Side effects of antipsychotic drugs play a key role in nonadherence of treatment in schizophrenia spectrum disorders (SSD). While clinical observations suggest that side effect variability between patients may be considerable, statistical evidence is required to confirm this. Here, we hypothesized to find larger side effect variability under treatment compared with control. We included double-blind, placebo-controlled, randomized controlled trials (RCTs) of adults with a diagnosis of SSD treated with 1 out of 14 antipsychotics. Standard deviations of the pre-post treatment differences of weight gain, prolactin levels, and corrected QT (QTc) times were extracted. The outcome measure was the variability ratio of treatment to control for individual antipsychotic drugs and the overall variability ratio of treatment to control across RCTs. Individual variability ratios were weighted by the inverse-variance method and entered into a random-effects model. We included N = 16 578 patients for weight gain, N = 16 633 patients for prolactin levels, and N = 10 384 patients for QTc time. Variability ratios (VR) were significantly increased for weight gain (VR = 1.08; 95% CI: 1.02–1.14; P = .004) and prolactin levels (VR = 1.38; 95% CI: 1.17–1.62; P < .001) but did not reach significance for QTc time (VR = 1.05; 95% CI: 0.98–1.12; P = 0.135). We found marked differences between individual antipsychotics and increased variability in side effects in patients under treatment with antipsychotics suggesting that subgroups of patients or individual patients may benefit from treatment allocation through stratified or personalized medicine.

中文翻译：

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检查精神分裂症谱系障碍抗精神病药物治疗的副作用变异性：方差荟萃分析


抗精神病药物的副作用在精神分裂症谱系障碍（SSD）治疗不依从性中发挥着关键作用。虽然临床观察表明患者之间的副作用差异可能很大，但需要统计证据来证实这一点。在这里，我们假设与对照组相比，治疗下的副作用变异性更大。我们纳入了双盲、安慰剂对照、随机对照试验 (RCT)，对象是诊断为 SSD 并接受 14 种抗精神病药物中的 1 种治疗的成人。提取治疗前后体重增加、催乳素水平和校正 QT (QTc) 时间差异的标准差。结果测量是单个抗精神病药物的治疗与对照的变异性比率以及随机对照试验中治疗与对照的总体变异性比率。个体变异率通过逆方差方法加权并输入随机效应模型。我们纳入了 N = 16 578 名体重增加患者、N = 16 633 名催乳素水平患者和 N = 10 384 名 QTc 时间患者。体重增加（VR = 1.08；95% CI：1.02–1.14；P = .004）和催乳素水平（VR = 1.38；95% CI：1.17–1.62；P < .001）的变异比（VR）显着增加）但 QTc 时间未达到显着性（VR = 1.05；95% CI：0.98–1.12；P = 0.135）。我们发现个体抗精神病药物之间存在显着差异，并且接受抗精神病药物治疗的患者副作用的变异性增加，这表明患者亚组或个体患者可能受益于分层或个性化医疗的治疗分配。