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Competing hypotheses have been formulated about a possible association between selective serotonin reuptake inhibitors (SSRIs) and ischemic stroke. However, the relationship between antidepressant drug use and ischemic stroke is still unclear. The aim of the study was to assess the association between the use of different types of antidepressants and the risk of ischemic stroke in elderly outpatients.A population-based, nested, case-control study was conducted in persons 65 years and older in the Integrated Primary Care Information database (1996-2005). Cases were all patients with a validated first ischemic stroke. Controls were matched on year of birth, sex, and index date. Exposure to antidepressants was divided in current, past, and nonuse and further categorized by type (SSRI, tricyclic, and other antidepressants), dose, and duration. Conditional logistic regression was used to compare the risk of ischemic stroke between users of antidepressants and nonusers.Overall, 996 incident ischemic strokes were identified. Current use of SSRIs was associated with a significantly increased risk as compared with nonuse (odds ratio, 1.55; 95% confidence interval, 1.07-2.25) in elderly patients, particularly when used for less than six months. No associations were observed for current use of tricyclic and other antidepressant drugs.To summarize, compared with nonuse, only SSRI use seems to be associated with an increased risk of ischemic stroke in elderly patients, particularly as a short-term effect.