title: Risk of seizure associated with use of acid-suppressive drugs: An observational cohort study.
abstract: Previous, large, prescription-event monitoring studies in patients receiving PPI therapy recorded instances of convulsion or seizure. The objective of this study was to quantify the relative risk of seizure associated with the use of proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) in a general population, overall and stratified by epilepsy status, and to determine the effects of demographics and comorbidities.
  
  
  
  In this observational study (NCT01744301), patients aged 20-84years in the study period from 1 January 2005 to 31 December 2011 were identified from The Health Improvement Network. In a nested case-control analysis, 8605 patients with seizure were matched to 40000 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression.
  
  
  
  After adjustment, there were no associations between current PPI use and seizure risk in the overall population (OR: 1.05; 95% CI: 0.87-1.27), the subcohort with epilepsy (OR: 0.87; 95% CI: 0.49-1.53), and the subcohort without epilepsy (OR: 1.05; 95% CI: 0.87-1.28). There were no associations between current H2RA use and seizure risk in the overall population (OR: 1.16; 95% CI: 0.62-2.18) and the subcohort without epilepsy (OR: 1.02; 95% CI: 0.51-2.01). Seizures were less frequent in women than in men. Dementia/psychosis, anxiety, depression, and use of anxiolytics, antidepressants, and paracetamol were associated with an increased seizure risk.
  
  
  
  Our study revealed that the use of PPIs and the use of H2RAs were not associated with an increased risk of seizures in the overall population or in the cohorts stratified by epilepsy status.
authors.affiliation: Spanish Centre for Pharmacoepidemiologic Research (CEIFE), Madrid, Spain; Andalusian Bioinformatics Research Centre (CAEBi), Seville, Spain.
authors.forename: María E
authors.initials: ME
authors.lastname: Sáez
authors.affiliation: Spanish Centre for Pharmacoepidemiologic Research (CEIFE), Madrid, Spain; Andalusian Bioinformatics Research Centre (CAEBi), Seville, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Pérez
authors.affiliation: Department of Neurology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
authors.forename: David
authors.initials: D
authors.lastname: Gaist
authors.affiliation: AstraZeneca Gothenburg, Mölndal, Sweden.
authors.forename: Saga
authors.initials: S
authors.lastname: Johansson
authors.affiliation: AstraZeneca Gothenburg, Mölndal, Sweden.
authors.forename: Péter
authors.initials: P
authors.lastname: Nagy
authors.affiliation: Spanish Centre for Pharmacoepidemiologic Research (CEIFE), Madrid, Spain. Electronic address: lagarcia@ceife.es.
authors.forename: Luis A
authors.initials: LA
authors.lastname: García Rodríguez
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D006635:Histamine H2 Antagonists / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D054328:Proton Pump Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D018570:Risk Assessment; D012307:Risk Factors; D012640:Seizures / Q000139:chemically induced*; D012737:Sex Factors; D055815:Young Adult
chemical_list: D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors
keywords: Case–control analysis; Epilepsy; Histamine-2 receptor antagonists; Proton pump inhibitors; Seizures