Magnitude and Determinants of Placebo Response in Acute Migraine Trials: A Systematic Review and Meta-Analysis.

Beyond drug-specific mechanisms, the role of contextual, individual-related, and disease-related factors remains poorly characterized.

除了药物特定机制外，环境、个体相关和疾病相关因素的作用仍然不明确。

We quantified placebo response in randomized controlled trials (RCTs) of acute migraine treatments and identified patient-level, drug-level, and study-level determinants.

我们在急性偏头痛治疗的随机对照试验（RCTs）中量化了安慰剂反应，并识别了患者层面、药物层面和研究层面的决定因素。

Methods

This meta-analytic review searched PubMed, Embase, Cochrane Central, ClinicalTrials.gov, and the European and Japanese Trial Registers from inception to November 2025 for published/unpublished, double-blind, parallel-group, phase 2 or 3 RCTs evaluating acute pharmacologic migraine treatments.

这项荟萃分析审查从建库至2025年11月，通过检索PubMed、Embase、Cochrane Central、ClinicalTrials.gov以及欧洲和日本的试验注册处，寻找已发表/未发表的、双盲的、平行组的、2期或3期的急性药物性偏头痛治疗RCTs。

Placebo rates with 95% CIs and prediction intervals (PIs) were pooled using random-effects models.

使用随机效应模型汇总了安慰剂率及其95%置信区间和预测区间。

Subgroup analyses and meta-regressions explored potential drivers.

亚组分析和元回归探索了潜在的驱动因素。

The primary outcome was 2-hour pain freedom after placebo administration.

主要结果是在给予安慰剂后2小时内的无痛状态。

Secondary outcomes included 2-hour pain relief, sustained pain freedom, rescue medication use, global impression of improvement, and most bothersome symptom (MBS) freedom.

次要结果包括2小时内的疼痛缓解、持续无痛、急救药物使用、改善的整体印象以及最烦恼症状（MBS）的缓解。

Results

We analyzed 126 RCTs published between 1991 and 2025, comprising 24,614 placebo-treated participants (mean age range, 34.8-45.2 years; female, 65.2%-96.9%).

我们分析了1991年至2025年间发表的126项随机对照试验(RCTs)，涵盖了24,614名接受安慰剂治疗的参与者（平均年龄范围，34.8-45.2岁；女性占65.2%-96.9%）。

The pooled 2-hour pain freedom rate was 11% (95% CI 10%-12%; PI: 4%-27%).

综合2小时无痛率达到了11%（95%置信区间10%-12%；预测区间：4%-27%）。

The highest estimates were observed for intranasal (14%; 95% CI 12%-16%) and subcutaneous (13%; 95% CI 8%-20%) administration, compared with oral (10%; 95% CI 9%-12%) (p < 0.05).

观察到鼻腔内（14%；95% 置信区间 12%-16%）和皮下（13%；95% 置信区间 8%-20%）给药的最高估计值，与口服（10%；95% 置信区间 9%-12%）相比（p < 0.05）。

A lower proportion of patients with severe baseline headache and a lower probability of receiving an active treatment were associated with greater responsiveness (β -1.38; 95% CI -2.37 to -0.38; p < 0.01 and β -1.20; 95% CI -2.02 to -0.38; p < 0.005, respectively).

基线时头痛严重的患者比例较低，以及接受活性治疗的可能性较低，与更大的反应性相关（β -1.38；95% 置信区间 -2.37 至 -0.38；p < 0.01 和 β -1.20；95% 置信区间 -2.02 至 -0.38；p < 0.005，分别）。

Placebo response increased significantly over time (β 0.03; 95% CI 0.01-0.04; p < 0.001), even after multivariable adjustment.

安慰剂反应随着时间的推移显著增加（β 0.03; 95% 置信区间 0.01-0.04; p < 0.001），即使在多变量调整后也是如此。

Placebo rates were 34% for 2-hour pain relief, 9% for sustained pain freedom, 52% for rescue medication use, 24% for positive global impression, and 34% for MBS freedom.

安慰剂的反应率分别为：2小时疼痛缓解率为34%，持续无痛率为9%，使用救急药物率为52%，全球印象良好率为24%，MBS自由率为34%。

Exploratory analyses of pain relief showed high placebo responses among non-Caucasian individuals, in Asian countries, and in gepant RCTs.

对疼痛缓解的探索性分析显示，非高加索人种、亚洲国家以及在 gepant 随机对照试验（RCTs）中的安慰剂反应较高。

Discussion

Placebo response represents a substantial and increasing component of outcomes in acute migraine RCTs.

安慰剂反应在急性偏头痛随机对照试验（RCTs）的结果中占据了重要且日益增加的部分。

Improved trial design, standardized communication, and transparent reporting may enhance effect-size interpretation and preserve assay sensitivity in future trials.

改进试验设计、标准化沟通和透明报告可能增强未来试验中效应量的解释并保持检测灵敏度。