Long-Term Antidepressant Use and Dementia Risk: A Propensity Score-Matched Study of Swiss Older Adults, with an Anticholinergic-Specific Analysis

Antidepressants are widely prescribed, with increasing use among older adults. However, evidence on their association with dementia remains inconsistent. This study examines the association between long-term antidepressant use and dementia risk in older adults using a propensity score-matched design, with a separate analysis of long-term tricyclic antidepressant (TCAs) use, given their anticholinergic properties. A retrospective cohort study was conducted using Swiss healthcare claims data (2013–2023) from older adults aged 65 years and above. Long-term antidepressant users (> 2 years) and long-term TCAs users were separately matched to nonusers using variable ratio propensity score matching. The primary outcome was incident dementia, defined by a recorded dementia diagnosis or antidementia drug prescription. Covariates were derived from inpatient and/or outpatient records, depending on the respective variable. A final sample of 19,155 long-term antidepressant users were compared with 20,648 propensity score matched nonusers. After adjusting for covariates, long-term antidepressant use was significantly associated with dementia (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.72–2.15, p < 0.001). Long-term TCAs users also had higher odds of developing dementia compared with nonusers (OR 1.73, 95% CI 1.33–2.25, p < 0.001). Sensitivity analyses largely confirmed these results: long-term antidepressant users had higher odds of developing dementia compared with short-term users (OR 1.23, 95% CI 1.11–1.35, p < 0.001), but for TCA, the difference between long-term and short-term users was not statistically significant (OR 1.25, 95% CI 0.99–1.57, p = 0.059). These findings suggest that long-term antidepressant and long-term TCAs use is associated with an increased risk of dementia in older adults, even after accounting for various comorbidities. This study adds to the ongoing debate on the link between antidepressants and dementia. Future research is needed to further clarify underlying mechanisms and guide clinical practice.