Disproportionality analysis from World Health Organization data on migraine-specific medications and cerebrovascular diseases

Background: Migraine is a major cause of population ill health, with an estimated global prevalence of approximately 14–15%. However, given the limited research on the associations between specific migraine medications and adverse cerebrovascular events, this study aimed to investigate these relationships and their impact on cerebrovascular risk.

Methods: This study utilized data from the global pharmacovigilance database, which covers 170 countries from 1968 to 2024. We examined the reporting frequency of adverse cerebrovascular events with 10 migraine medications, with analysis stratified by sex and age. The information component (IC) was calculated using a Bayesian method, while the reporting odds ratio (ROR) was calculated using a frequentist approach to compare reported versus non-reported outcomes.

Results: Among the more than 140 million adverse drug events, 6,080 cases were identified as adverse cerebrovascular events associated with migraine-specific medications. Significant associations with cerebrovascular diseases were observed in both males (ROR, 1.24 [95% CI, 1.19–1.30]; IC 0.31 [IC_0.25, 0.24]) and females (1.73 [1.67–1.79]; 0.78 [0.72]), with most age groups showing significance, except for those 75 years and older. Among the 10 medication categories, 6 categories were associated with adverse cerebrovascular diseases: CGRP antagonists (ROR, 1.22 [95% CI, 1.12–1.33]; IC, 0.28 [IC_0.25,0.14]), ergot alkaloids (3.66 [2.97–4.51]; 1.84 [1.49]), 5-HT₁ receptor agonists (3.33 [2.97–4.51]; 1.72 [1.59]), beta-blockers (2.03 [1.94–2.13]; 1.02 [0.94]), calcium channel blockers (1.46 [1.30–1.64]; 0.54 [0.34]), and clonidine (2.18 [2.04–2.33]; 1.11 [1.00]).

Conclusion: This study found that commonly used migraine medications are significantly associated with an increased risk of cerebrovascular diseases, highlighting the need for careful patient evaluation and selection.