Prescription rates of second-generation antipsychotics (SGAs) are rapidly increasing for non-indicated (i.e., off-label) usage. SGAs used for approved indications are associated with significant metabolic adverse effects, including weight gain. The objective of this systematic review and meta-analysis is to evaluate the metabolic adverse effects of SGA use for off-label management of psychiatric illnesses in the adult population. We performed a systematic database search to identify randomized controlled trials (RCTs) that reported on weight and other metabolic outcomes with off-label use of SGAs among adults. Thirty-eight RCTs met inclusion criteria for this review; 35 of these studies, with a total of 4930 patients, were included in the quantitative meta-analysis. Patients treated with olanzapine, risperidone, and quetiapine were more likely to report weight gain as a side effect and experience clinically significant (≥7%) weight gain compared to those treated with a placebo. Among studies that reported weight as a continuous outcome, olanzapine was associated with significantly greater weight gain across all disorders (mean difference (MD) = 3.24 kg, 95% CI: 2.57–3.90 p = 0.001, N = 12 studies). Similar trends were noted with quetiapine and risperidone. A meta-regression analysis revealed a positive dose-response association between olanzapine dose and weight gain (regression coefficient: 0.36, p = 0.001). This review demonstrates that off-label use of SGAs, and particularly olanzapine, is associated with significant weight gain among adult patients. Our findings are concerning given the widespread off-label use of SGAs. Further studies are required to better understand the effects of off-label SGA use on other metabolic parameters. The study was registered with the PROSPERO international database of prospectively registered systematic reviews (PROSPERO #143186).

第二代抗精神病药 (SGA) 的处方率在非指示（即标签外）使用中迅速增加。用于批准适应症的 SGA 与显着的代谢不良反应有关，包括体重增加。本系统评价和荟萃分析的目的是评估使用 SGA 对成人精神疾病的标签外管理的代谢不良影响。我们进行了系统的数据库搜索，以确定报告体重和其他代谢结果的随机对照试验 (RCT)，这些试验报告了成人在标签外使用 SGA 的情况。38 项 RCT 符合本次审查的纳入标准；其中 35 项研究，共 4930 名患者，被纳入定量荟萃分析。接受奥氮平、利培酮治疗的患者，与接受安慰剂治疗的患者相比，喹硫平更有可能将体重增加作为副作用报告，并且体重增加有临床意义（≥7%）。在将体重报告为连续结果的研究中，奥氮平与所有疾病的体重增加显着增加相关（平均差 (MD) = 3.24 kg，95% CI：2.57–3.90p  = 0.001，N  = 12 项研究）。喹硫平和利培酮也出现了类似的趋势。荟萃回归分析显示奥氮平剂量与体重增加之间呈正剂量反应关联（回归系数：0.36，p  = 0.001）。这篇综述表明，超说明书使用 SGA，尤其是奥氮平，与成年患者的体重显着增加有关。鉴于 SGA 的标签外广泛使用，我们的研究结果令人担忧。需要进一步研究以更好地了解标签外 SGA 使用对其他代谢参数的影响。该研究已在 PROSPERO 前瞻性注册系统评价国际数据库 (PROSPERO #143186) 中注册。