{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T22:17:55Z","timestamp":1792534675901,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,9,27]],"date-time":"2020-09-27T00:00:00Z","timestamp":1601164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Psychiatr Scand"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>Tobacco smoking significantly impacts clozapine blood levels and has substantial implications on individual efficacy and safety outcomes. By investigating differences in clozapine blood levels in smoking and non\u2010smoking patients on clozapine, we aim to provide guidance for clinicians how to adjust clozapine levels for patients on clozapine who change their smoking habits.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a meta\u2010analysis on clozapine blood levels, norclozapine levels, norclozapine\/clozapine ratios, and concentration to dose (C\/D) ratios in smokers and non\u2010smokers on clozapine. Data were meta\u2010analyzed using a random\u2010effects model with sensitivity analyses on dose, ethnic origin, and study quality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Data from 23 studies were included in this meta\u2010analysis with 21 investigating differences between clozapine blood levels of smokers and non\u2010smokers. In total, data from 7125 samples were included for the primary outcome (clozapine blood levels in ng\/ml) in this meta\u2010analysis. A meta\u2010analysis of all between\u2010subject studies (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a016) found that clozapine blood levels were significantly lower in smokers compared with non\u2010smokers (Standard Mean Difference (SMD) \u22120.39, 95% confidence interval (CI) \u22120.55 to \u22120.22,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.001,\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a080%). With regard to the secondary outcome, C\/D ratios (\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a016 studies) were significantly lower in the smoker group (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0645) compared with the non\u2010smoker group (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0813; SMD \u22120.70, 95%CI \u22120.84 to \u22120.56,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.00001,\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a017%).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Smoking behavior and any change in smoking behavior is associated with a substantial effect on clozapine blood levels. Reductions of clozapine dose of 30% are recommended when a patient on clozapine stops smoking. Reductions should be informed by clozapine steady\u2010state trough levels and a close clinical risk\u2010benefit evaluation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/acps.13228","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T04:02:47Z","timestamp":1598932967000},"page":"456-466","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":100,"title":["Impact of smoking behavior on clozapine blood levels \u2013 a systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"142","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7147-6167","authenticated-orcid":false,"given":"E.","family":"Wagner","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University Hospital LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"McMahon","sequence":"additional","affiliation":[{"name":"School of Medicine University of Queensland Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Falkai","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University Hospital LMU Munich Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy University Hospital LMU Munich Munich Germany"},{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics of the University Augsburg Bezirkskrankenhaus Augsburg Medical Faculty University of Augsburg Augsburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2072-9216","authenticated-orcid":false,"given":"D.","family":"Siskind","sequence":"additional","affiliation":[{"name":"School of Medicine University of Queensland Brisbane Australia"},{"name":"Metro South Addiction and Mental Health Service Brisbane Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,27]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1192\/bjp.bp.115.177261","article-title":"Clozapine v. first\u2010and second\u2010generation antipsychotics in treatment\u2010refractory schizophrenia: systematic review and meta\u2010analysis","volume":"209","author":"Siskind D","year":"2020","journal-title":"Br J Psychiat"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/acps.12700"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/2045125311405566"},{"key":"e_1_2_13_5_1","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1176\/appi.ajp.2016.16050503","article-title":"Treatment\u2010resistant schizophrenia: treatment response and resistance in psychosis (TRRIP) Working Group Consensus Guidelines on Diagnosis and Terminology","volume":"1","author":"Howes OD","year":"2017","journal-title":"Am J Psychiat"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1994.tb04385.x"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2011.04023.x"},{"key":"e_1_2_13_8_1","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.schres.2005.02.010","article-title":"A meta\u2010analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking behaviors","volume":"15","author":"Leon J","year":"2005","journal-title":"Schizophrenia Res"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-006-0209-9"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/YIC.0b013e32835ac9da"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.2009.01482.x"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-007-0288-2"},{"key":"e_1_2_13_13_1","article-title":"Do Indian patients with schizophrenia need half the recommended clozapine dose to achieve therapeutic serum level? An exploratory study","author":"Suhas S","year":"2020","journal-title":"Schizophrenia Res"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v60n0108"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.5414\/CPP41003"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hup.2223"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008571-200303000-00006"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2004.pto_940104.x"},{"key":"e_1_2_13_19_1","first-page":"1","article-title":"A Rational use of clozapine based on adverse drug reactions. Pharmacokinetics, and Clinical Pharmacopsychology","volume":"14","author":"Leon J","year":"2020","journal-title":"Psychother Psychosomat"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0000000000000899"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2009.06.005"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-010-9491-z"},{"key":"e_1_2_13_23_1","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions version 6.0 (updated July 2019)","author":"Higgins JPTTJ","year":"2011"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2019.05.033"},{"key":"e_1_2_13_25_1","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1007\/s002130000503","article-title":"Long\u2010term therapeutic drug monitoring of clozapine and metabolites in psychiatric in\u2010 and outpatients","volume":"152","author":"Dettling M","year":"2000","journal-title":"Psychopharmacology"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-1296207"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.147.11.1471"},{"key":"e_1_2_13_28_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1055\/a-1021-8827","article-title":"The effects of co\u2010prescription of pantoprazole on the clozapine metabolism","volume":"53","author":"Kuzin M","year":"2020","journal-title":"Pharmacopsychiatry"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/YIC.0b013e3283277627"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ftd.0000211801.66569.80"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v61n0809"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S163839"},{"key":"e_1_2_13_33_1","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1097\/00004714-200112000-00005","article-title":"Individual changes in clozapine levels after smoking cessation: results and a predictive model","volume":"21","author":"Meyer JM","year":"2002","journal-title":"J Clin Psychopharmacol"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0b013e318206bdcd"},{"key":"e_1_2_13_35_1","doi-asserted-by":"crossref","first-page":"3163502","DOI":"10.1155\/2019\/3163502","article-title":"Population pharmacokinetics of clozapine and norclozapine and switchability assessment between brands in uruguayan patients with schizophrenia","volume":"2019","author":"Olmos I","year":"2019","journal-title":"Biomed Res Int"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.jcp.0000106221.36344.4d"},{"key":"e_1_2_13_37_1","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":"2019","author":"Ruan C\u2010J","year":"2019","journal-title":"J Clin Psychopharmacol"},{"key":"e_1_2_13_38_1","first-page":"4","article-title":"Monitoring of plasma clozapine concentrations in patients with schizophrenia. [Spanish]","volume":"16","author":"Salazar\u2010Pereyra A","year":"2011","journal-title":"Archivos de Neurociencias"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/YIC.0000000000000250"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1999.tb02016.x"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050028"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2007.02852.x"},{"key":"e_1_2_13_43_1","first-page":"44","article-title":"Association of smoking with the therapeutic effects of the drug, side effects and plasma level of drug in patients with schizophrenia. [Chinese]","volume":"9","author":"Yue Y","year":"2005","journal-title":"Chinese J Clin Rehabilit"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-5846(01)00291-3"},{"key":"e_1_2_13_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clpt.2004.04.003"},{"key":"e_1_2_13_46_1","doi-asserted-by":"publisher","DOI":"10.2174\/1874473710801020155"},{"key":"e_1_2_13_47_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2013-004216"}],"container-title":["Acta Psychiatrica Scandinavica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acps.13228","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acps.13228","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acps.13228","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T05:10:47Z","timestamp":1693804247000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acps.13228"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,27]]},"references-count":46,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["10.1111\/acps.13228"],"URL":"https:\/\/doi.org\/10.1111\/acps.13228","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/ACPS.13228\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/ACPS.13228\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/ACPS.13228\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/ACPS.13228\/v1\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/ACPS.13228\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/ACPS.13228\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/ACPS.13228\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/ACPS.13228\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/ACPS.13228\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/ACPS.13228\/v3\/decision1","asserted-by":"object"}]},"ISSN":["0001-690X","1600-0447"],"issn-type":[{"value":"0001-690X","type":"print"},{"value":"1600-0447","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,27]]},"assertion":[{"value":"2020-06-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}