Schizophrenia Division, Centre for Addiction and Mental Health (CAMH), Toronto, Canada.
Institute of Medical Sciences, University of Toronto, Toronto, Canada.
Neuropsychopharmacology. 2022 Feb;47(3):664-672. doi: 10.1038/s41386-021-01163-7. Epub 2021 Aug 26.
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).
第二代抗精神病药物（SGAs）的处方率正在迅速上升，用于非适应症（即标签外）用途。用于批准适应症的 SGAs 与显著的代谢不良影响有关，包括体重增加。本系统评价和荟萃分析的目的是评估 SGA 用于成人精神疾病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 SGAs 标签外使用与成人体重和其他代谢结果相关的随机对照试验（RCT）。38 项 RCT 符合本综述的纳入标准；其中 35 项研究，共 4930 名患者，纳入定量荟萃分析。与安慰剂相比，接受奥氮平、利培酮和喹硫平治疗的患者更有可能报告体重增加作为副作用，并经历临床显著（≥7%）的体重增加。在报告体重为连续结局的研究中，奥氮平与所有疾病的体重增加显著相关（平均差异（MD）=3.24kg，95%CI：2.57-3.90，p=0.001，N=12 项研究）。喹硫平和利培酮也有类似的趋势。荟萃回归分析显示奥氮平剂量与体重增加之间存在正剂量反应关系（回归系数：0.36，p=0.001）。本综述表明，SGAs 的标签外使用，特别是奥氮平，与成年患者的显著体重增加有关。鉴于 SGAs 的广泛标签外使用，我们的发现令人担忧。需要进一步的研究来更好地了解 SGAs 标签外使用对其他代谢参数的影响。该研究在 PROSPERO 国际前瞻性注册系统评价数据库（PROSPERO #143186）中进行了注册。
