{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T20:43:13Z","timestamp":1775076193517,"version":"3.50.1"},"reference-count":29,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T00:00:00Z","timestamp":1605657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Human Psychopharmacology"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Clozapine is an atypical antipsychotic indicated in patients with treatment\u2010resistant schizophrenia which remains underused due to safety issues. Mechanisms behind these adverse effects are complex and not fully understood. They may involve immune\u2010related mechanisms, direct toxic effects and oxidative stress. Clozapine\u2010induced oxidative stress might indeed notably be involved in the onset of neutropenia, agranulocytosis, myocarditis, sialorrhea, and metabolic alterations. Therefore, the association of N\u2010acetylcysteine (NAC), an easily accessible, low\u2010cost and well tolerated antioxidant drug could be of interest in clozapine\u2010treated patients to improve clozapine safety. Furthermore, according to recent studies NAC could help to improve schizophrenia symptoms. We believe that the use of NAC in the context of clozapine prescribing merits further study, as it could improve clozapine safety which may lead to a wider use and ultimately improve the healthcare of thousands of patients. NAC could also secondarily show positive knock\u2010on effects for the patients by improving clinical symptoms of schizophrenia in synergy with clozapine, and by reducing substance abuse and thus by improving the patient's overall condition. However, given the rarity of clozapine\u2010induced severe adverse effects, only a large volume of data (e.g., National adverse events monitoring) could assess the benefits of NAC on clozapine safety.<\/jats:p>","DOI":"10.1002\/hup.2769","type":"journal-article","created":{"date-parts":[[2020,11,18]],"date-time":"2020-11-18T22:46:41Z","timestamp":1605739601000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Could N\u2010acetylcysteine improve the safety of clozapine?"],"prefix":"10.1002","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7483-2489","authenticated-orcid":false,"given":"Basile","family":"Chr\u00e9tien","sequence":"first","affiliation":[{"name":"Department of Pharmacology Caen University Hospital Caen France"},{"name":"Pharmacovigilance Regional Center Caen University Hospital Caen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sophie","family":"Fedrizzi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Caen University Hospital Caen France"},{"name":"Pharmacovigilance Regional Center Caen University Hospital Caen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V\u00e9ronique","family":"Lelong\u2010Boulouard","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Caen University Hospital Caen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion","family":"Sassier","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Caen University Hospital Caen France"},{"name":"Pharmacovigilance Regional Center Caen University Hospital Caen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"Alexandre","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Caen University Hospital Caen France"},{"name":"Pharmacovigilance Regional Center Caen University Hospital Caen France"},{"name":"Signalisation, \u00e9lectrophysiologie et imagerie des l\u00e9sions d'isch\u00e9mie\u2010reperfusion myocardique Normandie Univ UNICAEN Caen University Hospital Caen France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles","family":"Dolladille","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Caen University Hospital Caen France"},{"name":"Signalisation, \u00e9lectrophysiologie et imagerie des l\u00e9sions d'isch\u00e9mie\u2010reperfusion myocardique Normandie Univ UNICAEN Caen University Hospital Caen France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,11,18]]},"reference":[{"issue":"16","key":"e_1_2_3_2_1","first-page":"253","article-title":"Brain oxidative stress and neurodegeneration in the ketamine model of schizophrenia during antipsychotic Treatment\u202f: Effects of N\u2010acetylcysteine treatment","volume":"6","author":"Abdel\u2010Salam O. 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