{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T23:07:49Z","timestamp":1779318469163,"version":"3.51.4"},"reference-count":27,"publisher":"Georg Thieme Verlag KG","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacopsychiatry"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Clozapine is an effective antipsychotic used in treatment-resistant schizophrenia, but high serum levels may increase side effects. This study aimed to examine the efficacy and tolerability profile of clozapine in a naturalistic setting. The impact of multiple factors, specifically CYP1A2 genotypes, smoking, and fluvoxamine coadministration, on CYP1A2 enzyme activity was assessed as a secondary exploratory end point.<\/jats:p>\n                  <jats:p>In this prospective, observational study, 32 patients receiving stable clozapine therapy were observed over a 24-hour period at the Central Institute for Mental Health, Mannheim. Clozapine blood levels were measured via liquid chromatography\u2013mass spectrometry and the MyCare Clozapine Assay.<\/jats:p>\n                  <jats:p>Clozapine levels above 600 ng\/mL were not associated with increased clinical efficacy but were linked to more side effects. Sleep quality was generally poor, and daytime sedation was frequent. While coadministration with the CYP1A2 inhibitor fluvoxamine led to a dose-corrected increase in clozapine levels of approximately 50%; smoking reduced clozapine (\u221236%) and norclozapine (\u221232%) levels.<\/jats:p>\n                  <jats:p>Clozapine levels above the therapeutic reference range may not provide additional benefits and could increase side effects. Therapeutic drug monitoring is an essential clinical practice tool, especially when using comedication or in smokers. Overall, these findings should be interpreted as exploratory and supportive of existing therapeutic guidance because of the small sample size and naturalistic study design.<\/jats:p>","DOI":"10.1055\/a-2868-3000","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T22:41:36Z","timestamp":1779316896000},"source":"Crossref","is-referenced-by-count":0,"title":["High Clozapine Serum Levels Do Not Improve Response: An Observational Study in Patients with Schizophrenia Treated with Clozapine in a Naturalistic Setting"],"prefix":"10.1055","author":[{"given":"Xenia M.","family":"Hart","sequence":"additional","affiliation":[{"name":"Heidelberg University, BW, Germany","place":["Mannheim"],"department":["Central Institute of Mental Health, Medical Faculty Mannheim"]},{"name":"Keio University School of Medicine, Japan","place":["Tokyo"],"department":["Department of Neuropsychiatry"]},{"name":"partner site Mannheim\u2014Heidelberg\u2014Ulm, BW, 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