Antidepressant Monotherapy in Elderly Linked to Increased Incident Dementia

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Although 11.0% of individuals taking antidepressants developed dementia, only 2.6% of the unexposed sample went on to be diagnosed with dementia.

A prospective cohort study published in the American Journal of Geriatric Psychiatry found that exposure to antidepressants in old age may increase risk for incident dementia.

The research team examined patients aged at least 60 years with no history of dementia who did not receive antidepressants in the prior year. The eligible sample was drawn from an Israeli health maintenance organization, allowing for follow-up on dementia diagnoses and antidepressant medication exposure. Covariates included a wide range of demographic and medical factors, and statistical analysis involved Cox regression models, Kaplan-Meier models, and sensitivity analyses.

In the final sample (N=71,515; mean age, 71.4±7.4 years; 49.6% men), 3.0% (n=2175) developed dementia in the follow-up period averaging 4.5 years. The antidepressant-exposed group (n=3688) was slightly older, more female, wealthier, and more likely to be diagnosed with somatic or psychiatric conditions.

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Although 11.0% (n=407) of individuals exposed to antidepressants developed dementia during the follow-up period, only 2.6% (n=1768) of individuals not exposed to antidepressants went on to develop dementia in the same period.

The researchers found that there was a significant difference in the risk for incident dementia for the group exposed to antidepressants compared with those who were not (adjusted HR, 3.43; 95% Wald CI, 3.04-3.88; P <.001). Notably, this result was replicated in all sensitivity analyses.

The study validated results from prior observational studies, which also demonstrated that antidepressant use may be linked to an elevated risk for dementia. However, the study was limited by the potential of results to mimic associations between depression and dementia, rather than antidepressant effects, as well as possible underdiagnosis of dementia in the sample.

“Clinicians, caregivers, and patients may wish to consider this potential negative consequence of antidepressant exposure with the objective of balancing the adverse events and symptomatic benefits of monotherapeutic antidepressant medication in old age,” the study authors recommended.


Kodesh A, Sandin S, Reichenberg A, et al. Exposure to antidepressant medication and the risk of incident dementia. Am J Geriatr Psychiatry. 2019;27(11):1177-1188.