Dose-dependent association between proton pump inhibitor use and the risk of migraine: a nationwide matched case-control study
Abstract
BACKGROUND
Proton pump inhibitors (PPIs) are widely prescribed, but their link to migraine risk, especially in Asian populations, remains unclear. This longitudinal study aimed to answer the following question: Does PPI exposure show a dose-dependent risk of migraine, varying by subtype and PPI indication in an Asian population?
METHOD
Using Taiwan's National Health Insurance Research Database (2000-15), we conducted a matched case-control study on PPI exposure. Adults prescribed PPIs for peptic ulcers, gastroesophageal reflux disease, or upper gastrointestinal bleeding were included, excluding those with prior migraines or incomplete data. Controls were matched 1:1 by age, sex, and residence. PPI exposure was measured in cumulative defined daily doses (cDDDs).
RESULT
The study included 22 834 PPI users (11 417 cases, 11 417 controls) with a mean follow-up of 4.1 ± 3.3 years. The study population comprised 65.6% females and 34.4% males, with no significant sex difference (P = 1.000). Mean age was 47.27 ± 15.16 years in cases and 47.42 ± 15.14 years in controls (P = .444). The average interval from PPI initiation to migraine diagnosis was 2.4 ± 1.9 years. Compared with those with the lowest PPI exposure (cDDD ≤30), migraine risk progressively increases with greater cumulative exposure: cDDD 31-120 [aOR = 1.22, 95% confidence interval (CI) = 1.15-1.30], cDDD 121-365 (aOR = 1.42, 95% CI = 1.32-1.52), and cDDD >365 (aOR = 1.60, 95% CI = 1.41-1.80). This dose-dependent…
How strong is the evidence?
Evidence Hub reads this as a case-control, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause.
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