{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:59:46Z","timestamp":1792144786276,"version":"4.4.0"},"reference-count":46,"publisher":"Georg Thieme Verlag KG","issue":"04","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacopsychiatry"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n               Background Continuous antipsychotic (AP) therapy is crucial for managing\n                    psychotic disorders, and its early interruption reflects the drug\u02bcs failure.\n                    Real-world epidemiological research is essential for confirming experimental\n                    data and generating new research hypotheses.<\/jats:p><jats:p>\n               Methods The persistence of oral APs in a large population sample from 2000\n                    to 2021 was analyzed by comparing AP prescriptions over this period across four\n                    Italian provinces, using dispensing data linked via a record-linkage procedure\n                    among regional healthcare utilization databases. We calculated personalized\n                    daily dosages and assessed time-to-treatment discontinuation over a 3-month\n                    period for patients initiating AP treatment. Treatment persistence was evaluated\n                    using Kaplan-Meier curves and Cox regression, with adjustments for age and\n                    sex.<\/jats:p><jats:p>\n               Results Second-generation antipsychotics (SGAs) were favored over\n                    first-generation antipsychotics (FGAs), with olanzapine as the most prescribed.\n                    Within the study time frame, 42,434 individuals were prescribed a new continuous\n                    AP regimen. The analysis revealed 24 significant differences within 28\n                    comparisons. As a class, SGAs demonstrated better treatment persistence than\n                    FGAs (HR: 0.76; 95%CI: 0.73, 0.79). Clozapine stood out for its superior\n                    persistence, surpassing all other SGAs, notably olanzapine (HR: 0.85; 95%CI:\n                    0.79\u20130.91) and risperidone (HR: 0.80; 95%CI: 0.74\u20130.87). Olanzapine and\n                    aripiprazole showed better results than both risperidone and quetiapine.\n                    Quetiapine showed inferior 3-month persistence in all pairwise comparisons.<\/jats:p><jats:p>\n               Conclusion The study results provide insight into the performance dynamics\n                    among SGAs: clozapine, despite being one of the less frequently dispensed APs in\n                    our sample, emerged as a significant prescription choice. The significance of\n                    pharmacoepidemiological studies in complementing experimental findings is also\n                    underscored.<\/jats:p>","DOI":"10.1055\/a-2437-4366","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T19:33:22Z","timestamp":1731353602000},"page":"159-169","source":"Crossref","is-referenced-by-count":1,"title":["2001\u20132021 Comparative Persistence of Oral Antipsychotics in Patients\n                    Initiating Treatment: Superiority of Clozapine in Time-to-Treatment\n                    Discontinuation"],"prefix":"10.1055","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2898-5134","authenticated-orcid":false,"given":"Alberto","family":"Parabiaghi","sequence":"additional","affiliation":[{"name":"Unit for Quality of Care and Rights Promotion in Mental Health,\n                    Department of Health Policy, Istituto di Ricerche Farmacologiche \u201cMario Negri\u201d \u2013\n                    IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia A.","family":"Galbussera","sequence":"additional","affiliation":[{"name":"Laboratory of Geriatric Epidemiology, Department of Health Policy,\n                    Istituto di Ricerche Farmacologiche \u201cMario Negri\u201d \u2013 IRCCS, Milan,\n                    Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"D\u2019Avanzo","sequence":"additional","affiliation":[{"name":"Laboratory for Assessing Quality of Care and Services, Department of\n                    Health Policy, Istituto di Ricerche Farmacologiche \u201cMario Negri\u201d \u2013 IRCCS, Milan,\n                    Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauro","family":"Tettamanti","sequence":"additional","affiliation":[{"name":"Laboratory of Geriatric Epidemiology, Department of Health Policy,\n                    Istituto di Ricerche Farmacologiche \u201cMario Negri\u201d \u2013 IRCCS, Milan,\n                    Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ida","family":"Fortino","sequence":"additional","affiliation":[{"name":"Directorate General for Health, Lombardy Region, Milan,\n                    Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Barbato","sequence":"additional","affiliation":[{"name":"Unit for Quality of Care and Rights Promotion in Mental Health,\n                    Department of Health Policy, Istituto di Ricerche Farmacologiche \u201cMario Negri\u201d \u2013\n                    IRCCS, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.4088\/jcp.v68n0801","article-title":"Longer time to antipsychotic treatment discontinuation for any cause is\n                    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schizophrenia: A systematic review and\n                    network meta-analysis","volume":"394","author":"M Huhn","year":"2019","journal-title":"Lancet"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1038\/mp.2011.143","article-title":"Relapse prevention in schizophrenia: A systematic review and meta-analysis of\n                    second-generation antipsychotics versus first-generation antipsychotics","volume":"18","author":"T Kishimoto","year":"2013","journal-title":"Mol Psychiatry"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1002\/wps.20632","article-title":"Long-term effectiveness of oral second-generation antipsychotics in patients\n                    with schizophrenia and related disorders: A systematic review and meta-analysis\n                    of direct head-to-head comparisons","volume":"18","author":"T Kishimoto","year":"2019","journal-title":"World 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                   latest antipsychotic drugs in schizophrenia study (CUtLASS 1)","volume":"63","author":"P B Jones","year":"2006","journal-title":"Arch Gen Psychiatry"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1093\/schbul\/sbj067","article-title":"Randomized controlled trial of effect of prescription of clozapine versus other\n                    second-generation antipsychotic drugs in resistant schizophrenia","volume":"32","author":"S W Lewis","year":"2006","journal-title":"Schizophr Bull"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.1176\/ajp.2006.163.12.2080","article-title":"Cost-effectiveness of second-generation antipsychotics and perphenazine in a\n                    randomized trial of treatment for chronic schizophrenia","volume":"163","author":"R A Rosenheck","year":"2006","journal-title":"Am J 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M Essock","year":"2011","journal-title":"Am J Psychiatry"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1111\/acps.12468","article-title":"Metabolic syndrome and drug discontinuation in schizophrenia: A randomized trial\n                    comparing aripiprazole, olanzapine, and haloperidol","volume":"133","author":"A Parabiaghi","year":"2016","journal-title":"Acta Psychiatr Scand"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1093\/ijnp\/pyaa004","article-title":"Antipsychotic treatment effectiveness in first episode of psychosis: PAFIP\n                    3-year follow-up randomized clinical trials comparing haloperidol, olanzapine,\n                    risperidone, aripiprazole, quetiapine, and ziprasidone","volume":"23","author":"M G\u00f3mez-Revuelta","year":"2020","journal-title":"Int J Neuropsychopharmacol"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1017\/S1121189X00002281","article-title":"Do findings from new trials for schizophrenia fit with existing evidence: Not\n                    duped...just beguiled?","volume":"16","author":"C E Adams","year":"2007","journal-title":"Epidemiol Psichiatr Soc"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1186\/ar1170","article-title":"Equipoise, design bias, and randomized controlled trials: The elusive ethics of\n                    new drug development","volume":"6","author":"J F Fries","year":"2004","journal-title":"Arthritis Res Ther"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1002\/14651858.MR000033.pub3","article-title":"Industry sponsorship and research outcome","author":"A Lundh","year":"2017","journal-title":"Cochrane Database Syst 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estimators","volume":"79","author":"ET R Rosenman","year":"2023","journal-title":"Biometrics"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1097\/JCP.0b013e31824a076f","article-title":"The declining use of reboxetine in years 2000 to 2006: A pharmacoepidemiological\n                    comparative study","volume":"32","author":"A Parabiaghi","year":"2012","journal-title":"J Clin Psychopharmacol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1136\/bmj.c4737","article-title":"Reboxetine for acute treatment of major depression: Systematic review and\n                    meta-analysis of published and unpublished placebo and selective serotonin\n                    reuptake inhibitor controlled trials","author":"D Eyding","year":"2010","journal-title":"BMJ"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1176\/ajp.153.8.993","article-title":"Lithium use and discontinuation in a health maintenance organization","volume":"153","author":"R E Johnson","year":"1996","journal-title":"Am J Psychiatry"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1176\/ps.2007.58.1.85","article-title":"Patterns of psychotropic drug prescription for U.S. patients with diagnoses of\n                    bipolar disorders","volume":"58","author":"R J Baldessarini","year":"2007","journal-title":"Psychiatr Serv"},{"key":"ref34"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1007\/s00228-013-1621-6","article-title":"Changes in drug prescribing to Italian community-dwelling elderly people: The\n                    EPIFARM\u2013Elderly Project 2000\u20132010","volume":"70","author":"C Franchi","year":"2014","journal-title":"Eur J Clin Pharmacol"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1136\/bmj.k3532","article-title":"The reporting of studies conducted using observational routinely collected\n                    health 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StatPearls [Internet]","author":"H A Haidary","year":"2023"},{"key":"ref46","doi-asserted-by":"publisher","first-page":"2073","DOI":"10.3390\/jcm13072073","article-title":"Association of antipsychotic polypharmacy and two-year all-cause mortality: A\n                    population-based cohort study of 33,221 Italian continuous users","volume":"13","author":"A Parabiaghi","year":"2024","journal-title":"J Clin Med"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1001\/jamapsychiatry.2017.1322","article-title":"Real-world effectiveness of antipsychotic treatments in a nationwide cohort of\n                    29,823 patients with schizophrenia","volume":"74","author":"J Tiihonen","year":"2017","journal-title":"JAMA Psychiatry"},{"key":"ref48","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/S2215-0366(23)00366-8","article-title":"Efficacy and effectiveness of antipsychotics in schizophrenia: Network\n                    meta-analyses combining evidence from randomised controlled trials and\n                    real-world data","volume":"11","author":"O Efthimiou","year":"2024","journal-title":"Lancet Psychiatry"}],"container-title":["Pharmacopsychiatry"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2437-4366.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T12:32:29Z","timestamp":1752064349000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2437-4366"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,11]]},"references-count":46,"journal-issue":{"issue":"04","published-online":{"date-parts":[[2025,7,8]]},"published-print":{"date-parts":[[2025,7]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2437-4366","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0176-3679","1439-0795"],"issn-type":[{"value":"0176-3679","type":"print"},{"value":"1439-0795","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,11]]}}}