<b><i>Background:</i></b> Serious mental illness (SMI) reduces life expectancy, primarily due to somatic comorbidity linked to obesity. Meta-analyses have found beneficial effects of lifestyle interventions in people with SMI and recommended their implementation to manage obesity. <b><i>Objective:</i></b> The objective of this systematic review was to assess the benefits and harms of individualized lifestyle interventions for weight in people diagnosed with SMI and to explore potential mediators and moderators of the effect. <b><i>Methods:</i></b> The protocol was registered at PROSPERO (CRD42016049093). Randomized clinical trials (RCTs) assessing the effect of individualized lifestyle interventions on weight management in people with SMI were included. Primary outcomes were differences in endpoint body mass index (BMI) and the proportion achieving clinically relevant weight loss (≥5%). Secondary outcomes included quality of life, cardiometabolic risk factors, and adverse effects. <b><i>Results:</i></b> We included 41 RCTs (<i>n</i> = 4,267). All trials were at high risk of bias according to the Cochrane Handbook for Systematic Reviews of Interventions. The experimental interventions reduced the mean difference in BMI by –0.63 kg/m² (95% confidence interval [CI] = –1.02 to –0.23; <i>p</i> = 0.002; <i>I</i>² = 70.7%) compared to the control groups. At postintervention follow-up (17 RCTs), the effect size remained similar but was no longer significant (BMI = –0.63 kg/m²; 95% CI = –1.30 to 0.04; <i>p</i> = 0.07; <i>I</i>² = 48.8%). The risk ratio for losing ≥5% of baseline weight was 1.51 (95% CI = 1.07–2.13; <i>p</i> = 0.02) compared to the control groups. GRADE showed very low or low quality of evidence. <b><i>Conclusion:</i></b> There is a statistically significant, but clinically insignificant, mean effect of individualized lifestyle interventions for weight reduction in people with SMI.

Background and AimsWeight gain is a major adverse effect of antipsychotic medication, negatively affecting physical and mental well-being. The objective of this study was to explore if dose reduction, discontinuation, switch to a partial agonist, or switch from polypharmacy to monotherapy will lead to weight loss.MethodsControlled and uncontrolled studies reporting the effects of discontinuation, dose reduction, switch to a partial agonist, or switch from polypharmacy to monotherapy on weight were included. Primary outcome was difference in weight compared to maintenance groups based on controlled studies. Secondary outcome was change in weight from initiation of one of the included interventions until follow-up in a pre-post analysis.ResultsWe identified 40 randomized controlled trials and 15 uncontrolled studies including 12,279 individuals. The effect of the interventions, i.e. dose reduction, drug discontinuation, or switch to a partial agonis, reduced the weight with 1.5 kg (95% CI −2.03 to −0.98; P &lt; 0.001) compared to maintenance treatment. The weight change from pre to post was a reduction of 1.13 kg (95% CI −1.36 to −0.90; P &lt; 0.001).ConclusionWe found a significant but small reduction in weight, suggesting that antipsychotic-induced weight gain can be reversed to some degree. Only a few studies were designed to address the question as primary outcome, which limits the generalizability of our findings.