{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:59:58Z","timestamp":1788969598963,"version":"build-2803163510"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T00:00:00Z","timestamp":1715040000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Australian National Health and Medical Research Council","award":["APP1138514"],"award-info":[{"award-number":["APP1138514"]}]},{"name":"Australian National Health"},{"name":"Medical Research Council Investigator","award":["APP1194635"],"award-info":[{"award-number":["APP1194635"]}]},{"name":"Medical Research Council Investigator","award":["APP1172917"],"award-info":[{"award-number":["APP1172917"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background and Hypothesis<\/jats:title>\n                  <jats:p>The ClozaGene Study is a nationwide cohort of adults who have been treated with clozapine. While clozapine is indicated in the management of treatment-resistant schizophrenia, it is associated with a considerable adverse drug reaction (ADR) burden, and not all patients achieve adequate symptomatic response. The current study focuses on self-reported experiences of clozapine use and response, clozapine-associated ADRs, and mental health comorbidity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Study Design<\/jats:title>\n                  <jats:p>A total of 1021 participants (41.0% female; aged 46.2\u2005\u00b1\u200510.6 years [range 18\u201366]) were recruited via a mail-out based on prescriptions for clozapine. Participants completed a self-report questionnaire.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Study Results<\/jats:title>\n                  <jats:p>Most participants (90.1%, n\u2005=\u2005912) were living with schizophrenia while 41.5% reported a lifetime diagnosis of depression, 15.6% bipolar disorder, and 8.1% schizoaffective disorder. Clozapine was currently prescribed to 944 (92.5%) participants and 37.8% of these participants self-reported currently taking additional antipsychotic medication. Nearly 3 quarters of participants living with schizophrenia reported that clozapine helped control their schizophrenia symptoms moderately to very well. The most commonly reported ADRs were sialorrhea (80.3%), weight gain (71.0%), constipation (56.9%), and sedation (52.8%). The prevalence of clozapine cessation due to clozapine-induced myocarditis and neutropenia was 1% and 0.4%, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our findings highlight the high rate of psychotic and metabolic symptoms and ADRs among adults prescribed clozapine in the general Australian population. Future genomic analyses will focus on identifying genetic variants influencing clozapine treatment response and side effects.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/schbul\/sbae065","type":"journal-article","created":{"date-parts":[[2024,5,7]],"date-time":"2024-05-07T14:08:14Z","timestamp":1715090894000},"page":"458-469","source":"Crossref","is-referenced-by-count":14,"title":["Clozapine Efficacy and Adverse Drug Reactions Among a Nationwide Study of 1021 Australians Prescribed Clozapine: The ClozaGene Study"],"prefix":"10.1093","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3887-2598","authenticated-orcid":false,"given":"Penelope A","family":"Lind","sequence":"first","affiliation":[{"name":"Psychiatric Genetics, Mental Health and Neuroscience Research Program, QIMR Berghofer Medical Research Institute , Brisbane ,","place":["Australia"]},{"name":"School of Biomedical Sciences, Queensland University of Technology , Brisbane ,","place":["Australia"]},{"name":"School of Biomedical Sciences, University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard K","family":"Parker","sequence":"additional","affiliation":[{"name":"Psychiatric Genetics, Mental Health and Neuroscience Research Program, QIMR Berghofer Medical Research Institute , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korinne","family":"Northwood","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Queensland , Brisbane ,","place":["Australia"]},{"name":"Metro South Addiction and Mental Health Service , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2072-9216","authenticated-orcid":false,"given":"Dan J","family":"Siskind","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Queensland , Brisbane ,","place":["Australia"]},{"name":"Metro South Addiction and Mental Health Service , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah E","family":"Medland","sequence":"additional","affiliation":[{"name":"Psychiatric Genetics, Mental Health and Neuroscience Research Program, QIMR Berghofer Medical Research Institute , Brisbane ,","place":["Australia"]},{"name":"School of Psychology and Counselling, Queensland University of Technology , Brisbane ,","place":["Australia"]},{"name":"School of Psychology, University of Queensland , Brisbane ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,7]]},"reference":[{"issue":"3","key":"2025031503070099000_CIT0001","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1192\/bjp.2021.61","article-title":"Rates of treatment-resistant schizophrenia from first-episode cohorts: systematic review and meta-analysis","volume":"220","author":"Siskind","year":"2022","journal-title":"Br J Psychiatry."},{"issue":"3","key":"2025031503070099000_CIT0002","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1176\/appi.ajp.2016.16050503","article-title":"Treatment-resistant schizophrenia: treatment response and resistance in psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology","volume":"174","author":"Howes","year":"2017","journal-title":"Am J Psychiatry."},{"issue":"5","key":"2025031503070099000_CIT0003","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1192\/bjp.bp.115.177261","article-title":"Clozapine v. first-and second-generation antipsychotics in treatment-refractory schizophrenia: systematic review and meta-analysis","volume":"209","author":"Siskind","year":"2016","journal-title":"Br J Psychiatry."},{"issue":"2","key":"2025031503070099000_CIT0004","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1093\/schbul\/sby052","article-title":"Clozapine and long-term mortality risk in patients with schizophrenia: a systematic review and meta-analysis of studies lasting 1.1\u201312.5 years","volume":"45","author":"Vermeulen","year":"2019","journal-title":"Schizophr Bull."},{"issue":"4","key":"2025031503070099000_CIT0005","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1093\/schbul\/sbad030","article-title":"Clozapine optimization: a delphi consensus guideline from the treatment response and resistance in psychosis working group","volume":"49","author":"Wagner","year":"2023","journal-title":"Schizophr Bull."},{"issue":"2","key":"2025031503070099000_CIT0006","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1111\/acps.12898","article-title":"Meta-analysis examining the epidemiology of clozapine-associated neutropenia","volume":"138","author":"Myles","year":"2018","journal-title":"Acta Psychiatr Scand."},{"issue":"1","key":"2025031503070099000_CIT0007","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/S2215-0366(23)00343-7","article-title":"Evaluating the epidemiology of clozapine-associated neutropenia among people on clozapine across Australia and Aotearoa New Zealand: a retrospective cohort study","volume":"11","author":"Northwood","year":"2024","journal-title":"Lancet Psychiatry"},{"issue":"5","key":"2025031503070099000_CIT0008","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":"Siskind","year":"2020","journal-title":"Aust N Z J Psychiatry."},{"key":"2025031503070099000_CIT0009","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.ebiom.2016.02.020","article-title":"Clozapine-treated patients have marked gastrointestinal hypomotility, the probable basis of life-threatening gastrointestinal complications: a cross sectional study","volume":"5","author":"Every-Palmer","year":"2016","journal-title":"EBioMedicine"},{"issue":"5","key":"2025031503070099000_CIT0010","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1097\/JCP.0000000000001432","article-title":"The effect of clozapine on self-reported duration of sleep and its interaction with 23 other medications: a 5-year naturalistic study","volume":"41","author":"Fernandez-Egea","year":"2021","journal-title":"J Clin Psychopharmacol."},{"issue":"9","key":"2025031503070099000_CIT0011","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.4088\/JCP.v66n0905","article-title":"Clozapine, diabetes mellitus, hyperlipidemia, and cardiovascular risks and mortality: results of a 10-year naturalistic study","volume":"66","author":"Henderson","year":"2005","journal-title":"J Clin Psychiatry."},{"key":"2025031503070099000_CIT0012","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1007\/s40263-019-00612-8","article-title":"Treatment strategies for clozapine-induced sialorrhea: a systematic review and meta-analysis","volume":"33","author":"Chen","year":"2019","journal-title":"CNS Drugs"},{"issue":"12","key":"2025031503070099000_CIT0013","doi-asserted-by":"publisher","first-page":"e0243437","DOI":"10.1371\/journal.pone.0243437","article-title":"The side effect profile of Clozapine in real world data of three large mental health hospitals","volume":"15","author":"Iqbal","year":"2020","journal-title":"PLoS One."},{"key":"2025031503070099000_CIT0014","doi-asserted-by":"publisher","first-page":"100188","DOI":"10.1016\/j.eclinm.2019.10.001","article-title":"Reported adverse drug reactions in women and men: aggregated evidence from globally collected individual case reports during half a century","volume":"17","author":"Watson","year":"2019","journal-title":"EClinicalMedicine"},{"issue":"11","key":"2025031503070099000_CIT0015","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1177\/0706743717718167","article-title":"Clozapine response rates among people with treatment-resistant schizophrenia: data from a systematic review and meta-analysis","volume":"62","author":"Siskind","year":"2017","journal-title":"Can J Psychiatry"},{"issue":"9","key":"2025031503070099000_CIT0016","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1001\/archpsyc.1988.01800330013001","article-title":"Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine","volume":"45","author":"Kane","year":"1988","journal-title":"Arch Gen Psychiatry."},{"issue":"5","key":"2025031503070099000_CIT0017","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1080\/08039488.2020.1857832","article-title":"Attitude towards and experience with clozapine of patients and their caregivers after three months of starting of clozapine","volume":"75","author":"Verma","year":"2021","journal-title":"Nord J Psychiatry."},{"issue":"12","key":"2025031503070099000_CIT0018","doi-asserted-by":"publisher","first-page":"450","DOI":"10.1192\/pb.24.12.450","article-title":"Clozapine\u2014a survey of patient perceptions","volume":"24","author":"Taylor","year":"2018","journal-title":"Psychiatr Bull"},{"issue":"11","key":"2025031503070099000_CIT0019","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.4103\/indianjpsychiatry.indianjpsychiatry_585_23","article-title":"Experience with and attitude toward clozapine use among patients receiving clozapine on long term and their caregivers","volume":"65","author":"Grover","year":"2023","journal-title":"Indian J Psychiatry"},{"issue":"1","key":"2025031503070099000_CIT0020","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1038\/s41398-020-0722-0","article-title":"Genetic associations with clozapine-induced myocarditis in patients with schizophrenia","volume":"10","author":"Lacaze","year":"2020","journal-title":"Transl Psychiatry."},{"issue":"1","key":"2025031503070099000_CIT0021","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/s41398-021-01470-z","article-title":"Genetic risk of clozapine-induced leukopenia and neutropenia: a genome-wide association study","volume":"11","author":"Chen","year":"2021","journal-title":"Transl Psychiatry."},{"issue":"1","key":"2025031503070099000_CIT0022","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1038\/mp.2017.214","article-title":"Genome-wide common and rare variant analysis provides novel insights into clozapine-associated neutropenia","volume":"23","author":"Legge","year":"2018","journal-title":"Mol Psychiatry."},{"key":"2025031503070099000_CIT0023","doi-asserted-by":"publisher","first-page":"4757","DOI":"10.1038\/ncomms5757","article-title":"Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles","volume":"5","author":"Goldstein","year":"2014","journal-title":"Nat Commun."},{"issue":"5","key":"2025031503070099000_CIT0024","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1097\/YPG.0000000000000320","article-title":"Genetic determinants associated with response to clozapine in schizophrenia: an umbrella review","volume":"32","author":"van der Horst","year":"2022","journal-title":"Psychiatr Genet."},{"issue":"1\u20132","key":"2025031503070099000_CIT0025","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1016\/j.schres.2015.07.052","article-title":"Glasgow antipsychotic side-effects scale for clozapine\u2014development and validation of a clozapine-specific side-effects scale","volume":"168","author":"Hynes","year":"2015","journal-title":"Schizophr Res."},{"key":"2025031503070099000_CIT0026","author":"New Zealand Medicines and Medical Devices Safety Authority"},{"issue":"2","key":"2025031503070099000_CIT0027","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1111\/sjop.12683","article-title":"Mapping psychotic-like experiences: results from an online survey","volume":"62","author":"Kusztrits","year":"2021","journal-title":"Scand J Psychol."},{"key":"2025031503070099000_CIT0028","author":"Australian Government Department of Health","year":"2021","journal-title":"Modified Monash Model"},{"key":"2025031503070099000_CIT0029","author":"Australian Bureau of Statistics","year":"2021"},{"key":"2025031503070099000_CIT0030","author":"Australian Bureau of Statistics","year":"2022"},{"key":"2025031503070099000_CIT0031","author":"World Health Organization"},{"issue":"3","key":"2025031503070099000_CIT0032","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1017\/S2045796016000305","article-title":"Clozapine users in Australia: their characteristics and experiences of care based on data from the 2010 National Survey of High Impact Psychosis","volume":"26","author":"Siskind","year":"2017","journal-title":"Epidemiol Psychiatr Sci"},{"issue":"8","key":"2025031503070099000_CIT0033","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1177\/0004867412449877","article-title":"People living with psychotic illness in 2010: the second Australian national survey of psychosis","volume":"46","author":"Morgan","year":"2012","journal-title":"Aust N Z J Psychiatry."},{"key":"2025031503070099000_CIT0034","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.2147\/PPA.S366522","article-title":"Understanding the treatment preferences of people living with schizophrenia in Australia; A Patient Value Mapping Study","volume":"16","author":"Fifer","year":"2022","journal-title":"Patient Prefer Adherence"},{"issue":"4\u20135","key":"2025031503070099000_CIT0035","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1055\/s-0035-1554713","article-title":"Increasing clozapine dispensing trends in Queensland, Australia 2004-2013","volume":"48","author":"Forrester","year":"2015","journal-title":"Pharmacopsychiatry."},{"issue":"2","key":"2025031503070099000_CIT0036","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1192\/pb.30.2.55","article-title":"Off-label prescribing by psychiatrists","volume":"30","author":"Hodgson","year":"2006","journal-title":"Psychiatr Bull"},{"issue":"5","key":"2025031503070099000_CIT0037","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1192\/bjb.2018.64","article-title":"Maintenance doses for clozapine: past and present","volume":"42","author":"Sharma","year":"2018","journal-title":"BJPsych Bull"},{"key":"2025031503070099000_CIT0038","doi-asserted-by":"publisher","first-page":"115539","DOI":"10.1016\/j.psychres.2023.115539","article-title":"Comprehensive dissection of prevalence rates, sex differences, and blood level-dependencies of clozapine-associated adverse drug reactions","volume":"330","author":"van der Horst","year":"2023","journal-title":"Psychiatry Res."},{"issue":"3","key":"2025031503070099000_CIT0039","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1080\/08039488.2021.1942981","article-title":"Antipsychotic drug use in Greenland and Denmark: longitudinal and cross-sectional data","volume":"76","author":"Alberdi","year":"2022","journal-title":"Nord J Psychiatry."},{"key":"2025031503070099000_CIT0040","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.schres.2020.03.032","article-title":"Constipation screening in people taking clozapine: a diagnostic accuracy study","volume":"220","author":"Every-Palmer","year":"2020","journal-title":"Schizophr Res."},{"issue":"4","key":"2025031503070099000_CIT0041","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1097\/YIC.0b013e32819f8f17","article-title":"Prevalence and nature of side effects during clozapine maintenance treatment and the relationship with clozapine dose and plasma concentration","volume":"22","author":"Yusufi","year":"2007","journal-title":"Int Clin Psychopharmacol."},{"issue":"7","key":"2025031503070099000_CIT0042","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.3390\/biom11071030","article-title":"Clozapine: why is it so uniquely effective in the treatment of a range of neuropsychiatric disorders","volume":"11","author":"Gammon","year":"2021","journal-title":"Biomolecules"},{"issue":"8","key":"2025031503070099000_CIT0043","doi-asserted-by":"publisher","first-page":"339","DOI":"10.4140\/TCP.n.2022.339","article-title":"Management of Parkinson\u2019s disease psychosis","volume":"37","author":"Elsibai","year":"2022","journal-title":"Sr Care Pharm."}],"container-title":["Schizophrenia Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/schizophreniabulletin\/article-pdf\/51\/2\/458\/57437037\/sbae065.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/schizophreniabulletin\/article-pdf\/51\/2\/458\/57437037\/sbae065.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,15]],"date-time":"2025-03-15T03:07:17Z","timestamp":1742008037000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/schizophreniabulletin\/article\/51\/2\/458\/7666232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,7]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2024,5,7]]},"published-print":{"date-parts":[[2025,3,14]]}},"URL":"https:\/\/doi.org\/10.1093\/schbul\/sbae065","relation":{},"ISSN":["0586-7614","1745-1701"],"issn-type":[{"value":"0586-7614","type":"print"},{"value":"1745-1701","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,3]]},"published":{"date-parts":[[2024,5,7]]}}}