Antidepressant Drug Use and Risk of Venous Thromboembolism

STUDY OBJECTIVE: To evaluate the risk of idiopathic venous thromboembolism associated with antidepressant use and to further assess the risk by class of antidepressant and by individual antidepressant drug. DESIGN: Nested case-control study. DATA SOURCE: United Kingdom General Practice Research Database. SUBJECTS: Seven hundred eighty-two case patients with a confirmed diagnosis of venous thromboembolism who were taking an antidepressant drug and 3085 matched control subjects. MEASUREMENTS AND MAIN RESULTS: We identified all people in the database aged 70 years or younger with venous thromboembolism who had filled at least one prescription for an antidepressant drug between 1990 and 2005; up to four control subjects were matched to each case patient by age, sex, practice attended, index date, and duration of computerized medical record. We compared the risks of current and recent use of antidepressant drugs with nonuse of an antidepressant before the index date (date of diagnosis of venous thromboembolism) by using conditional logistic regression. Current exposure to tricyclic antidepressants was associated with a small increased risk of idiopathic venous thromboembolism compared with nonuse (odds ratio [OR] 1.4, 95% confidence interval [CI] 1.1-1.8), whereas we found no increased risk among users of selective serotonin reuptake inhibitors or other antidepressant drugs. When we evaluated individual drugs, we found that amitriptyline conferred an increased risk of thromboembolism (OR 1.7, 95% CI 1.2-2.4) that increased with increasing dose (> 25 mg/day). No other individual antidepressant drug was associated with an increase in risk of venous thromboembolism. CONCLUSION: Current exposure to amitriptyline, particularly at high doses, was associated with an increased risk of idiopathic venous thromboembolism.