Frank J. Wolters

INTRODUCTION We aimed to assess the effect of antidepressant use on dementia risk, cognitive decline, and brain atrophy. METHODS In this prospective cohort study, we included 5511 dementia‐free participants (Mini‐Mental State Examination [MMSE] > 25) of the Rotterdam study (57.5% women, mean age 70.6 years). Antidepressant use was extracted from pharmacy records from 1991 until baseline (2002–2008). Incident dementia was monitored from baseline until 2018, with repeated cognitive assessment and magnetic resonance imaging (MRI) every 4 years. RESULTS Compared to never use, any antidepressant use was not associated with dementia risk (hazard ratio [HR] 1.14, 95% confidence interval [CI] 0.92–1.41), or with accelerated cognitive decline or atrophy of white and gray matter. Compared to never use, dementia risk was somewhat higher with tricyclic antidepressants (HR 1.36, 95% CI 1.01–1.83) than with selective serotonin reuptake inhibitors (HR 1.12, 95% CI 0.81–1.54), but without dose–response relationships, accelerated cognitive decline, or atrophy in either group. DISCUSSION Antidepressant medication in adults without indication of cognitive impairment was not consistently associated with long‐term adverse cognitive effects. Highlights Antidepressant medications are frequently prescribed, especially among older adults. In this study, antidepressant use was not associated with long‐term dementia risk. Antidepressant use was not associated with cognitive decline or brain atrophy. Our results support safe prescription in an older, cognitively healthy population.