TY - JOUR
T1 - Increased risk of all-cause mortality associated with domperidone use in Parkinson's patients
T2 - a population-based cohort study in the UK
AU - Simeonova, Marina
AU - de Vries, Frank
AU - Pouwels, Sander
AU - Driessen, Johanna H. M.
AU - Leufkens, Hubert G. M.
AU - Cadarette, Suzanne M.
AU - Burden, Andrea M.
PY - 2018/11
Y1 - 2018/11
N2 - 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.
AB - 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.
KW - drug safety
KW - Parkinson's disease
KW - pharmacoepidemiology
KW - SUDDEN CARDIAC DEATH
KW - QTC-PROLONGING DRUGS
KW - VENTRICULAR-ARRHYTHMIA
KW - DISEASE
KW - PHARMACOLOGY
KW - DYSFUNCTION
KW - PROFILE
KW - ARREST
U2 - 10.1111/bcp.13708
DO - 10.1111/bcp.13708
M3 - Article
C2 - 29975795
SN - 0306-5251
VL - 84
SP - 2551
EP - 2561
JO - British Journal of Clinical Pharmacology
JF - British Journal of Clinical Pharmacology
IS - 11
ER -