Associations of Neuropsychiatric Symptoms and Antidepressant Prescription with Survival in Alzheimer's Disease

Abstract

Objective: Depression is associated with increased mortality in community samples. The use of antidepressant medication may also increase mortality, however, it is still unclear whether taking antidepressants before or after a diagnosis of dementia influences survival.

Design: Retrospective.

Setting: A cohort with a diagnosis of Alzheimer disease (AD) from a large mental health and dementia care database in South London, linked to hospitalization and mortality data.

Participants: Mild dementia (Mini-Mental State Examination ≥18/30) at the point of diagnosis.

Measurements: We ascertained antidepressant prescription, either in the 6 months before or after dementia diagnosis, and used the HoNOS65+, a standard clinician-rated measure of patient well-being, to determine depression severity and other neuropsychiatric, physical health, and functional difficulties. We conducted a survival analysis, adjusted for potential confounders and addressed possible confounding by indication through adjusting for a propensity score.

Results: Of 5473 patients with AD, 22.8% were prescribed an antidepressant in a 1-year window around dementia diagnosis. Of these, 2415 (44.1%) died in the follow-up period [mean (standard deviation) 3.5 (2.4) years]. Prescription of an antidepressant, both before and after dementia diagnosis, was significantly associated with higher mortality after adjusting for a broad range of potential confounders including symptom severity, functional status, and physical illness (hazard ratio 1.22; 95% confidence interval 1.08-1.37 for prescription prior to dementia diagnosis; 95% confidence interval 1.04-1.45 for prescription post dementia diagnosis). In stratified analyses, risks remained significant in those without neuropsychiatric symptoms.

Conclusions: The prescription of antidepressants around the time of dementia diagnosis may be a risk factor for mortality.

Keywords: Dementia; antidepressants; depression; mortality.