Background 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. Methods 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. Findings 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. Interpretation 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.

中文翻译：

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抗精神病药引起的体重增加：随机对照试验的剂量反应荟萃分析

背景 体重增加是抗精神病药最重要的副作用之一。然而，尚不清楚它是否与抗精神病药物剂量有关。我们旨在通过剂量反应荟萃分析来填补这一空白。方法 我们搜索了多个电子数据库（最后一次更新搜索时间为 2021 年 6 月），查找所有固定剂量研究，这些研究调查了 16 种第二代抗精神病药和氟哌啶醇在精神分裂症急性加重或阴性症状的成人中的作用。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。我们使用受限三次样条来模拟剂量-反应关系。主要结果是从基线到终点的平均体重增加（kg），次要结果是具有临床重要体重增加的患者人数。结果 97 项研究涉及 333 个剂量组（36 326 名受试者），为荟萃分析提供了数据。大多数研究是短期的，中位持续时间为 6 周（范围为 4 至 26 周）。在急性加重患者中，与安慰剂相比，氨磺必利、阿立哌唑、brexpiprazole、卡利拉嗪、氟哌啶醇、鲁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≤1 kg），而所有其他药物观察到更显着的体重增加. 对于大多数药物，剂量反应曲线显示初始剂量相关的体重增加在较高剂量时趋于稳定，而对于其他药物则没有稳定期，有些甚至呈钟形曲线，这意味着体重增加较少与较高剂量相关。解释 第二代抗精神病药物不仅在产生体重增加的倾向上有所不同，而且在他们的剂量反应曲线的形状。该信息对于临床实践中的剂量决定很重要。