Short- and Long-term Mortality Risk Associated with the Use of Antipsychotics Among 26,940 Dementia Outpatients: A Population-Based Study

Objective: To investigate short- and long-term mortality risk associated with the use of antipsychotics in dementia outpatients, assessing the risk over specific time frames and quantifying the risk by the individual antipsychotics. 

Methods: This population-based study used data from the Norwegian Prescription Database. The study sample included 26,940 dementia outpatients aged 65 years or older prescribed antidementia drugs and psychotropics from Norwegian pharmacies between 2004 and 2010. 

Results: Cox survival analyses, adjusted for age, gender, mean daily defined dose, and severe medical conditions, showed that antipsychotic use compared with other psychotropics involved approximately twice the mortality risk in outpatients with dementia. Furthermore, these results are consistent for all investigated time points after first dispensing the drugs (hazard ratio [HR](30days) - 2.1 [95% confidence interval {CI}: 1.6-2.9] to HR730-2,400days = 1.7 [95% CI: 1.6-1.9]). Haloperidol was associated with higher mortality risk (HR30days = 1.7 [95% CI: 1.0-3.0] to HR730-2,400days = 1.4 [95% CI: 1.0-1.9]) than risperidone. 

Conclusion: This first study to observe antipsychotic use and mortality in dementia outpatients over more than 6 years clearly shows that antipsychotics involve increased short- and long-term mortality risk. Physicians may justly consider antipsychotics to be the best option for some dementia patients among available nonpharmacologic and pharmacologic treatments. However, although causal conclusions are precluded due to limited adjustments in the analyses, the findings support the current treatment recommendations that antipsychotics should be avoided or used with great caution.