title: Risk of Mortality Associated with Antipsychotic Monotherapy and Polypharmacy Among Community-Dwelling Persons with Alzheimer's Disease.
abstract: We aimed to analyze the risk of non-cancer mortality according to duration of antipsychotic use and to compare the risk associated with polypharmacy and monotherapy among community-dwellers with Alzheimer's disease (AD). The risk of mortality between most frequently used antipsychotic drugs was compared. Data from a nationwide register-based MEDALZ study that included all 70,718 community-dwellers newly diagnosed with AD during 2005-2011 in Finland was utilized. Death, excluding cancer as direct cause of death, was extracted from Causes of Death Register. Incident antipsychotic use was compared with time without antipsychotics with Cox proportional hazard models. Antipsychotic use was associated with an increased risk of mortality (adjusted hazard ratio [aHR] 1.61; 95% Confidence Interval [CI] 1.53-1.70). The absolute difference in mortality rate was 4.58 (95% CI 4.53-4.63) deaths per 100 person-years. The risk of mortality was increased from the first days of use and attenuated gradually but remained increased even after two years of use (aHR 1.30; 95% CI 1.16-1.46). Compared with nonuse, antipsychotic polypharmacy (aHR 2.88; 95% CI 2.38-3.49) was associated with an increased risk of mortality than monotherapy (aHR 1.57; 95% CI 1.49-1.66). Haloperidol was associated with higher risk of mortality (aHR 1.52; 95% CI 1.14-2.02) and quetiapine with lower risk (aHR 0.84; 95% CI 0.75-0.94) compared with risperidone. In conclusion, the findings support current treatment guidelines on having a high threshold for antipsychotic initiation among persons with AD. Antipsychotic polypharmacy and long-term use should be avoided and drug choice should be weighed against risk/benefit evidence.
authors.affiliation: Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland.|School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Marjaana
authors.initials: M
authors.lastname: Koponen
authors.affiliation: Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland.|School of Pharmacy, University of Eastern Finland, Kuopio, Finland.|Research Centre for Comparative Effectiveness and Patient Safety (RECEPS), University of Eastern Finland, Kuopio, Finland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Taipale
authors.affiliation: Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland.|Department of Pharmacology, Drug Development and Therapeutics, University of Turku, Turku, Finland.
authors.forename: Piia
authors.initials: P
authors.lastname: Lavikainen
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|National Institute for Health and Welfare, Helsinki, Finland.|Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Tanskanen
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Kuopio, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Tiihonen
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.|Research Centre for Comparative Effectiveness and Patient Safety (RECEPS), University of Eastern Finland, Kuopio, Finland.
authors.forename: Anna-Maija
authors.initials: AM
authors.lastname: Tolppanen
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Ahonen
authors.affiliation: Kuopio Research Centre of Geriatric Care, University of Eastern Finland, Kuopio, Finland.|School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Sirpa
authors.initials: S
authors.lastname: Hartikainen
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality*; D014150:Antipsychotic Agents / Q000009:adverse effects*; D015331:Cohort Studies; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D057187:Independent Living; D008297:Male; D008875:Middle Aged; D019338:Polypharmacy; D016016:Proportional Hazards Models; D012042:Registries; D012307:Risk Factors; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents
keywords: Alzheimer’s disease; antipsychotics; mortality; pharmacoepidemiology