Increased risk of all-cause mortality associated with domperidone use in Parkinson’s patients: a population-based cohort study in the UK.
AIMS: Domperidone 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.
METHODS: We 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 Ratio's (HRs) of all-cause mortality associated with domperidone use. PD patients were stratified by domperidone use (current/recent/past), with never use 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.
RESULTS: A total of 5,114 PD patients were identified. Current use of domperidone among PD patients was associated with a 2-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.
CONCLUSION: Current use of domperidone was associated with a 2-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.
|ジャーナル名||British journal of clinical pharmacology|
|投稿者||Simeonova, Marina; de Vries, Frank; Pouwels, Sander; Driessen, Johanna H M; Leufkens, Hubert G M; Cadarette, Suzanne M; Burden, Andrea M|
|組織名||Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.;Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of;Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.;Care and Public Health Research Institute (CAPHRI), Maastricht, The Netherlands.;Department of Clinical Pharmacy and Toxicology, Maastricht University Medical;Centre Maastricht, The Netherlands.;NUTRIM School Maastricht, the Netherlands. for Nutrition and Translational;Research in Metabolism, Maastricht University, The Netherlands.;Institute of Pharmaceutical Sciences, Department of Chemistry and Applied;Biosciences, ETH Zurich, Switzerland.|