{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T13:43:45Z","timestamp":1786974225084,"version":"build-2736575974"},"reference-count":104,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2013,2,14]],"date-time":"2013-02-14T00:00:00Z","timestamp":1360800000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The purpose of this study was to review the scientific evidence for neurobiological rationale, efficacy, tolerability and cost effectiveness of antipsychotic polypharmacy (APP).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data sources:<\/jats:title>\n                    <jats:p>A systematic literature search of Medline, Embase, Ovid and the Cochrane Database of Systematic Reviews until April 2012 was carried out.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Theories behind APP have only modest pre-clinical and clinical evidence. We found limited statistical evidence supporting modest efficacy of APP in patients with psychotic symptoms refractory to clozapine. APP is associated with increased mortality, metabolic syndrome, decreased cognitive functioning, high dose prescription and non-adherence. It brings up extra costs, lacking evidence for cost-effectiveness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Pre-clinical studies underpinning neurobiological hypotheses in APP are lacking. Evidence supporting efficacy of APP is limited with modest beneficial clinical relevance. APP is associated with several serious adverse effects and increased health costs. In the absence of more convincing pre-clinical support and clinical evidence we advise adherence to existing guidelines and limiting combinations of antipsychotics (in consideration with other pharmacotherapeutic, somatic and psychotherapeutic options) to patients with clozapine-refractory psychosis in well-evaluated individual trials that might need 10 weeks or more.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/0269881113477709","type":"journal-article","created":{"date-parts":[[2013,2,14]],"date-time":"2013-02-14T23:02:03Z","timestamp":1360882923000},"page":"327-336","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":72,"title":["Antipsychotic polypharmacy in psychotic disorders: a critical review of neurobiology, efficacy, tolerability and cost effectiveness"],"prefix":"10.1177","volume":"27","author":[{"given":"Marc WH","family":"Lochmann van Bennekom","sequence":"first","affiliation":[{"name":"Nijmegen Early Psychosis Program, Pro Persona Mental Health Care, Aurora, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harm J","family":"Gijsman","sequence":"additional","affiliation":[{"name":"Nijmegen Early Psychosis Program, Pro Persona Mental Health Care, Aurora, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frans G","family":"Zitman","sequence":"additional","affiliation":[{"name":"Psychiatry, Leiden University Medical Centre, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2013,2,14]]},"reference":[{"key":"bibr1-0269881113477709","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1176\/appi.ajp.161.1.1","volume":"161","author":"American Psychiatric Association","year":"2004","journal-title":"Am J Psychiatry"},{"key":"bibr2-0269881113477709","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v66n0109"},{"key":"bibr3-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-993209"},{"key":"bibr4-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1007\/s10198-011-0308-0"},{"key":"bibr5-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1097\/01.yic.0000224785.68040.43"},{"key":"bibr6-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbn030"},{"key":"bibr7-0269881113477709","first-page":"209","volume":"18","author":"Barrett WW","year":"1957","journal-title":"Dis Nerv Syst"},{"key":"bibr8-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1007\/s11096-006-9063-1"},{"key":"bibr9-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.161.4.700"},{"key":"bibr10-0269881113477709","first-page":"311","volume":"16","author":"Cha C","year":"1999","journal-title":"Xinxiang Med Stud"},{"key":"bibr11-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1176\/ps.2006.57.8.1094"},{"key":"bibr12-0269881113477709","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v69n0505"},{"key":"bibr13-0269881113477709","first-page":"282","volume":"42","author":"Chen A","year":"1991","journal-title":"Hosp Community Psychiatry"},{"key":"bibr14-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.130.1.13"},{"key":"bibr15-0269881113477709","doi-asserted-by":"crossref","first-page":"457","DOI":"10.47102\/annals-acadmedsg.V35N7p457","volume":"35","author":"Chong SA","year":"2006","journal-title":"Ann Acad Med Singapore"},{"key":"bibr16-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.schbul.a033463"},{"key":"bibr17-0269881113477709","first-page":"CD006324","author":"Cipriani A","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"bibr18-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.schbul.a006928"},{"key":"bibr19-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2006.08.017"},{"key":"bibr20-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/sbn018"},{"key":"bibr21-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2011.02.016"},{"key":"bibr22-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-992133"},{"key":"bibr23-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1001\/jama.299.19.2319"},{"key":"bibr24-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0773.1990.tb01601.x"},{"key":"bibr25-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1177\/0269881108100777"},{"key":"bibr26-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2011.10060908"},{"key":"bibr27-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpsy.2008.01.784"},{"key":"bibr28-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145710000490"},{"key":"bibr29-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0447.2002.01331.x"},{"key":"bibr30-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2006.12.030"},{"key":"bibr31-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2011.14"},{"key":"bibr32-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2012.03.018"},{"key":"bibr33-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2007.09.002"},{"key":"bibr34-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1007\/BF02849987"},{"key":"bibr35-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1819.2011.02280.x"},{"key":"bibr36-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1016\/j.eurpsy.2004.07.001"},{"key":"bibr37-0269881113477709","first-page":"433","volume":"34","author":"Honer WG","year":"2009","journal-title":"J Psychiatry Neurosci"},{"key":"bibr38-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa053222"},{"key":"bibr39-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2006.05.004"},{"key":"bibr40-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.111.105833"},{"key":"bibr41-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.187.3.243"},{"key":"bibr42-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.schbul.a007117"},{"key":"bibr43-0269881113477709","first-page":"142","volume":"19","author":"Jia Z","year":"2000","journal-title":"Herald Med"},{"key":"bibr44-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.162.1.130"},{"key":"bibr45-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.158.2.311"},{"key":"bibr46-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.bp.109.076935"},{"key":"bibr47-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2010.07.029"},{"key":"bibr48-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1097\/00004850-200401000-00004"},{"key":"bibr49-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1097\/01.yic.0000188216.92408.69"},{"key":"bibr50-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1192\/pb.bp.108.024257"},{"key":"bibr51-0269881113477709","first-page":"28","volume":"14","author":"Liu Q","year":"2001","journal-title":"Shandon Arch Psychiatry"},{"key":"bibr52-0269881113477709","first-page":"87","volume":"29","author":"Liu Q","year":"1996","journal-title":"Chin J Psychiatry"},{"key":"bibr53-0269881113477709","first-page":"208","volume":"53","author":"Matthiasson P","year":"2003","journal-title":"Schizophr Res"},{"key":"bibr54-0269881113477709","volume-title":"Technical Report on Psychiatric Polypharmacy","author":"Medical Directors Council and State Medicaid Directors","year":"2001"},{"key":"bibr55-0269881113477709","first-page":"390","volume":"25","author":"Meltzer HY","year":"1989","journal-title":"Psychopharmacol Bull"},{"key":"bibr56-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1093\/schbul\/2.1.19"},{"key":"bibr57-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.schbul.a006912"},{"key":"bibr58-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1186\/1471-244X-11-118"},{"key":"bibr59-0269881113477709","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v68n1115"},{"key":"bibr60-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-977X(06)70524-7"},{"key":"bibr61-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2010.12.011"},{"key":"bibr62-0269881113477709","volume-title":"Schizophrenia. Full National Clinical Guideline on Core Interventions in Primary and Secondary Care","author":"National Institute for Clinical Excellence","year":"2009"},{"key":"bibr63-0269881113477709","first-page":"181","volume":"3","author":"Ni J","year":"2001","journal-title":"Heath Psychol J"},{"key":"bibr64-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0b013e318248dfb8"},{"key":"bibr65-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1016\/0006-3223(85)90174-X"},{"key":"bibr66-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1097\/JCP.0b013e318036bfbb"},{"key":"bibr67-0269881113477709","first-page":"100","volume":"7","author":"Peng H","year":"2001","journal-title":"J Mod Clin Med Bioeng"},{"key":"bibr68-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1007\/BF00442568"},{"key":"bibr69-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1177\/0091270009350625"},{"key":"bibr70-0269881113477709","doi-asserted-by":"publisher","DOI":"10.5414\/CPP46146"},{"key":"bibr71-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4000336"},{"key":"bibr72-0269881113477709","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v65n1203"},{"key":"bibr73-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.171.6.569"},{"key":"bibr74-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2007.06071075"},{"key":"bibr75-0269881113477709","first-page":"17","volume":"12","author":"Si S","year":"1999","journal-title":"Shandon Arch Psychiatry"},{"key":"bibr76-0269881113477709","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v60n0701"},{"key":"bibr77-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.2012.01841.x"},{"key":"bibr78-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ps.57.1.127"},{"key":"bibr79-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(96)00295-8"},{"key":"bibr80-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145703004012"},{"key":"bibr81-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.121.6.597"},{"key":"bibr82-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.2009.01367.x"},{"key":"bibr83-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0447.2011.01792.x"},{"key":"bibr84-0269881113477709","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v64n0107"},{"key":"bibr85-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60742-X"},{"key":"bibr86-0269881113477709","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-200831010-00002"},{"key":"bibr87-0269881113477709","first-page":"CD008125","author":"Wang J","year":"2010","journal-title":"Cochrane Database Syst Rev"},{"key":"bibr88-0269881113477709","first-page":"148","volume":"11","author":"Wang CH","year":"1994","journal-title":"J Xinxiang Med College"},{"key":"bibr89-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2010.101"},{"key":"bibr90-0269881113477709","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1080\/17522430903501999","volume":"2","author":"Weinmann S","year":"2010","journal-title":"Psychosis: Psychological, Social and Integrative Approaches"},{"key":"bibr91-0269881113477709","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v69n0815"},{"key":"bibr92-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1016\/j.schres.2009.05.018"},{"key":"bibr93-0269881113477709","first-page":"135","volume":"10","author":"Wu I","year":"2002","journal-title":"Heath Psychol J"},{"key":"bibr94-0269881113477709","first-page":"250","volume":"12","author":"Xao H","year":"1999","journal-title":"Sichuan Ment Health"},{"key":"bibr95-0269881113477709","first-page":"245","volume":"17","author":"Xie C","year":"2001","journal-title":"J Prev Med Inform"},{"key":"bibr96-0269881113477709","first-page":"501","volume":"20","author":"Xin X","year":"2001","journal-title":"Herald Med"},{"key":"bibr97-0269881113477709","first-page":"806","volume":"6","author":"Xu B","year":"2006","journal-title":"China Tropical Medicine"},{"key":"bibr98-0269881113477709","first-page":"351","volume":"3","author":"Yagi G","year":"1976","journal-title":"Clin Eval"},{"key":"bibr99-0269881113477709","first-page":"165","volume":"16","author":"Yue H","year":"2004","journal-title":"Shangai Arch Psychiatry"},{"key":"bibr100-0269881113477709","first-page":"306","volume":"5","author":"Zhang L","year":"1989","journal-title":"Chin J Nerv Ment Dis"},{"key":"bibr101-0269881113477709","doi-asserted-by":"publisher","DOI":"10.1186\/1471-244X-8-19"},{"key":"bibr102-0269881113477709","first-page":"15","volume":"12","author":"Zhu H","year":"2002","journal-title":"J Clin Psychol Med"},{"key":"bibr103-0269881113477709","first-page":"204","volume":"9","author":"Zhu Y","year":"1999","journal-title":"J Clin Psychol Med"},{"key":"bibr104-0269881113477709","first-page":"94","volume":"25","author":"Zou G","year":"2003","journal-title":"J Yichun Univ"}],"container-title":["Journal of Psychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0269881113477709","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0269881113477709","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0269881113477709","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:07:41Z","timestamp":1777507661000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0269881113477709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,14]]},"references-count":104,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1177\/0269881113477709"],"URL":"https:\/\/doi.org\/10.1177\/0269881113477709","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.718009500.793476550","asserted-by":"object"}]},"ISSN":["0269-8811","1461-7285"],"issn-type":[{"value":"0269-8811","type":"print"},{"value":"1461-7285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,2,14]]}}}