Increased all-cause mortality with use of psychotropic medication in dementia patients and controls: A population-based register study

We aimed to evaluate all-cause mortality of middle-aged and elderly subjects diagnosed with dementia and treated with psychotropic drugs as compared with controls subjects. Using data from the Danish National Patient Registry, n=26,821 adults with a diagnosis of dementia were included. They were compared with 44,286 control subjects with a minimum follow-up of four years and matched on age, gender, marital status, and community location. Information about psychotropic medication use (benzodiazepines, antidepressants, antipsychotics) was obtained from the Danish Medicinal Product Statistics. All-cause mortality was higher in patients with dementia as compared to control subjects. Mortality hazard ratios were increased for subjects prescribed serotonergic antidepressant drugs (respectively, HR=1.355 (SD=0.023), P=0.001 in patients; HR=1.808 (0.033), P<0.001 in controls), tricyclic antidepressants (HR=1.004 (0.046), P=0.925; HR=1.406 (0.061), P<0.001), benzodiazepines (HR=1.131 (0.039), P=0.060); HR=1.362 (0.028), P<0.001), benzodiazepine-like drugs (HR=1.108 (0.031), P=0.078; HR=1.564 (0.037, P<0.001), first-generation antipsychotics (HR=1.183 (0.074), P=0.022; HR=2.026 (0.114), P<0.001), and second-generation antipsychotics (HR=1.380 (0.042), P<0.001; HR=1.785 (0.088), P<0.001), as compared with no drug use. Interaction analysis suggested statistically significantly higher mortality hazard ratios for most classes of psychotropic drugs in controls than in dementia patients. We found that use of psychotropic drugs is associated with increased all-cause mortality in both patients with dementia and control subjects. Thus, the frequently reported increased mortality with antipsychotic drugs in dementia is not restricted to subjects with impaired cognition and is not restricted to only one class of psychotropic drugs.