Proton pump inhibitor-related headaches: a nationwide population-based case-crossover study in Taiwan.
BACKGROUND
Headaches resulting from proton pump inhibitor (PPI) use could cause discontinuation of PPI in as many as 40% of patients who experience such headaches. Previous studies focusing on acute headache risk from PPI use are rare and limited to clinical trials of a single PPI.


OBJECTIVE
To investigate the association between PPI use and headache with a nationwide population-based case-crossover study.


METHODS
Records containing the first diagnosis of any headache, including migraine and tension-type headaches, were retrieved from Taiwan National Health Insurance Database (1998-2010). We compared the rates of PPI use for cases and controls during time windows of 7, 14, and 28 days. The adjusted self-matched odds ratios (ORs) and 95% confidence intervals (CIs) from a conditional logistic regression model were used to determine the association between PPI use and headache.


RESULTS
Overall, 314,210 patients with an initial diagnosis of any headache during the study period were enrolled. The adjusted ORs for headache risk after PPI exposure were calculated for three time periods (within 7 days=1.41, p=0.002, 95% CI 1.14-1.74; within 14 days=1.36, p<0.001, 95% CI 1.16-1.59; within 28 days=1.20, p=0.002, 95% CI 1.07-1.35). Subgroup analyses showed female patients had an increased risk of headache. Among PPIs, lansoprazole and esomeprazole had the highest risks of headache incidence, which were similar to that of nitrates.


CONCLUSIONS
PPI usage is associated with an increased risk for acute headache. Female patients and use of lansoprazole or esomeprazole present the greatest risks of headache.
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taiwan Department of Medical Education, Taipei Veterans General Hospital, Taiwan School of Medicine, National Yang-Ming University, Taiwan.
Jen-Feng
JF
Liang
School of Medicine, National Yang-Ming University, Taiwan Department of Nephrology, Taipei City Hospital Heping Fuyou Branch, Taiwan.
Yung-Tai
YT
Chen
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taiwan School of Medicine, National Yang-Ming University, Taiwan.
Jong-Ling
JL
Fuh
School of Medicine, National Yang-Ming University, Taiwan Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taiwan.
Szu-Yuan
SY
Li
School of Medicine, National Yang-Ming University, Taiwan Department of Family Medicine, Taipei Veterans General Hospital, Taiwan.
Tzeng-Ji
TJ
Chen
School of Health Care Administration, Taipei Medical University, Taiwan.
Chao-Hsiun
CH
Tang
Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taiwan School of Medicine, National Yang-Ming University, Taiwan Institute of Brain Science, National Yang-Ming University, Taiwan Brain Research Center, National Yang-Ming University, Taiwan sjwang@vghtpe.gov.tw.
Shuu-Jiun
SJ
Wang
D000328:Adult; D016022:Case-Control Studies; D018592:Cross-Over Studies; D005260:Female; D006261:Headache / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D054328:Proton Pump Inhibitors / Q000009:adverse effects*; D013624:Taiwan / Q000453:epidemiology
D054328:Proton Pump Inhibitors
Headache; Taiwan; incidence; proton pump inhibitor; risk