{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:45:49Z","timestamp":1792273549203,"version":"4.4.0"},"reference-count":126,"publisher":"Georg Thieme Verlag KG","issue":"02","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacopsychiatry"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600\u2009ng\/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas\u2019 original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350\u2009ng\/mL. In the US, daily doses of 300\u2013600\u2009mg\/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75\u2013150\u2009mg\/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175\u2013300\u2009mg\/day, 3) European\/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100\u2013200\u2009mg\/day, 4) European\/Western Asian ancestry with average metabolism needing 250\u2013400\u2009mg\/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150\u2013300\u2009mg\/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300\u2013600\u2009mg\/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.<\/jats:p>","DOI":"10.1055\/a-1625-6388","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T19:27:40Z","timestamp":1639596460000},"page":"73-86","source":"Crossref","is-referenced-by-count":242,"title":["An International Adult Guideline for Making Clozapine Titration Safer by Using Six Ancestry-Based Personalized Dosing Titrations, CRP, and Clozapine Levels"],"prefix":"10.1055","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7756-2314","authenticated-orcid":false,"given":"Jose","family":"de Leon","sequence":"additional","affiliation":[{"name":"Mental Health Research Center, Eastern State Hospital, Lexington, KY, USA"},{"name":"Department of Psychiatry, University of Kentucky, Lexington, KY, USA"},{"name":"Psychiatry and Neurosciences Research Group (CTS-549), Institute of Neurosciences, University of Granada, Granada, Spain"},{"name":"Biomedical Research Centre in Mental Health Net (CIBERSAM), Santiago Apostol Hospital, University of the Basque Country, Vitoria, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3851-4117","authenticated-orcid":false,"given":"Georgios","family":"Schoretsanitis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Z\u00fcrich, Z\u00fcrich, Switzerland"},{"name":"The Zucker Hillside Hospital, Psychiatry Research, Northwell Health, Glen Oaks, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6789-7076","authenticated-orcid":false,"given":"Robert L.","family":"Smith","sequence":"additional","affiliation":[{"name":"Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6190-2751","authenticated-orcid":false,"given":"Espen","family":"Molden","sequence":"additional","affiliation":[{"name":"Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway"},{"name":"Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, University of Oslo, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0625-711X","authenticated-orcid":false,"given":"Anssi","family":"Solismaa","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland"},{"name":"Department of Psychiatry, Tampere University Hospital, Tampere, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6855-1226","authenticated-orcid":false,"given":"Niko","family":"Sepp\u00e4l\u00e4","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Satasairaala, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0576-6887","authenticated-orcid":false,"given":"Miloslav","family":"Kope\u010dek","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health, Klecany, Czech Republic"},{"name":"Department of Psychiatry, Charles University, Third Faculty of Medicine, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6734-6936","authenticated-orcid":false,"given":"Patrik","family":"\u0160vancer","sequence":"additional","affiliation":[{"name":"National Institute of Mental Health, Klecany, Czech Republic"},{"name":"Department of Psychiatry, Charles University, Third Faculty of Medicine, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3074-7637","authenticated-orcid":false,"given":"Ismael","family":"Olmos","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit and Pharmacy Department, Vilardeb\u00f3 Hospital, Administraci\u00f3n de Servicios de Salud, Montevideo, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6623-0632","authenticated-orcid":false,"given":"Carina","family":"Ricciardi","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Unit and Outpatient Clinic, Vilardeb\u00f3 Hospital, Administraci\u00f3n de Servicios de Salud, Montevideo, Uruguay"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5064-0095","authenticated-orcid":false,"given":"Celso","family":"Iglesias-Garcia","sequence":"additional","affiliation":[{"name":"Universidad de Oviedo. 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1998-2005","volume":"167","author":"T J Moore","year":"2007","journal-title":"Arch Intern Med"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/schbul\/sbz093","article-title":"Data from the World Health Organization's pharmacovigilance database supports the prominent role of pneumonia in mortality associated with clozapine adverse drug reactions","volume":"46","author":"J de Leon","year":"2020","journal-title":"Schizophr Bull"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/wps.20707","article-title":"Pneumonia may be more frequent and have more fatal outcomes with clozapine than with other second-generation antipsychotics","volume":"19","author":"J de Leon","year":"2020","journal-title":"World Psychiatry"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1111\/acps.13142","article-title":"Antipsychotic medication exposure, clozapine, and pneumonia: results from a self-controlled 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Hematol"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1177\/0004867414554269","article-title":"Clozapine-induced myocarditis: separating the wheat from the chaff","volume":"49","author":"K Winckel","year":"2015","journal-title":"Aust N Z J Psychiatry"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"458","DOI":"10.3109\/00048674.2011.572852","article-title":"A new monitoring protocol for clozapine-induced myocarditis based on an analysis of 75 cases and 94 controls","volume":"45","author":"K J Ronaldson","year":"2011","journal-title":"Aust NZ J Psychiatry"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.schres.2012.08.018","article-title":"Rapid clozapine dose titration and concomitant sodium valproate increase the risk of myocarditis with clozapine: a case-control study","volume":"141","author":"K J Ronaldson","year":"2012","journal-title":"Schizophr Res"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"863","DOI":"10.3390\/ijms17060863","article-title":"Prevalence and predictors of clozapine-associated constipation: a systematic review and meta-analysis","volume":"17","author":"A Shirazi","year":"2016","journal-title":"Int J Mol Sci"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.genhosppsych.2017.02.004","article-title":"Clozapine induced gastrointestinal hypomotility: a potentially life threatening adverse event. A review of the literature","volume":"46","author":"S West","year":"2017","journal-title":"Gen Hosp Psychiatry"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1007\/s40263-017-0481-5","article-title":"Clozapine and gastrointestinal hypomotility","volume":"31","author":"D Cohen","year":"2017","journal-title":"CNS Drugs"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"e12384","DOI":"10.1111\/appy.12384","article-title":"Using therapeutic drug monitoring to personalize clozapine dosing in Asians","volume":"12","author":"J de Leon","year":"2020","journal-title":"Asia Pac Psychiatry"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1517\/17425255.2014.885504","article-title":"Clinically relevant interactions between newer antidepressants and second-generation antipsychotics","volume":"10","author":"E Spina","year":"2014","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"2247","DOI":"10.1212\/WNL.44.12.2247","article-title":"Clozapine-related seizures: experience with 5,629 patients","volume":"44","author":"S V Pacia","year":"1994","journal-title":"Neurology"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1186\/1471-244X-14-75","article-title":"The prevalence of psychosis in epilepsy; a systematic review and meta-analysis","volume":"14","author":"M J Clancy","year":"2014","journal-title":"BMC Psychiatry"},{"key":"ref44","first-page":"CD006633","article-title":"Clozapine versus other atypical antipsychotics for schizophrenia","author":"C Asenjo Lobos","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"611","DOI":"10.2174\/138920011796504473","article-title":"Age-related changes in pharmacodynamics: focus on drugs acting on central nervous and cardiovascular systems","volume":"12","author":"G Trifir\u00f2","year":"2011","journal-title":"Curr Drug Metab"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"603","DOI":"10.4088\/JCP.12r08064","article-title":"Termination of clozapine treatment due to medical reasons: when is it warranted and how can it be avoided?","volume":"74","author":"J Nielsen","year":"2013","journal-title":"J Clin Psychiatry"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.ridd.2005.05.002","article-title":"Guidelines for the use of clozapine in individuals with developmental disabilities","volume":"27","author":"M Sabaawi","year":"2006","journal-title":"Res Dev Disabil"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1111\/j.1365-2125.1994.tb04385.x","article-title":"Clozapine disposition covaries with CYP1A2 activity determined by a caffeine test","volume":"38","author":"L Bertilsson","year":"1994","journal-title":"Br J Clin Pharmacol"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s00228-007-0288-2","article-title":"Comparisons of CYP1A2 genetic polymorphisms, enzyme activity and the genotype-phenotype relationship in Swedes and Koreans","volume":"63","author":"R Ghotbi","year":"2007","journal-title":"Eur J Clin Pharmacol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1016\/S0006-3223(97)00531-3","article-title":"Relationship between patient variables and plasma clozapine concentrations: a dosing nomogram","volume":"44","author":"P J Perry","year":"1998","journal-title":"Biol Psychiatry"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1007\/s00228-006-0209-9","article-title":"The effect of variable cigarette consumption on the interaction with clozapine and olanzapine","volume":"62","author":"T Haslemo","year":"2006","journal-title":"Eur J Clin Pharmacol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/clpt.2011.70","article-title":"Impact of smoking, smoking cessation, and genetic polymorphisms on CYP1A2 activity and inducibility","volume":"90","author":"M Dobrinas","year":"2011","journal-title":"Clin Pharmacol Ther"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1111\/acps.13228","article-title":"Impact of smoking behavior on clozapine blood levels - a systematic review and meta-analysis","volume":"142","author":"E Wagner","year":"2020","journal-title":"Acta Psychiatr Scand"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1177\/00912700122010717","article-title":"Contributions of five human cytochrome P450 isoforms to the N-demethylation of clozapine in vitro at low and high concentrations","volume":"41","author":"O V Olesen","year":"2001","journal-title":"J Clin Pharmacol"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1080\/17512433.2019.1617695","article-title":"Comprehensive review of the clinical utility of and a combined analysis of the clozapine\/norclozapine ratio in therapeutic drug monitoring for adult patients","volume":"12","author":"G Schoretsanitis","year":"2019","journal-title":"Expert Rev Clin Pharmacol"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/S0278-5846(98)00035-9","article-title":"Reversible metabolism of clozapine and clozapine N-oxide in schizophrenic patients","volume":"22","author":"W H Chang","year":"1998","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1017\/S1461145703003249","article-title":"Glucuronidation enzymes, genes and psychiatry","volume":"6","author":"J de Leon","year":"2003","journal-title":"Int J Neuropsychopharmacol"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1124\/dmd.112.050278","article-title":"Which metabolites circulate?","volume":"41","author":"C M Loi","year":"2013","journal-title":"Drug Metab Dispos"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1046\/j.1365-2125.1998.00822.x","article-title":"Pharmacokinetics of clozapine and its metabolites in psychiatric patients: Plasma protein binding and renal clearance","volume":"46","author":"G Schaber","year":"1998","journal-title":"Br J Clin Pharmacol"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/0922-4106(93)90126-T","article-title":"Clozapine and N-desmethylclozapine are potent 5-HT1C receptor antagonists","volume":"245","author":"M Kuoppam\u00e4ki","year":"1993","journal-title":"Eur J Pharmacol"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1097\/JCP.0000000000001018","article-title":"Clozapine metabolism in East Asians and Caucasians: a pilot exploration of the prevalence of poor metabolizers and a systematic review","volume":"39","author":"C J Ruan","year":"2019","journal-title":"J Clin Psychopharmacol"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1097\/00007691-199408000-00006","article-title":"Fluvoxamine inhibition and carbamazepine induction of the metabolism of clozapine: evidence from therapeutic drug monitoring service","volume":"16","author":"M Jerling","year":"1994","journal-title":"Ther Drug Monit"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"439","DOI":"10.3390\/ph13120439","article-title":"Clinically relevant interactions between atypical antipsychotics and anti-infective agents","volume":"13","author":"E Spina","year":"2020","journal-title":"Pharmaceuticals (Basel)"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1159\/000506355","article-title":"Around 3% of 1,300 levels were elevated during infections in a retrospective review of 131 Beijing hospital in-patients with more than 24,000 days of clozapine treatment","volume":"89","author":"C J Ruan","year":"2020","journal-title":"Psychother Psychosom"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1176\/appi.ps.55.5.491","article-title":"Atypical antipsychotic dosing: the effect of smoking and caffeine","volume":"55","author":"J de Leon","year":"2004","journal-title":"Psychiatr Serv"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.clpt.2004.04.003","article-title":"Time response of cytochrome P450 1A2 activity on cessation of heavy smoking","volume":"76","author":"M S Faber","year":"2004","journal-title":"Clin Pharmacol Ther"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1097\/JCP.0000000000001125","article-title":"Exploring the prevalence of clozapine phenotypic poor metabolizers in 4 Asian samples: they ranged between 2% and 13","volume":"39","author":"C J Ruan","year":"2019","journal-title":"J Clin Psychopharmacol"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1097\/FTD.0000000000000705","article-title":"Future studies on the interaction between clozapine and valproic acid should aspire to include longitudinal designs and free valproate concentrations, and should consider that inducer and\/or inhibitory effects may vary with time, the individual, and the auto-induction of valproic acid","volume":"42","author":"J de Leon","year":"2020","journal-title":"Ther Drug Monit"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1097\/00007691-199906000-00017","article-title":"Small effects of valproic acid on the plasma concentrations of clozapine and its major metabolites in patients with schizophrenic or affective disorders","volume":"21","author":"G Facciol\u00e0","year":"1999","journal-title":"Ther Drug Monit"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.pnpbp.2005.10.008","article-title":"Plasma clozapine levels and clinical response in treatment-refractory Chinese schizophrenic patients","volume":"30","author":"J O Wong","year":"2006","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"ref72","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1055\/s-2007-1004591","article-title":"Estimating the size of the effects of co-medications on plasma clozapine concentrations using a model that controls for clozapine doses and confounding variables","volume":"41","author":"F J Diaz","year":"2008","journal-title":"Pharmacopsychiatry"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1097\/YIC.0b013e32835ac9da","article-title":"Clinical predictors of serum clozapine levels in patients with treatment-resistant schizophrenia","volume":"28","author":"A P Rajkumar","year":"2013","journal-title":"Int Clin Psychopharmacol"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1097\/FTD.0b013e3181c0590e","article-title":"Effect of valproate on olanzapine plasma concentrations in patients with bipolar or schizoaffective disorder","volume":"31","author":"E Spina","year":"2009","journal-title":"Ther Drug Monit"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1097\/JCP.0000000000000926","article-title":"The effect of body weight changes on total plasma clozapine concentrations determined by applying a statistical model to the data from a double-blind trial","volume":"38","author":"F J Diaz","year":"2018","journal-title":"J Clin Psychopharmacol"},{"key":"ref76","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1177\/0269881120985166","article-title":"Body mass index as a determinant of clozapine plasma concentrations: A pharmacokinetic-based hypothesis","volume":"35","author":"M Kuzin","year":"2021","journal-title":"J Psychopharmacol"},{"key":"ref77","doi-asserted-by":"crossref","first-page":"2905","DOI":"10.1007\/s00394-020-02421-y","article-title":"The effect of obesity, macronutrients, fasting and nutritional status on drug-metabolizing cytochrome P450s: a systematic review of current evidence on human studies","volume":"60","author":"M Zarezadeh","year":"2021","journal-title":"Eur J Nutr"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"514","DOI":"10.3390\/ph14060514","article-title":"Therapeutic drug monitoring of second- and third-generation antipsychotic drugs-influence of smoking behavior and inflammation on pharmacokinetics","volume":"14","author":"N Moschny","year":"2021","journal-title":"Pharmaceuticals (Basel)"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.schres.2017.03.045","article-title":"Elevated clozapine levels associated with infection: A systematic review","volume":"192","author":"S R Clark","year":"2018","journal-title":"Schizophr Res"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/nature21347","article-title":"Tracing the peopling of the world through genomics","volume":"541","author":"R Nielsen","year":"2017","journal-title":"Nature"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"4","DOI":"10.4103\/IJPSYM.IJPSYM_379_19","article-title":"Do Asian patients require only half of the clozapine dose prescribed for Caucasians? A critical overview","volume":"42","author":"J de Leon","year":"2020","journal-title":"Indian J Psychol Med"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.schres.2020.05.057","article-title":"Do Indian patients with schizophrenia need half the recommended clozapine dose to achieve therapeutic serum level? An exploratory study","volume":"222","author":"S Suhas","year":"2020","journal-title":"Schizophr Res"},{"key":"ref84","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ebiom.2017.11.030","article-title":"Steady-state clozapine and norclozapine pharmacokinetics in Maori and European patients","volume":"27","author":"D B Menkes","year":"2018","journal-title":"EBioMedicine"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s13318-021-00673-5","article-title":"The impact of smoking, sex, infection, and comedication administration on oral olanzapine: a population pharmacokinetic model in Chinese psychiatric patients","volume":"46","author":"Y N Zang","year":"2021","journal-title":"Eur J Drug Metab Pharmacokinet"},{"key":"ref86","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1046\/j.1365-2125.2003.01857.x","article-title":"Olanzapine pharmacokinetics are similar in Chinese and Caucasian subjects","volume":"56","author":"K Sathirakul","year":"2003","journal-title":"Br J Clin Pharmacol"},{"key":"ref87","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1177\/0091270007310385","article-title":"Sex, race, and smoking impact olanzapine exposure","volume":"48","author":"K L Bigos","year":"2008","journal-title":"J Clin Pharmacol"},{"key":"ref88","doi-asserted-by":"crossref","first-page":"369","DOI":"10.2217\/pgs-2020-0015","article-title":"Is there a future for CYP1A2 pharmacogenetics in the optimal dosing of clozapine?","volume":"21","author":"C J Ruan","year":"2020","journal-title":"Pharmacogenomics"},{"key":"ref90","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1097\/FPC.0b013e3283602e75","article-title":"Pharmacogenetics of CYP1A2 activity and inducibility in smokers and exsmokers","volume":"23","author":"M Dobrinas","year":"2013","journal-title":"Pharmacogenet Genomics"},{"key":"ref91","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/acps.12673","article-title":"The significance of sampling time in therapeutic drug monitoring of clozapine","volume":"135","author":"M I Jakobsen","year":"2017","journal-title":"Acta Psychiatr Scand"},{"key":"ref92","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1097\/JCP.0000000000001341","article-title":"European Caucasians may need lower minimum therapeutic clozapine doses than those customarily proposed","volume":"41","author":"G Schoretsanitis","year":"2021","journal-title":"J Clin Psychopharmacol"},{"key":"ref93","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1097\/01.jcp.0000106221.36344.4d","article-title":"Influence of dose, cigarette smoking, age, sex, and metabolic activity on plasma clozapine concentrations: a predictive model and nomograms to aid clozapine dose adjustment and to assess compliance in individual patients","volume":"24","author":"A Rostami-Hodjegan","year":"2004","journal-title":"J Clin Psychopharmacol"},{"key":"ref94","volume-title":"La clozapine. Encyclop\u00e9die M\u00e9dico-chirurgicale","author":"C Quiles","year":"2020"},{"key":"ref96","volume-title":"Maudsley Prescribing Guidelines in Psychiatry","author":"D M Taylor","year":"2018"},{"key":"ref97","first-page":"329","article-title":"Clozapine: guidelines for clinical management","volume":"50","author":"J A Lieberman","year":"1989","journal-title":"J Clin Psychiatry"},{"key":"ref98","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1056\/NEJM199103143241107","article-title":"Clozapine. A novel antipsychotic agent","volume":"324","author":"R J Baldessarini","year":"1991","journal-title":"N Engl J Med"},{"key":"ref99","first-page":"57","article-title":"Schizophrenia life-threatening and life-saving treatment?","volume":"8","author":"L Citrome","year":"2009","journal-title":"Curr Psychiatry"},{"key":"ref100","doi-asserted-by":"crossref","first-page":"134","DOI":"10.3371\/CSRP.6.3.5","article-title":"Clozapine: balancing safety with superior antipsychotic efficacy","volume":"6","author":"H Y Meltzer","year":"2012","journal-title":"Clin Schizophr Relat Psychoses"},{"key":"ref101","first-page":"623","volume-title":"Chapter 25. Clozapine. In: Schatzberg AF, Nemeroff CB, Ed. The American Psychiatric Association Publishing textbook of psychopharmacology","author":"S R Marder","year":"2017"},{"key":"ref102","volume-title":"The clozapine handbook: Stahl\u2019s handbooks (Stahl's essential psychopharmacology handbooks)","author":"J M Meyer","year":"2020"},{"key":"ref103","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1176\/appi.psy.46.3.262","article-title":"The dosing of atypical antipsychotics","volume":"46","author":"J de Leon","year":"2005","journal-title":"Psychosomatics"},{"key":"ref104","doi-asserted-by":"crossref","first-page":"1744","DOI":"10.1176\/ajp.156.11.1744","article-title":"Double-blind study of clozapine dose response in chronic schizophrenia","volume":"156","author":"G M Simpson","year":"1999","journal-title":"Am J Psychiatry"},{"key":"ref105","doi-asserted-by":"crossref","first-page":"1307","DOI":"10.4088\/JCP.11r06977","article-title":"Beyond white blood cell monitoring: screening in the initial phase of clozapine therapy","volume":"73","author":"D Cohen","year":"2012","journal-title":"J Clin Psychiatry"},{"key":"ref106","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1177\/0004867419898760","article-title":"Systematic review and meta-analysis of rates of clozapine-associated myocarditis and cardiomyopathy","volume":"54","author":"D Siskind","year":"2020","journal-title":"Aust N Z J Psychiatry"},{"key":"ref107","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1016\/j.jocn.2015.01.016","article-title":"Lamotrigine-induced severe cutaneous adverse reaction: Update data from 1999-2014","volume":"22","author":"X Q Wang","year":"2015","journal-title":"J Clin Neurosci"},{"key":"ref108","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1111\/acps.12425","article-title":"Clozapine-induced myocarditis: prescribe safely but do prescribe","volume":"132","author":"O Freudenreich","year":"2015","journal-title":"Acta Psychiatr Scand"},{"key":"ref109","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1111\/acps.12421","article-title":"Titrating clozapine amidst recommendations proposing high myocarditis risk and rapid titrations","volume":"132","author":"J de Leon","year":"2015","journal-title":"Acta Psychiatr Scand"},{"key":"ref110","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/0920-9964(95)00047-X","article-title":"Myocarditis under therapy with clozapine","volume":"17","author":"B Bandelow","year":"1995","journal-title":"Schizophr Res"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1177\/070674370805301211","article-title":"The incidence and characteristics of clozapine- induced fever in a local psychiatric unit in Hong Kong","volume":"53","author":"J Pui-yin Chung","year":"2008","journal-title":"Can J Psychiatry"},{"key":"ref112","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1111\/acps.12241","article-title":"Effectiveness and safety of rapid clozapine titration in schizophrenia","volume":"130","author":"P Ifteni","year":"2014","journal-title":"Acta Psychiatr Scand"},{"key":"ref113","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.jad.2014.04.020","article-title":"Rapid clozapine titration in treatment-refractory bipolar disorder","volume":"166","author":"P Ifteni","year":"2014","journal-title":"J Affect Disord"},{"key":"ref114","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1177\/2045125315584871","article-title":"Effectiveness of ultra-rapid dose titration of clozapine for treatment-resistant bipolar mania: case series","volume":"5","author":"C Aksoy Poyraz","year":"2015","journal-title":"Ther Adv Psychopharmacol"},{"key":"ref115","first-page":"6457","article-title":"Risks and benefits of rapid clozapine titration","volume":"8","author":"J D Lochhead","year":"2016","journal-title":"Ment Illn"},{"key":"ref116","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1177\/0091217415621269","article-title":"Clozapine-induced myocarditis may be associated with rapid titration: A case report verified with autopsy","volume":"51","author":"N Chopra","year":"2016","journal-title":"Int J Psychiatry Med"},{"key":"ref117","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s11126-015-9394-y","article-title":"Rapid clozapine titration in patients with treatment refractory schizophrenia","volume":"87","author":"C A Poyraz","year":"2016","journal-title":"Psychiatr Q"},{"key":"ref118","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.psym.2019.08.008","article-title":"Rapid titration and decreased clozapine clearance may help explain five cases of clozapine-induced myocarditis in a New York Hospital","volume":"61","author":"J de Leon","year":"2020","journal-title":"Psychosomatics"},{"key":"ref119","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/JCP.0000000000001339","article-title":"Successful clozapine rechallenge after suspected clozapine-associated myocarditis: a case report","volume":"41","author":"M Danilewitz","year":"2021","journal-title":"J Clin Psychopharmacol"},{"key":"ref120","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.schres.2019.07.040","article-title":"Clinical determinants of fever in clozapine users and implications for treatment management: A narrative review","volume":"211","author":"H Verdoux","year":"2019","journal-title":"Schizophr Res"},{"key":"ref121","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1111\/acps.12827","article-title":"Adverse cardiac events in out-patients initiating clozapine treatment: a nationwide register-based study","volume":"137","author":"C Rohde","year":"2018","journal-title":"Acta Psychiatr Scand"},{"key":"ref122","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.rcp.2018.07.002","article-title":"High doses of drugs extensively metabolized by CYP3A4 were needed to reach therapeutic concentrations in two patients taking inducers","volume":"49","author":"N Chopra","year":"2020","journal-title":"Rev Colomb Psiquiatr"},{"key":"ref123","first-page":"CD009555","article-title":"Clozapine dose for schizophrenia","volume":"6","author":"S Subramanian","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"ref124","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1002\/cpt.690","article-title":"Worldwide distribution of Cytochrome P450 Alleles: A meta-analysis of population-scale sequencing projects","volume":"102","author":"Y Zhou","year":"2017","journal-title":"Clin Pharmacol Ther"},{"key":"ref125","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1046\/j.1365-2125.2003.01858.x","article-title":"Identification of a novel splice-site mutation in the CYP1A2 gene","volume":"56","author":"D Allorge","year":"2003","journal-title":"Br J Clin Pharmacol"},{"key":"ref126","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.dmpk.2015.03.001","article-title":"Functional characterization of 20 allelic variants of CYP1A2","volume":"30","author":"M Ito","year":"2015","journal-title":"Drug Metab Pharmacokinet"},{"key":"ref127","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2133\/dmpk.20.24","article-title":"Single nucleotide polymorphisms and haplotypes of CYP1A2 in a Japanese population","volume":"20","author":"A Soyama","year":"2005","journal-title":"Drug Metab Pharmacokinet"},{"key":"ref128","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1001\/archpsyc.55.11.1048","article-title":"Very high cytochrome P4501A2 activity and nonresponse to clozapine","volume":"55","author":"S Bender","year":"1998","journal-title":"Arch Gen Psychiatry"},{"key":"ref129","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1176\/ajp.153.12.1579","article-title":"Response of patients with treatment-refractory schizophrenia to clozapine within three serum level ranges","volume":"153","author":"C VanderZwaag","year":"1996","journal-title":"Am J Psychiatry"},{"key":"ref130","doi-asserted-by":"crossref","first-page":"607","DOI":"10.2165\/00003088-200342070-00001","article-title":"What is an adequate trial with clozapine?: therapeutic drug monitoring and time to response in treatment-refractory schizophrenia","volume":"42","author":"P Schulte","year":"2003","journal-title":"Clin 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