Increased risk of all-cause mortality associated with domperidone use in Parkinson's patients: a population-based cohort study in the UK

Marina Simeonova, Frank de Vries*, Sander Pouwels, Johanna H. M. Driessen, Hubert G. M. Leufkens, Suzanne M. Cadarette, Andrea M. Burden

*Corresponding author for this work

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Abstract

AimsDomperidone is used to treat gastrointestinal symptoms in patients with Parkinson's disease (PD) and is linked to an increased risk of mortality. We sought to examine the risk of all-cause mortality associated with domperidone exposure in PD.

MethodsWe conducted a cohort study using data from the Clinical Practice Research Datalink database (1987-2011). The first recorded PD diagnosis defined index date. Time-dependent Cox proportional hazards models estimated hazard ratios (HRs) of all-cause mortality associated with domperidone use. PD patients were stratified by domperidone use (current/recent/past), with never used as the referent. Current domperidone users were stratified by daily dose, domperidone duration and other anti-Parkinson's medications. A secondary analysis compared PD patients to matched (1:1) non-PD patients.

ResultsA total of 5114 PD patients were identified. Current use of domperidone among PD patients was associated with a two-fold increase in all-cause mortality (HRadj=2.00, 95% confidence interval [CI]: 1.64-2.45), as compared to patients never exposed to domperidone. All-cause mortality risk was highest in those starting domperidone in the previous month [HRadj=2.97, 95% CI: 2.06-4.27]. When compared to matched non-PD patients, PD was associated with a 43% increased risk of all-cause mortality, yet this increased to a 2.4-fold increased risk among PD patients currently using domperidone.

ConclusionCurrent use of domperidone was associated with a two-fold increased mortality risk in PD patients, as compared to PD patients that never used domperidone. The risk is highest in the first month of use and does not appear to be attributable to PD alone.

Original languageEnglish
Pages (from-to)2551-2561
Number of pages11
JournalBritish Journal of Clinical Pharmacology
Volume84
Issue number11
DOIs
Publication statusPublished - Nov 2018

Keywords

  • drug safety
  • Parkinson's disease
  • pharmacoepidemiology
  • SUDDEN CARDIAC DEATH
  • QTC-PROLONGING DRUGS
  • VENTRICULAR-ARRHYTHMIA
  • DISEASE
  • PHARMACOLOGY
  • DYSFUNCTION
  • PROFILE
  • ARREST

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