title: Comparative risk of death in older adults treated with antipsychotics: A population-based cohort study.
abstract: Although the use of antipsychotics has been associated with an increased risk of death, data on the safety of individual substances is scarce. We thus aimed to compare the risk of death in new users of individual antipsychotics aged =>65 years and conducted a cohort study in the German Pharmacoepidemiological Research Database between 2005 and 2011. Patients were followed from initiation of treatment until death, 90 days after cohort entry, end of insurance or the end of the study period. Multivariable cox regression was used to estimate confounder adjusted hazard ratios (aHR) of death for 14 individual antipsychotics compared to risperidone. In sensitivity analyses, we also applied high-dimensional propensity score (HDPS) methods to explore possible unmeasured confounding. In a cohort of 137,713 new users of antipsychotics, a higher risk of death was found for haloperidol (aHR: 1.45; 95% confidence interval: 1.35-1.55), levomepromazine (aHR: 1.34; 1.16-1.54), zuclopenthixol (aHR: 1.32; 1.02-1.72) and to a lesser extent for melperone (aHR: 1.13; 1.07-1.19) compared to risperidone. Lower risks were observed for quetiapine, prothipendyl, olanzapine, tiapride, clozapine, perazine and flupentixol. In subgroup analyses, levomepromazine and chlorprothixene were only associated with a higher risk of death in patients aged =>80 years and with dementia. The application of HDPS methods did not substantially change the results. In conclusion, our study suggests that initiation of haloperidol, levomepromazine, zuclopenthixol and chlorprothixene treatment is associated with an increased risk of death compared to risperidone and should be avoided in older patients except in palliative care when treatment alternatives are available.
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology - BIPS GmbH, Achterstraße 30, 28359 Bremen, Germany. Electronic address: schmedt@bips.uni-bremen.de.
authors.forename: Niklas
authors.initials: N
authors.lastname: Schmedt
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology - BIPS GmbH, Achterstraße 30, 28359 Bremen, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Kollhorst
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology - BIPS GmbH, Achterstraße 30, 28359 Bremen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Enders
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology - BIPS GmbH, Achterstraße 30, 28359 Bremen, Germany; Carl von Ossietzky University Oldenburg, Department of Health Services Research Oldenburg, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Jobski
authors.affiliation: Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175 Bonn, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Krappweis
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology - BIPS GmbH, Achterstraße 30, 28359 Bremen, Germany.
authors.forename: Edeltraut
authors.initials: E
authors.lastname: Garbe
authors.affiliation: Leibniz Institute for Prevention Research and Epidemiology - BIPS GmbH, Achterstraße 30, 28359 Bremen, Germany.
authors.forename: Tania
authors.initials: T
authors.lastname: Schink
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D003704:Dementia / Q000188:drug therapy / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D005858:Germany; D006801:Humans; D008297:Male; D009026:Mortality; D057216:Propensity Score; D016016:Proportional Hazards Models; D012306:Risk; D012737:Sex Factors
chemical_list: D014150:Antipsychotic Agents
keywords: Adverse drug reaction; Antipsychotic; Death; Dementia; Elderly; Mortality