{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:26:09Z","timestamp":1774315569592,"version":"3.50.1"},"reference-count":70,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T00:00:00Z","timestamp":1573776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Dutch Medicines Evaluation Board"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacoepidemiology and Drug"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Run\u2010in periods are used to identify placebo\u2010responders and washout. Our aim was to assess the association of run\u2010in periods with clinical outcomes of antipsychotics in dementia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched randomized placebo\u2010controlled trials of conventional and atypical antipsychotics for neuropsychiatric symptoms (NPS) in dementia in electronic sources and references of selected articles. We extracted (a) the presence of a run\u2010in period, use of placebo\/investigated drug during run\u2010in (versus washout only), and run\u2010in duration (1 week or more) and (b) the reduction in NPS, number of participants with somnolence, extrapyramidal symptoms (EPS), and deaths per treatment group. We pooled clinical outcomes comparing antipsychotic and placebo groups in trials with and without run\u2010in.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified 35 trials. Twenty\u2010nine trials used run\u2010in. The pooled standardized mean difference in the reduction of NPS was \u22120.170 (95% CI, \u22120.227 to \u22120.112) in trials with run\u2010in and \u22120.142 (95% CI, \u22120.331 to 0.047) in trials without run\u2010in. The pooled odds ratio for somnolence was 2.8 (95% CI, 2.3\u20103.5) in trials with run\u2010in and 3.5 (95% CI, 1.2\u201010.7) in trials without run\u2010in; for EPS, these ORs were 1.8 (95% CI, 1.4\u20102.2) and 2.0 (95% CI, 1.3\u20103.1) respectively, and for mortality 1.4 (95% CI, 1.0\u20102.0) and 1.6 (95% CI, 0.7\u20103.4). The use of placebo\/investigated drug during run\u2010in and run\u2010in duration did not affect the estimates in a consistent way.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The use of run\u2010in in trials might have led to overestimated efficacy and especially underestimated risks of side effects of antipsychotics compared with placebo for NPS in dementia.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pds.4903","type":"journal-article","created":{"date-parts":[[2019,11,15]],"date-time":"2019-11-15T15:36:21Z","timestamp":1573832181000},"page":"125-133","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Run\u2010in periods and clinical outcomes of antipsychotics in dementia: A meta\u2010epidemiological study of placebo\u2010controlled trials"],"prefix":"10.1002","volume":"29","author":[{"given":"Tessa A.","family":"Hulshof","sequence":"first","affiliation":[{"name":"Department of General Practice and Elderly Care Medicine University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sytse U.","family":"Zuidema","sequence":"additional","affiliation":[{"name":"Department of General Practice and Elderly Care Medicine University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine C.","family":"Gispen\u2010de Wied","sequence":"additional","affiliation":[{"name":"Dutch Medicines Evaluation Board  Utrecht The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6865-0128","authenticated-orcid":false,"given":"Hendrika J.","family":"Luijendijk","sequence":"additional","affiliation":[{"name":"Department of General Practice and Elderly Care Medicine University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,11,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17670-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-2456(97)00118-9"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.279.3.222"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1121189X0000155X"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cct.2008.04.005"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(90)90174-Z"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.297.15.1683"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0327(89)90021-9"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.1994.63"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/da.10134"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/003151259508100264"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.jcp.0000155821.74832.f9"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/acer.12067"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2013.12030315"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780120204"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(97)00112-7"},{"key":"e_1_2_9_18_1","unstructured":"World Health Organization.WHO Collaborating Centre for Drug Statistics Methodology.http:\/\/www.whocc.no\/atc_ddd_index\/?code= N05A. 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