{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:48:51Z","timestamp":1791600531549,"version":"4.3.4"},"reference-count":24,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: People with schizophrenia may experience altered cancer risk because of lifestyle-, healthcare access-, and treatment-related factors. Evidence on the solid cancer risk associated with clozapine remains limited. We aimed to assess solid cancer incidence among clozapine users in Lithuania between 2013 and 2021. Methods: We conducted a retrospective population-based cohort study linking National Health Insurance Fund records with the Lithuanian Cancer Registry. Patients with schizophrenia treated with clozapine during 2013\u20132021 were followed from the first recorded clozapine prescription until death, emigration, or 31 December 2021. Standardized incidence ratios (SIR) for cancers were calculated as the ratio of observed cancer cases in the clozapine user cohort to the expected number of cancers in the general Lithuanian population. Results: The cohort included 3473 clozapine users and 91 incident cancers. Overall cancer incidence was lower than expected in males. Among men with at least 3 years of clozapine exposure, prostate cancer incidence was reduced (SIR 0.47, 95% CI 0.22\u20130.98). Among women with at least 3 years of exposure, corpus uteri cancer incidence was increased (SIR 2.42, 95% CI 1.21\u20134.83). Conclusions: Current evidence on solid cancer incidence among clozapine users remains limited. Prolonged exposure may be associated with cancer-specific rather than uniform changes in risk. These exploratory findings should be interpreted cautiously and support continued attention to cancer surveillance and further large-scale pharmacoepidemiological studies with longer follow-up.<\/jats:p>","DOI":"10.3390\/jcm15197739","type":"journal-article","created":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:40:17Z","timestamp":1791596417000},"page":"7739","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clozapine and Solid Cancer Risk in Lithuania: A Population-Based Cohort Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Mingaile","family":"Drevinskaite","sequence":"first","affiliation":[{"name":"Laboratory of Cancer Epidemiology, National Cancer Institute, 08406 Vilnius, Lithuania"},{"name":"Department of Public Health, Institute of Health Sciences, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Arunas","family":"Germanavicius","sequence":"additional","affiliation":[{"name":"Clinic of Psychiatry, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania"},{"name":"Republican Vilnius Psychiatric Hospital, 11205 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8365-543X","authenticated-orcid":false,"given":"Giedre","family":"Smailyte","sequence":"additional","affiliation":[{"name":"Laboratory of Cancer Epidemiology, National Cancer Institute, 08406 Vilnius, Lithuania"},{"name":"Department of Public Health, Institute of Health Sciences, Faculty of Medicine, Vilnius University, 03101 Vilnius, Lithuania"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"ref_1","unstructured":"(2026, June 29). What Is Serious Mental Illness?. Available online: https:\/\/www.psychiatry.org:443\/patients-families\/what-is-serious-mental-illness."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.24869\/psyd.2017.108","article-title":"Causes of mortality in schizophrenia: An updated review of European studies","volume":"29","author":"Piotrowski","year":"2017","journal-title":"Psychiatr. Danub."},{"key":"ref_3","unstructured":"Hany, M., Rehman, B., Rizvi, A., and Chapman, J. (2025). Schizophrenia. StatPearls, StatPearls Publishing. Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK539864\/."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1176\/appi.ajp.20240738","article-title":"Antipsychotic Drugs: A Concise Review of History, Classification, Indications, Mechanism, Efficacy, Side Effects, Dosing, and Clinical Application","volume":"181","author":"Leucht","year":"2024","journal-title":"Am. J. Psychiatry"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1177\/1359786810385489","article-title":"Cancer and schizophrenia: Is there a paradox?","volume":"24","author":"Hodgson","year":"2010","journal-title":"J. Psychopharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.drugalcdep.2018.07.011","article-title":"Prevalence of comorbid substance use in schizophrenia spectrum disorders in community and clinical settings, 1990-2017: Systematic review and meta-analysis","volume":"191","author":"Hunt","year":"2018","journal-title":"Drug Alcohol Depend."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1192\/S0007125000297080","article-title":"Cancer incidence of schizophrenic patients. Results of record linkage studies in three countries","volume":"161","author":"Gulbinat","year":"1992","journal-title":"Br. J. Psychiatry Suppl."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/S0022-3565(25)10322-4","article-title":"Tamoxifen-resistant human breast cancer cell growth: Inhibition by thioridazine, pimozide and the calmodulin antagonist, W-13","volume":"263","author":"Strobl","year":"1992","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1192\/bjp.2024.170","article-title":"Breast cancer risk among women with schizophrenia and association with duration of antipsychotic use: Population-based cohort study in South Korea","volume":"226","author":"Yang","year":"2025","journal-title":"Br. J. Psychiatry"},{"key":"ref_10","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."},{"key":"ref_11","unstructured":"Haidary, H.A., and Padhy, R.K. (2025). Clozapine. StatPearls, StatPearls Publishing. Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK535399\/."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1517\/14740338.4.4.731","article-title":"A review of clozapine safety","volume":"4","author":"Fitzsimons","year":"2005","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/S2215-0366(22)00044-X","article-title":"Long-term treatment with clozapine and other antipsychotic drugs and the risk of haematological malignancies in people with schizophrenia: A nationwide case-control and cohort study in Finland","volume":"9","author":"Tiihonen","year":"2022","journal-title":"Lancet Psychiatry"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"dyaf118","DOI":"10.1093\/ije\/dyaf118","article-title":"Data Resource Profile: The Lithuanian health data reuse pathway","volume":"54","author":"Juodakis","year":"2025","journal-title":"Int. J. Epidemiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3231","DOI":"10.1017\/S0033291716002014","article-title":"Two distinct patterns of treatment resistance: Clinical predictors of treatment resistance in first-episode schizophrenia spectrum psychoses","volume":"46","author":"Lally","year":"2016","journal-title":"Psychol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1192\/bjb.2018.67","article-title":"Barriers to using clozapine in treatment-resistant schizophrenia: Systematic review","volume":"43","author":"Farooq","year":"2019","journal-title":"BJPsych Bull."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"17984","DOI":"10.1038\/s41598-020-75022-8","article-title":"Temporal trends in clozapine use at time of discharge among people with schizophrenia at two public psychiatric hospitals in Taiwan, 2006\u20132017","volume":"10","author":"Lin","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/acps.12742","article-title":"International trends in clozapine use: A study in 17 countries","volume":"136","author":"Bachmann","year":"2017","journal-title":"Acta Psychiatr. Scand."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s40801-024-00417-2","article-title":"Relationship Between Clozapine and Non-Hematological Malignant Tumors: A Pharmacovigilance Analysis Using the FDA Adverse Event Reporting System Database","volume":"11","author":"Uwai","year":"2024","journal-title":"Drugs Real World Outcomes"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Saed, L., Varse, F., Baradaran, H.R., Moradi, Y., Khateri, S., Friberg, E., Khazaei, Z., Gharahjeh, S., Tehrani, S., and Sioofy-Khojine, A.B. (2019). The effect of diabetes on the risk of endometrial Cancer: An updated a systematic review and meta-analysis. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-5748-4"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1038\/sj.bjc.6603259","article-title":"Cancer risk among users of neuroleptic medication: A population-based cohort study","volume":"95","author":"Dalton","year":"2006","journal-title":"Br. J. Cancer"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1016\/S2215-0366(21)00241-8","article-title":"Antipsychotic use and risk of breast cancer in women with schizophrenia: A nationwide nested case-control study in Finland","volume":"8","author":"Taipale","year":"2021","journal-title":"Lancet Psychiatry"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"4484","DOI":"10.1002\/cam4.2329","article-title":"Antipsychotic use is inversely associated with gastric cancer risk: A nationwide population-based nested case-control study","volume":"8","author":"Hsieh","year":"2019","journal-title":"Cancer Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1007\/s12272-018-1017-3","article-title":"Antipsychotic dopamine receptor antagonists, cancer, and cancer stem cells","volume":"41","author":"Roney","year":"2018","journal-title":"Arch. Pharm. Res."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/19\/7739\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T01:55:08Z","timestamp":1791597308000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/19\/7739"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,8]]},"references-count":24,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["jcm15197739"],"URL":"https:\/\/doi.org\/10.3390\/jcm15197739","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,8]]}}}