Association between Migraines and Prior Proton Pump Inhibitor Use: A Nested Case-Control Study Using a National Health Screening Cohort

Abstract

The effect of proton pump inhibitor (PPI) use on migraine risk remains controversial. We explored the odds of migraines in relation to prior PPI use and treatment duration. Data from the Korean National Health Insurance Service-Health Screening Cohort (2002−2015) were analyzed in this nested case-control study involving 28,159 participants with incident migraines and 112,636 controls (1:4 matched by sex, age, income, and residential region). The baseline covariates were balanced by performing propensity score overlap weighting-based adjustments, and the effect of prior PPI use (past vs. current) and treatment duration (<30 and 30−365 days vs. ≥365 days) on incident migraines was evaluated using logistic regression. In past and current PPI users, prior PPI use raised the likelihood of migraines (adjusted odds ratio [95% confidence interval]: 2.56 [2.36−2.79] and 4.66 [4.29−5.06], respectively). Participants who used PPI for <30, 30−365, or ≥365 days exhibited high odds of migraines (2.49 [2.29−2.72], 4.41 [4.05−4.79], and 4.14 [3.77−4.54], respectively). Incident migraines with or without aura also increased independently of PPI use history or duration. In summary, prior PPI use, irrespective of the elapsed time since use and the duration of use, is possibly associated with incident migraines with or without aura.

Keywords: aura; migraine; nested case-control study; proton pump inhibitors.

Figure 1

Forest plots depicting the association between history of PPI use and a subsequent risk of incident migraines in each subgroup by age, sex, income status, and region of residence.

Figure 2

Forest plots depicting the association between duration of PPI use and a subsequent risk of incident migraines in each subgroup by age, sex, income status, and region of residence.

Figure 3

A schematic illustration of the participant selection process used in the present study. The KNHIS-HSC database includes 514,866 patients, from which a total of 28,159 participants with migraines were matched with 112,636 control participants by age, sex, income status, region of residence, and index date.