AHS 2022 | Increased placebo response over time in migraine preventive trials

Treatment efficacy in randomized controlled trials is evaluated by the differential response of treatment and placebo groups, which is the specific treatment effect. Therefore, assessing if there is an increase in placebo response is crucial as it will affect clinical trials. Stewart Tepper, MD, Dartmouth-Hitchcock Medical Center, Lebanon, NH, discusses a systematic literature review and meta-analysis on the increased placebo response over time in migraine preventive trials. Although previous peer-reviewed articles supported an increase in placebo response over time in other neurological conditions, the evaluations in migraine were equivocal. Dr Tepper and his colleagues conducted a comprehensive literature review of randomized, double-blind, placebo-controlled trials evaluating preventive migraine treatments in adults with episodic and chronic migraines published from January 1990 to August 2021. Of the 1455 studies identified, only 84 were eligible. The studies were then divided into oral and injectable studies, depending on the route of drug administration of the placebo. Results showed that for oral studies, there was a statistically significant increase in placebo response by publication across the years. There was no statistically significant difference in placebo response over time for the injectable placebo, but a trend could be observed. When oral and injection studies were combined, a positive but nonsignificant relationship emerged between publication year and ranking of mean change in migraine outcome from baseline in the placebo arm. However, when all outcomes were added, it showed a significant positive correlation between change in the placebo arm from baseline by year. This increase in placebo response mandates larger sample sizes for powering appropriate clinical trials and must be considered when conducting large-scale meta-analyses. This interview took place at the 2022 American Headache Society (AHS) Meeting in Denver, CO.