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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重新评估精神分裂症中抗精神病药物作用的变异性：荟萃分析

精神分裂症患者对抗精神病药物的症状反应明显不同，这是执业精神科医生的普遍经验。然而，尚不清楚这种变化是否反映了药物特异性效应的变异性（也称为“治疗效果异质性”），而不是非特异性效应的变异性，例如自然症状波动或安慰剂反应。先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，早期的方法可能无法准确量化治疗效果的异质性，因为它们忽略了一个关键参数：安慰剂反应和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级数据来估计精神分裂症中抗精神病药物治疗效果异质性的相关性和定量特征，从而解决了这一缺点。从耶鲁大学开放数据访问 (YODA) 数据库获得个体患者数据（接受抗精神病药物治疗的 384 人和接受安慰剂的 88 人）。研究层面的数据来自对 66 项临床试验的荟萃分析，其中包括 17,202 名患者。个体患者和研究水平的分析均得出安慰剂反应和治疗效果之间的负相关正负综合征量表 (PANSS) 总分 (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一种，对治疗效果异质性的荟萃分析提供了证据，证明精神分裂症患者之间抗精神病药特异性作用存在显着差异，最高四分位数的患者在 PANSS 上经历了 17.7 分或更多的有益治疗效果总分，而底部四分位数呈现出治疗相对于安慰剂的不利影响。这一具有临床意义的治疗效果异质性的证据表明，对精神分裂症进行个性化抗精神病治疗的努力具有成功的潜力。最高四分位数的患者在 PANSS 总分上经历了 17.7 分或更多的有益治疗效果，而最低四分位数的患者相对于安慰剂表现出治疗的不利影响。这一具有临床意义的治疗效果异质性的证据表明，对精神分裂症进行个性化抗精神病治疗的努力具有成功的潜力。最高四分位数的患者在 PANSS 总分上经历了 17.7 分或更多的有益治疗效果，而最低四分位数的患者相对于安慰剂表现出治疗的不利影响。这一具有临床意义的治疗效果异质性的证据表明，对精神分裂症进行个性化抗精神病治疗的努力具有成功的潜力。