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We aimed to fill this gap with a dose-response meta-analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We searched multiple electronic databases (last update search June 2021) for all fixed-dose studies that investigated 16 second-generation antipsychotics and haloperidol in adults with acute exacerbation of schizophrenia or with negative symptoms. We estimated the dose-response curves by conducting random-effects dose-response meta-analyses. We used the restricted cubic spline to model the dose-response relationship. The primary outcome was mean weight gain in kg from baseline to endpoint, the secondary outcome was the number of patients with clinically important weight gain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Findings<\/jats:title><jats:p>Ninety-seven studies with 333 dose arms (36 326 participants) provided data for meta-analyses. Most studies were short-term with median duration of 6 weeks (range 4 to 26 weeks). In patients with acute exacerbation, amisulpride, aripiprazole, brexpiprazole, cariprazine, haloperidol, lumateperone, and lurasidone produced mild weight gain in comparison to placebo (mean difference at any dose\u22641 kg), while more significant weight gain was observed by all other drugs. For most drugs, dose-response curves showed an initial dose-related increase in weight which plateaued at higher doses, while for others there was no plateau and some even had bell-shaped curves, meaning less weight gain to be associated with higher doses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Second-generation antipsychotics do not only differ in their propensity to produce weight gain, but also in the shapes of their dose-response curves. This information is important for dosing decisions in clinical practice.<\/jats:p><\/jats:sec>","DOI":"10.1093\/schbul\/sbac001","type":"journal-article","created":{"date-parts":[[2022,1,5]],"date-time":"2022-01-05T12:10:55Z","timestamp":1641384655000},"page":"643-654","source":"Crossref","is-referenced-by-count":124,"title":["Antipsychotic-Induced Weight Gain: Dose-Response Meta-Analysis of Randomized Controlled Trials"],"prefix":"10.1093","volume":"48","author":[{"given":"Hui","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, Munich, Germany"},{"name":"Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyridon","family":"Siafis","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, School 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3830-8508","authenticated-orcid":false,"given":"Georgia","family":"Salanti","sequence":"additional","affiliation":[{"name":"Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4934-4352","authenticated-orcid":false,"given":"Stefan","family":"Leucht","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, Munich, Germany"},{"name":"Institute of Psychiatry, Psychology and Neuroscience, Department of Psychiatry, Department of Psychosis Studies, King\u2019s College London, London, 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