School of Pharmacy, University College London, London, UK.
College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia.
Paediatr Drugs. 2019 Jun;21(3):153-167. doi: 10.1007/s40272-019-00333-x.
Antipsychotic medication is a commonly prescribed drug class in individuals with autism spectrum disorder (ASD). However, the safety of these agents has not been fully assessed.
Our objective was to investigate the safety and tolerability profile of antipsychotics in individuals with ASD.
The Cochrane Library, MEDLINE, Embase and PsycINFO databases were searched up to January 2018. We included studies that reported adverse events (AEs) in participants with ASD taking first- or second-generation antipsychotic medication. The studies included in the analysis were randomized controlled trials (RCTs) and observational studies that were comparative or noncomparative and published as full text in the English language. The primary outcome of this review was AEs of any severity reported with antipsychotic use at any dose. Meta-analysis was performed on studies with child and adolescent participants to estimate the pooled prevalence of the overall AEs and the relative risk (RR) of AEs associated with antipsychotic use using a random-effects model. The Cochrane Collaboration tool and the modified Newcastle-Ottawa Scale (NOS) were used to assess the risk of bias of the included RCTs and observational studies, respectively.
In total, 54 citations fulfilled the inclusion criteria, of which 40 were RCTs and 14 were observational studies; eight RCTs were included in the meta-analysis to estimate the RR of AEs associated with antipsychotic use and seven observational studies were included to estimate the pooled prevalence of AEs. The RR of AEs with antipsychotic treatment was 22% higher than with placebo (RR 1.22; 95% confidence interval [CI] 1.11-1.34; I = 30.6%; p = 0.184). The estimated pooled prevalence of AEs was 50.5% (95% CI 33-67). The most commonly reported AEs were increased appetite and weight gain, which were associated with discontinuation in many participants.
Antipsychotic-related AEs were common among patients with ASD. Further studies to investigate the implications of antipsychotic-related AEs on health and medication adherence are warranted. PROSPERO registration number: (CRD42018083632).
抗精神病药物是自闭症谱系障碍（ASD）患者常用的药物类别。然而，这些药物的安全性尚未得到充分评估。
我们的目的是调查 ASD 患者使用抗精神病药物的安全性和耐受性。
我们检索了 Cochrane 图书馆、MEDLINE、Embase 和 PsycINFO 数据库，检索时间截至 2018 年 1 月。我们纳入了报告 ASD 患者使用第一代或第二代抗精神病药物时发生不良事件（AE）的研究。纳入分析的研究为随机对照试验（RCT）和观察性研究，为比较或非比较研究，并以英文全文发表。本综述的主要结局是报告的任何严重程度的 AE 与抗精神病药物使用的任何剂量相关。对纳入的儿童和青少年参与者的研究进行荟萃分析，以使用随机效应模型估计总体 AE 的汇总患病率和抗精神病药物使用相关 AE 的相对风险（RR）。使用 Cochrane 协作工具和改良的 Newcastle-Ottawa 量表（NOS）分别评估纳入 RCT 和观察性研究的偏倚风险。
共有 54 条引文符合纳入标准，其中 40 项为 RCT，14 项为观察性研究；8 项 RCT 纳入荟萃分析以估计抗精神病药物使用相关 AE 的 RR，7 项观察性研究纳入以估计 AE 的汇总患病率。抗精神病药物治疗的 AE 风险比安慰剂高 22%（RR 1.22；95%置信区间 [CI] 1.11-1.34；I=30.6%；p=0.184）。AE 的估计汇总患病率为 50.5%（95%CI 33-67）。最常报告的 AE 是食欲增加和体重增加，许多参与者因这些 AE 而停药。
ASD 患者中抗精神病药物相关 AE 很常见。需要进一步研究以调查抗精神病药物相关 AE 对健康和药物依从性的影响。PROSPERO 注册号：（CRD42018083632）。
