Placebo Response in Acute and Prophylactic Treatment of Migraine: A Systematic Review and Meta-Analysis Covering 36...

The authors identified and meta-analyzed 84 acute and 42 prophylactic systematically selected RCTs on antimigraine drugs between 1988 and 2024, with a total of 25,542 placebo recipients, analyzed separately for episodic and chronic migraine in adults and children. Placebo response rates in adults were 13% for "Pain Free" and 35% for "Pain Relief" in acute RCTs, and a reduction of -2.83 "monthly migraine days" and -3.64 "monthly headache days" in prophylactic RCTs was observed. The "≥50% responder rate for monthly migraine days" was 28%. In children, placebo responses were almost twice as high. Other important determinants of placebo response were the stringency of the endpoint definition (the milder, the higher), the migraine subtype, and the route of administration. Most acute and older prophylactic RCTs did not meet current strict reporting standards and analysis requirements. This may have biased placebo responses and should be addressed in future studies.