, MA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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 Psychiatry"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145702002900","article-title":"Treatment non-response in OCD: methodological issues and operational definitions","volume":"5","author":"Pallanti","year":"2002","journal-title":"Int J Neuropsychopharmacol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3310\/hta20430","article-title":"A systematic review of the clinical effectiveness and cost-effectiveness of pharmacological and psychological interventions for the management of obsessive-compulsive disorder in children\/adolescents and adults","volume":"20","author":"Skapinakis","year":"2016","journal-title":"Health Technol Assess"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4001823","article-title":"A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder","volume":"11","author":"Bloch","year":"2006","journal-title":"Mol Psychiatry"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2011.09.006","article-title":"Glutamate abnormalities in obsessive compulsive disorder: neurobiology, pathophysiology, and treatment","volume":"132","author":"Pittenger","year":"2011","journal-title":"Pharmacol Ther"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2011.10.007","article-title":"The role of glutamate signaling in the pathogenesis and treatment of obsessive-compulsive disorder","volume":"100","author":"Wu","year":"2012","journal-title":"Pharmacol Biochem Behav"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32137","article-title":"Meta-analysis of association between obsessive-compulsive disorder and the 3\u2019 region of neuronal glutamate transporter gene SLC1A1","author":"Stewart","year":"2013","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e2451234","DOI":"10.1001\/jamanetworkopen.2024.52963","article-title":"Glutamatergic medications for obsessive-compulsive and related disorders: a systematic review and meta-analysis","volume":"8","author":"Coelho","year":"2025","journal-title":"JAMA Netw Open"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2012.09.015","article-title":"Memantine add-on in moderate to severe obsessive-compulsive disorder: randomized double-blind placebo-controlled study","volume":"47","author":"Ghaleiha","year":"2013","journal-title":"J Psychiatr Res"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2009.60","article-title":"N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study","volume":"66","author":"Grant","year":"2009","journal-title":"Arch Gen Psychiatry"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(24)37988-1","article-title":"Agmatine selectively blocks the N-methyl-D-aspartate subclass of glutamate receptor channels in rat hippocampal neurons","volume":"288","author":"Yang","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2016.03.009","article-title":"Agmatine produces antidepressant-like effects by activating AMPA receptors and mTOR signaling","volume":"26","author":"Freitas","year":"2016","journal-title":"Eur Neuropsychopharmacol"},{"key":"B13","article-title":"Involvement of nitric oxide in anticompulsive-like effect of agmatine on marble-burying behaviour in mice","volume":"770","author":"Kotagale","year":"2015","journal-title":"Eur J Pharmacol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2006.05.016","article-title":"Putrescine produces antidepressant-like effects in the forced swimming test and in the tail suspension test in mice","volume":"30","author":"Zomkowski","year":"2006","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1089\/jmf.2014.0026","article-title":"Long-term (5 years), high daily dosage of dietary agmatine\u2014evidence of safety: a case report","volume":"17","author":"Gilad","year":"2014","journal-title":"J Med Food"}],"container-title":["Frontiers in Psychiatry"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2026.1745041\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T09:56:10Z","timestamp":1771926970000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fpsyt.2026.1745041\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,4]]},"references-count":15,"alternative-id":["10.3389\/fpsyt.2026.1745041"],"URL":"https:\/\/doi.org\/10.3389\/fpsyt.2026.1745041","relation":{},"ISSN":["1664-0640"],"issn-type":[{"value":"1664-0640","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,4]]},"article-number":"1745041"}}