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DT‐01‐03: Common Antidepressant Medications and Risk of Dementia: a Prospective Cohort Study
Author(s) -
Heath Laura M.,
Gray Shelly L.,
Boudreau Denise,
Edwards Karen L.,
Fullerton Stephanie M.,
Thummel Ken,
Larson Eric B.
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.07.009
Subject(s) - dementia , medicine , paroxetine , hazard ratio , mirtazapine , antidepressant , proportional hazards model , cohort , anticholinergic , prospective cohort study , cohort study , population , psychiatry , confidence interval , disease , environmental health , anxiety
Background:The purpose of this study was to determine if antidepressant type was associated with dementia risk. Effects may differ by antidepressant class, as some have known anticholinergic activity (tricyclic antidepressants (TCAs) and paroxetine), which may increase risk, while long-term effects of selective serotonin reuptake inhibitors (SSRIs) are unknown. Methods:Adult Changes in Thought (ACT) is a prospective population-based cohort in an integrated health care delivery system. Initial recruitment occurred from 1994-1996 and 2000-2003, followed by continuous enrollment since 2004. For these analyses eligible participants had at least 10 years of enrollment in the health care system at baseline (N1⁄43342, data through December 31, 2013). Primary exposures were SSRIs (paroxetine vs. others) and TCAs. All other antidepressant classes were grouped together and adjusted for in the models. Computerized pharmacy dispensing data were used to ascertain cumulative medication exposure, defined as total number of standardized daily doses (TSDDs) dispensed over a 10-year period (a rolling window from ACT entry and moving forward in time throughout follow-up). The most recent year was excluded to avoid use related to prodromal symptoms. Dementia risk was analyzed using Cox proportional hazards models adjusted for age via the time axis, and for demographic characteristics, health behaviors, and health status. Results:During a mean follow-up of 7.9 years, 864 participants (25.9%) developed dementia (699 Alzheimer’s disease). An antidepressant was used by 48.6% during the study period. Hazard ratios (HR) and 95% confidence intervals for dementia risk are summarized in Table 1. Notably, paroxetine was associated with increased risk of dementia at all TSDD categories (HRs 1.46-2.06), although the confidence interval crossed 1 for some categories. Other SSRIs and TCAs were not significantly associated with increased risk of dementia. Results were similar for Alzheimer’s disease. Conclusions: Other SSRI and TCA use were not associated with dementia risk. However, paroxetine use was associated with higher risk of dementia and Alzheimer’s disease, even in participants with 90 or fewer TSDDs. Although this association may not be causal due to confounding by indications associated with premorbid symptoms, it is plausible given that other anticholinergic medications have been associated with dementia risk.