{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T15:19:41Z","timestamp":1773674381532,"version":"3.50.1"},"reference-count":65,"publisher":"Cambridge University Press (CUP)","issue":"15","license":[{"start":{"date-parts":[[2019,10,18]],"date-time":"2019-10-18T00:00:00Z","timestamp":1571356800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Psychol. Med."],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"S003329171900285X_sec_a1\"><jats:title>Background<\/jats:title><jats:p>Comparisons of antipsychotics with placebo can be biased by unblinding due to side effects. Therefore, this meta-analysis compared the efficacy of antipsychotics for acute schizophrenia in trials using barbiturates or benzodiazepines as active placebos.<\/jats:p><\/jats:sec><jats:sec id=\"S003329171900285X_sec_a2\" sec-type=\"methods\"><jats:title>Methods<\/jats:title><jats:p>Randomized controlled trials (RCTs) in acute schizophrenia with at least 3 weeks duration and comparing any antipsychotic with barbiturates or benzodiazepines were eligible. ClinicalTrials.gov, CENTRAL, EMBASE, MEDLINE, PsycINFO, PubMed, WHO-ICTRP as well as previous reviews were searched up to 9 January 2018. Two separate meta-analyses, one for barbiturates and one for benzodiazepines, were conducted using random-effects models. The primary outcome was response to treatment, and mean values of schizophrenia rating scales and dropouts were analyzed as secondary outcomes. This study is registered with PROSPERO (CRD42018086263).<\/jats:p><\/jats:sec><jats:sec id=\"S003329171900285X_sec_a3\" sec-type=\"results\"><jats:title>Results<\/jats:title><jats:p>Seven barbiturate-RCTs (number of participants <jats:italic>n<\/jats:italic> = 1736), and two benzodiazepine-RCTs (<jats:italic>n<\/jats:italic> = 76) were included in the analysis. The studies were published between 1960 and 1968 and involved mainly chronically ill patients. More patients on antipsychotics in comparison to barbiturates achieved a \u2018good\u2019 response (36.2% <jats:italic>v.<\/jats:italic> 16.8%; RR 2.15; 95% CI 1.36\u20133.41; <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> = 48.9) and \u2018any\u2019 response (57.4% <jats:italic>v.<\/jats:italic> 27.8%; RR 2.07; 95% CI 1.35\u20133.18; <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> = 68.2). In a single small trial (<jats:italic>n<\/jats:italic> = 60), there was no difference between antipsychotics and benzodiazepines on \u2018any\u2019 response (74.7% <jats:italic>v.<\/jats:italic> 65%; RR 1.15; 95% CI 0.82\u20131.62).<\/jats:p><\/jats:sec><jats:sec id=\"S003329171900285X_sec_a4\" sec-type=\"conclusions\"><jats:title>Conclusions<\/jats:title><jats:p>Antipsychotic drugs were more efficacious than barbiturates, based on a large sample size. Response ratios were similar to those observed in placebo-controlled trials. The results on benzodiazepines were inconclusive due to the small number of studies and participants.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s003329171900285x","type":"journal-article","created":{"date-parts":[[2019,10,18]],"date-time":"2019-10-18T11:12:46Z","timestamp":1571397166000},"page":"2622-2633","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":10,"title":["Antipsychotic drugs <i>v.<\/i> barbiturates or benzodiazepines used as active placebos for schizophrenia: a systematic review and meta-analysis"],"prefix":"10.1017","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-2039","authenticated-orcid":false,"given":"Spyridon","family":"Siafis","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomo","family":"Deste","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Ceraso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Mussoni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Vita","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Senad","family":"Hasanagic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3448-9532","authenticated-orcid":false,"given":"Johannes","family":"Schneider-Thoma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1641-9095","authenticated-orcid":false,"given":"Georgios","family":"Papazisis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John M","family":"Davis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4934-4352","authenticated-orcid":false,"given":"Stefan","family":"Leucht","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2019,10,18]]},"reference":[{"key":"S003329171900285X_ref8","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/BF00592679","article-title":"Chlorpromazine in chronic schizophrenic women: I. 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