Antipsychotic drug use is associated with a 60% increased risk of mortality among persons with Alzheimer's disease, shows a University of Eastern Finland study.
The risk was highest at the beginning of drug use and remained increased in long-term use. Use of two or more antipsychotic drugs concomitantly was associated with almost two times higher risk of mortality than monotherapy.
The study compared the risk of mortality between the most commonly used antipsychotic drugs. Haloperidol was associated with highest risk of mortality, and the use of higher doses of haloperidol and risperidone were associated with an increased risk of mortality compared with low-dose risperidone use.
The association of antipsychotic drug use with mortality was investigated in the Finnish nationwide MEDALZ study including community-dwelling persons diagnosed with Alzheimer’s disease between 2005 and 2011. Of 57,755 persons, 27% started antipsychotic drug use during the follow-up. The register-based study was restricted to persons who did not use antipsychotics during the year preceding the start of follow-up, did not have history of a psychiatric disorder, and did not have active cancer at the start of follow-up.
The results of this study are in line with many previous studies. The first warnings of an increased risk of mortality among antipsychotic users were issued over 10 years ago. This study provides new knowledge on the risk of mortality during long-term use and during concomitant use of two or more antipsychotic drugs.
The study confirms current recommendations that antipsychotic drugs should be used only for the most difficult behavioural symptoms of dementia, such as agitation and aggression, and the duration of use should be limited. Furthermore, the lowest effective doses are recommended, and concomitant use of two or more antipsychotics should be avoided.
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
Marjaana Koponen, Heidi Taipale, Piia Lavikainen, Antti Tanskanen, Jari Tiihonen, Anna-Maija Tolppanen, Riitta Ahonen, Sirpa Hartikainen
[link url="https://www.uef.fi/en/-/psykoosilaakkeiden-kaytto-lisaa-kuolemanriskia-alzheimerin-tautia-sairastavilla"]University of Eastern Finland material[/link]
[link url="http://content.iospress.com/articles/journal-of-alzheimers-disease/jad160671"]Journal of Alzheimer’s Disease abstract[/link]