It is common experience for practising psychiatrists that individuals with schizophrenia vary markedly in their symptomatic response to antipsychotic medication. What is not clear, however, is whether this variation reflects variability of medication-specific effects (also called "treatment effect heterogeneity"), as opposed to variability of non-specific effects such as natural symptom fluctuation or placebo response. Previous meta-analyses found no evidence of treatment effect heterogeneity, suggesting that a "one size fits all" approach may be appropriate and that efforts at developing personalized treatment strategies for schizophrenia are unlikely to succeed. Recent advances indicate, however, that earlier approaches may have been unable to accurately quantify treatment effect heterogeneity due to their neglect of a key parameter: the correlation between placebo response and medication-specific effects. In the present paper, we address this shortcoming by using individual patient data and study-level data to estimate that correlation and quantitatively characterize antipsychotic treatment effect heterogeneity in schizophrenia. Individual patient data (on 384 individuals who were administered antipsychotic treatment and 88 who received placebo) were obtained from the Yale University Open Data Access (YODA) database. Study-level data were obtained from a meta-analysis of 66 clinical trials including 17,202 patients. Both individual patient and study-level analyses yielded a negative correlation between placebo response and treatment effect for the total score on the Positive and Negative Syndrome Scale (PANSS) (ρ=-0.32, p=0.002 and ρ=-0.39, p<0.001, respectively). Using the most conservative of these estimates, a meta-analysis of treatment effect heterogeneity provided evidence of a marked variability in antipsychotic-specific effects between individuals with schizophrenia, with the top quartile of patients experiencing beneficial treatment effects of 17.7 points or more on the PANSS total score, while the bottom quartile presented a detrimental effect of treatment relative to placebo. This evidence of clinically meaningful treatment effect heterogeneity suggests that efforts to personalize antipsychotic treatment of schizophrenia have potential for success.

中文翻译：

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重新评估抗精神病药物对精神分裂症影响的变异性：一项荟萃分析。

执业精神科医生的普遍经验是，精神分裂症患者对抗精神病药物的症状反应存在显着差异。然而，尚不清楚这种变化是否反映了药物特异性效应的可变性（也称为“治疗效果异质性”），而不是非特异性效应的可变性，例如自然症状波动或安慰剂反应。之前的荟萃分析没有发现治疗效果异质性的证据，这表明“一刀切”的方法可能是合适的，并且为精神分裂症制定个性化治疗策略的努力不太可能成功。然而，最近的进展表明，早期的方法可能由于忽视了一个关键参数而无法准确量化治疗效果的异质性：安慰剂反应与药物特异性效应之间的相关性。在本文中，我们通过使用个体患者数据和研究水平数据来估计这种相关性并定量描述精神分裂症中抗精神病药物治疗效果的异质性来解决这一缺点。从耶鲁大学开放数据访问 (YODA) 数据库获得个体患者数据（384 名接受抗精神病药物治疗的患者和 88 名接受安慰剂治疗的患者）。研究水平的数据来自对 66 项临床试验（包括 17,202 名患者）的荟萃分析。个体患者和研究层面的分析均表明，安慰剂反应与治疗效果之间的阳性和阴性症状量表 (PANSS) 总分呈负相关（ρ=-0.32，p=0.002 和 ρ=-0.39，p<0.001） ， 分别）。使用这些估计中最保守的估计，治疗效果异质性的荟萃分析提供了精神分裂症患者之间抗精神病药物特异性效果显着差异的证据，前四分之一的患者在 PANSS 上经历了 17.7 分或更多的有益治疗效果总分，而底部四分位数表示相对于安慰剂的治疗有不利影响。