Antipsychotic drug efficacy may have decreased over recent decades. The authors present a meta-analysis of all placebo-controlled trials in patients with acute exacerbations of schizophrenia, and they investigate which trial characteristics have changed over the years and which are moderators of drug-placebo efficacy differences.

The search included multiple electronic databases. The outcomes were overall efficacy (primary outcome); responder and dropout rates; positive, negative, and depressive symptoms; quality of life; functioning; and major side effects. Potential moderators of efficacy were analyzed by meta-regression.

The analysis included 167 double-blind randomized controlled trials with 28,102 mainly chronic participants. The standardized mean difference (SMD) for overall efficacy was 0.47 (95% credible interval 0.42, 0.51), but accounting for small-trial effects and publication bias reduced the SMD to 0.38. At least a “minimal” response occurred in 51% of the antipsychotic group versus 30% in the placebo group, and 23% versus 14% had a “good” response. Positive symptoms (SMD 0.45) improved more than negative symptoms (SMD 0.35) and depression (SMD 0.27). Quality of life (SMD 0.35) and functioning (SMD 0.34) improved even in the short term. Antipsychotics differed substantially in side effects. Of the response predictors analyzed, 16 trial characteristics changed over the decades. However, in a multivariable meta-regression, only industry sponsorship and increasing placebo response were significant moderators of effect sizes. Drug response remained stable over time.

Approximately twice as many patients improved with antipsychotics as with placebo, but only a minority experienced a good response. Effect sizes were reduced by industry sponsorship and increasing placebo response, not decreasing drug response. Drug development may benefit from smaller samples but better-selected patients.

近几十年来，抗精神病药的疗效可能有所下降。作者对所有患有精神分裂症急性加重患者的安慰剂对照试验进行了荟萃分析，他们研究了哪些试验特征多年来发生了变化，哪些是药物-安慰剂疗效差异的调节剂。

搜索包括多个电子数据库。结果为总体疗效（主要结果）；响应者和辍学率；阳性，阴性和抑郁症状；生活质量; 运作 和主要的副作用。通过meta回归分析潜在的疗效调节剂。

分析包括167项双盲随机对照试验，其中28,102名主要为慢性参与者。总体功效的标准均值差（SMD）为0.47（95％可信区间0.42，0.51），但考虑到小试验效应和发表偏倚，SMD降至0.38。至少51％的抗精神病药组发生了“最低”反应，而安慰剂组为30％，而23％相对于14％发生了“良好”反应。阳性症状（SMD 0.45）比阴性症状（SMD 0.35）和抑郁症（SMD 0.27）改善得更多。即使在短期内，生活质量（SMD 0.35）和功能（SMD 0.34）也得到了改善。抗精神病药的副作用大不相同。在分析的反应预测因素中，数十年来变化了16个试验特征。但是，在多变量元回归中，只有行业赞助和增加的安慰剂反应才是效应大小的重要调节剂。药物反应随时间保持稳定。

服用抗精神病药的患者大约是安慰剂的两倍，但只有少数患者能收到良好的反应。通过行业赞助和增加安慰剂反应（而不是减少药物反应）来减少效应的大小。药物开发可能受益于较小的样本但选择更好的患者。