Department of Psychiatry and Psychotherapy, School of Medicine, Technical University of Munich, Munich, Germany.
Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Schizophr Bull. 2022 May 7;48(3):643-654. doi: 10.1093/schbul/sbac001.
Weight gain is among the most important side-effects of antipsychotics. It is, however, unclear whether it is associated with antipsychotic doses. We aimed to fill this gap with a dose-response meta-analysis.
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.
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≤1 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.
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.
体重增加是抗精神病药最重要的副作用之一。然而，目前尚不清楚它是否与抗精神病药剂量有关。我们旨在通过剂量-反应荟萃分析来填补这一空白。
我们在多个电子数据库（最后更新搜索日期为 2021 年 6 月）中搜索了所有固定剂量的研究，这些研究调查了 16 种第二代抗精神病药和氟哌啶醇在急性加重期精神分裂症或阴性症状的成年人中的作用。我们通过进行随机效应剂量-反应荟萃分析来估计剂量-反应曲线。我们使用限制性立方样条来模拟剂量-反应关系。主要结局是从基线到终点的平均体重增加（kg），次要结局是有临床意义的体重增加的患者数量。
97 项研究中有 333 个剂量臂（36326 名参与者）提供了用于荟萃分析的数据。大多数研究为短期研究，中位数持续时间为 6 周（范围为 4 至 26 周）。在急性加重期患者中，与安慰剂相比，氨磺必利、阿立哌唑、布瑞哌唑、卡利培嗪、氟哌啶醇、卢美哌隆和鲁拉西酮产生轻度体重增加（任何剂量的平均差异≤1kg），而其他药物则观察到更显著的体重增加。对于大多数药物，剂量-反应曲线显示出初始剂量相关的体重增加，然后在较高剂量下趋于平稳，而对于其他药物则没有平稳期，有些甚至呈钟形曲线，这意味着较高剂量与体重减轻相关。
第二代抗精神病药不仅在引起体重增加的倾向方面存在差异，而且在其剂量-反应曲线的形状上也存在差异。这些信息对于临床实践中的剂量决策很重要。
