Cumulative dosages of antipsychotic drugs are associated with increased mortality rate in patients with Alzheimer's dementia

OBJECTIVE: We wished to investigate the effects of cumulative dosages of antipsychotic drug in Alzheimer's dementia, when controlling for known risk factors, including current antipsychotic exposure, on all-cause mortality.

METHOD: We utilized a nationwide, population-based, retrospective cohort study design with mortality as outcome in individual patients diagnosed with Alzheimer's dementia.

RESULTS: We included a total of 45 894 patients and followed them for 3 803 996 person-years in total, presenting 27 894 deaths in the study population. Cumulative antipsychotic exposure increased mortality: more than 0 Daily Defined Dosage (DDDs) but less than 90: HR 2.20, 95% CI (2.14-2.27), P < 0.001; more than or equal to 90 DDDs but less than 365: HR 1.81, 95% CI (1.74-1.89), P < 0.001; more than or equal to 365 DDDs but less than 730: HR 1.38, 95% CI (1.428-1.49), P < 0.001; and more than or equal to 730 DDDs: HR 1.06, 95% CI (0.95-1.18), P = 0.322, when controlling for proxy markers of severity, somatic and mental comorbid disorders.

CONCLUSION: In this nationwide cohort study of 45 894 patients diagnosed with Alzheimer's dementia, we found that cumulative dosages of antipsychotic drugs were associated with increased mortality rates.