{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T13:02:01Z","timestamp":1785589321026,"version":"3.56.0"},"reference-count":44,"publisher":"Georg Thieme Verlag KG","issue":"06","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacopsychiatry"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Clozapine is a recommended treatment for psychotic symptoms in patients with\n                        Parkinson\u2019s disease (PD) and\/or dementia. However, the therapeutic reference\n                        range for clozapine in these patients has not been established hitherto.<\/jats:p>\n                  <jats:p>The study was performed in three university hospitals in Germany and\n                        Switzerland, including clozapine-treated patients with PD and\/or dementia.\n                        The primary outcome was tolerability based on reports of adverse drug\n                        reactions and\/or changes in laboratory tests or electrocardiogram and\/or\n                        clozapine discontinuation. We meta-analyzed demographic and pharmacokinetic\n                        parameters in patients tolerating clozapine well versus not. A meta-analytic\n                        summary receiver operating characteristic (SROC) to establish the clozapine\n                        upper level associated with poor tolerability was estimated.<\/jats:p>\n                  <jats:p>We analyzed a total of 99 patients suffering from PD (56.6%) and\/or dementia\n                        (49.5%) with a mean age of 70.3\u00b19.5 years and 41.4% females; poor\n                        tolerability was reported in 26 of 99 patients (26.3%). When comparing\n                        patients with and without poor tolerability, there were no differences in\n                        age, body mass index, sex, smoking, or clozapine dose, nor did we find\n                        statistically significant differences in clozapine levels (standardized mean\n                        difference 0.46, 95% confidence interval \u2212\u20090.04 to 0.96, p=0.07), and\n                        heterogeneity was low (I2=0.0%). Clozapine blood levels above\n                        193\u2009ng\/mL were associated with poor tolerability (SROC area-under-curve 0.6,\n                        sensitivity 39.7%, specificity 79.9%).<\/jats:p>\n                  <jats:p>One of four patients with PD and\/or dementia treated with clozapine did not\n                        tolerate clozapine well, which was associated with a trend toward elevated\n                        clozapine concentrations. Monitoring drug levels may help to improve\n                        tolerability in these patients.<\/jats:p>","DOI":"10.1055\/a-2560-4028","type":"journal-article","created":{"date-parts":[[2025,4,17]],"date-time":"2025-04-17T19:17:16Z","timestamp":1744917436000},"page":"263-271","source":"Crossref","is-referenced-by-count":4,"title":["Therapeutic Reference Range for Clozapine Plasma Levels in\n                    Parkinson\u2019s Disease or Dementia: A Systematic Review and Individual Participant\n                    Data Meta-analysis"],"prefix":"10.1055","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2699-8422","authenticated-orcid":false,"given":"Nazar","family":"Kuzo","sequence":"additional","affiliation":[{"name":"Department of Adult Psychiatry and Psychotherapy, University Hospital\n                    of Psychiatry Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marianna","family":"Piras","sequence":"additional","affiliation":[{"name":"Unit of Pharmacogenetics and Clinical Psychopharmacology, Center for\n                    Psychiatric Neuroscience, Department of Psychiatry, Lausanne University\n                    Hospital, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich C.","family":"Lutz","sequence":"additional","affiliation":[{"name":"Department of Addiction Therapy and Withdrawal, Clinic Schlo\u00df\n                    Winnenden, Germany"},{"name":"University Hospital of Psychiatry and Psychotherapy, T\u00fcbingen,\n                    Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehard","family":"Haen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Clinical Pharmacology,\n                    University of Regensburg, Germany"},{"name":"Department of Pharmacology and Toxicology, University of Regensburg,\n                    Germany"},{"name":"Clinical Pharmacology, Institute AGATE gGmbH, Pentling,\n                    Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin B.","family":"Eap","sequence":"additional","affiliation":[{"name":"Unit of Pharmacogenetics and Clinical Psychopharmacology, Center for\n                    Psychiatric Neuroscience, Department of Psychiatry, Lausanne University\n                    Hospital, Switzerland"},{"name":"School of Pharmaceutical Sciences, University of Geneva,\n                    Switzerland"},{"name":"Center for Research and Innovation in Clinical Pharmaceutical Sciences,\n                    Lausanne University Hospital, Switzerland"},{"name":"Institute of Pharmaceutical Sciences of Western Switzerland, University\n                    of Geneva, University of Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Hiemke","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, University Medical Center\n                    of Mainz, Germany"},{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University\n                    Medical Center of Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Paulzen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen\n                    University, and JARA \u2013 Translational Brain Medicine, Aachen,\n                    Germany"},{"name":"Alexianer Center for Mental Health Aachen, Aachen,\n                    Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Schoretsanitis","sequence":"additional","affiliation":[{"name":"Department of Adult Psychiatry and Psychotherapy, University Hospital\n                    of Psychiatry Zurich, Switzerland"},{"name":"The Zucker Hillside Hospital, Department of Psychiatry Research,\n                    Northwell Health, Glen Oaks, New York, USA"},{"name":"Department of Psychiatry, Zucker School of Medicine at\n                    Northwell\/Hofstra, Hempstead, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2025,4,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1007\/S00415-010-5465-Z","article-title":"Frequency of dementia, depression, and other neuropsychiatric symptoms in 1,449\n                    outpatients with Parkinson\u2019s disease","volume":"257","author":"O Riedel","year":"2010","journal-title":"J Neurol"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1097\/JGP.0B013E31821F1B41","article-title":"Prevalence of psychotic symptoms in a community-based 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Psychiatry"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1093\/BRAIN\/AWAA413","article-title":"Psychosis in neurodegenerative disease: Differential patterns of hallucination\n                    and delusion symptoms","volume":"144","author":"G Naasan","year":"2021","journal-title":"Brain"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/J.JAGP.2015.12.006","article-title":"The impact of psychotic symptoms on the persons with dementia experiencing\n                    them","volume":"24","author":"J Cohen-Mansfield","year":"2016","journal-title":"Am J Geriatr Psychiatry"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/J.JAGP.2014.01.008","article-title":"Challenges of the treatment of neuropsychiatric symptoms associated with\n                    dementia","volume":"22","author":"B H Mulsant","year":"2014","journal-title":"Am J Geriatr 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Pollak","year":"2004","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/J.EURONEURO.2006.08.007","article-title":"Treating dopamimetic psychosis in Parkinson\u2019s disease: Structured review and\n                    meta-analysis","volume":"17","author":"H Frieling","year":"2007","journal-title":"Eur Neuropsychopharmacol"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.3390\/IJERPH19010364","article-title":"Systematic review on Parkinson\u2019s disease medications, emphasizing on three\n                    recently approved drugs to control Parkinson\u2019s symptoms","volume":"19","author":"P Sivanandy","year":"2021","journal-title":"Int J Environ Res Public Health"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1097\/JCP.0000000000001678","article-title":"Escaping the long shadow cast by agranulocytosis: Reflections on clozapine\n                    pharmacovigilance 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A literature review, five new cases and a proposed\n                    definition","volume":"268","author":"G Schoretsanitis","year":"2024","journal-title":"Schizophr Res"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.1186\/S12877-022-03235-9","article-title":"Anti-cholinergic drug burden in patients with dementia increases after hospital\n                    admission: A multicentre cross-sectional study","volume":"22","author":"A Hook","year":"2022","journal-title":"BMC Geriatr"}],"container-title":["Pharmacopsychiatry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2560-4028.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T23:35:42Z","timestamp":1762299342000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2560-4028"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,17]]},"references-count":44,"journal-issue":{"issue":"06","published-online":{"date-parts":[[2025,11,4]]},"published-print":{"date-parts":[[2025,11]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2560-4028","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0176-3679","1439-0795"],"issn-type":[{"value":"0176-3679","type":"print"},{"value":"1439-0795","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,17]]}}}