Antidepressant Use and Risk of Recurrent Stroke: A Population-Based Nested Case-Control Study

Objective: Antidepressants may carry an increased risk for incident stroke, but there is little safety evidence regarding poststroke antidepressant use. This study aimed to examine whether antidepressants are associated with an increased risk of stroke recurrence.

Method: A population-based nested case-control study was conducted analyzing the Taiwan universal health care claims database from January 1, 2000, to December 31, 2008. We followed up 19,825 patients who survived a first admission for stroke at the age of ≥ 18 years, among which 3,536 hospitalized cases with stroke recurrence (ICD-9-CM codes 430.xx-437.xx) were identified and individually matched to 6,679 randomly-selected controls. Multivariate conditional logistic regression models were used to characterize the risk associated with antidepressant use.

Results: The study cohort had a mean age of 66 years and was followed up for a median of 2.9 person-years. Use of any tricyclic antidepressants (TCAs) was associated with a 1.41-fold (95% CI, 1.19-1.67) increased risk of stroke recurrence, whereas any use of selective serotonin reuptake inhibitors (SSRIs) or other antidepressants showed no association. Stopping TCAs for 1-30 days was associated with a 1.87-fold (95% CI, 1.22-2.86) increased risk of stroke recurrence, and the risk was attenuated for a longer discontinuation. The stroke risk associated with TCA use was not present in a dose-dependent or duration-dependent manner.

Conclusions: Use of TCAs, but not SSRIs or other antidepressants, was associated with an increased risk of stroke recurrence. The risk is particularly elevated with abrupt cessation of TCA therapy. Health care professionals should be vigilant to that risk during TCA therapy in poststroke patients.