A Nationwide Cohort Study on Antidepressant Use and Stroke Risk in Young Adults Aged 18–44 Years

PURPOSE: Although serious adverse reactions to antidepressants, including stroke, are rare, they have gained increased attention. Many patients start antidepressant treatment at a young age, yet stroke risk among them remains understudied. This study aimed to assess stroke risk associated with antidepressant use across age groups, antidepressant classes, and treatment indications. METHODS: We conducted a cohort study using a new user approach, including adults aged 18-44 years in 2018. Overall, 119,751 antidepressant users and 119,751 non-users were matched by age, sex, and date of treatment initiation. Antidepressants, classified as N06A in the WHO Anatomical Therapeutic Chemical Classification System, were selected. The primary endpoint was the first stroke event within 180 days of treatment initiation. FINDING: Antidepressant use was associated with an increased stroke risk (hazard ratio [HR], 4.33; 95% confidence interval [CI] 2.30-8.14), particularly ischemic stroke (HR, 7.02; 95% CI 3.18-15.49), than hemorrhagic stroke (HR, 1.63; 95% CI 0.60-4.39). Elevated stroke risk was observed among users of tricyclic antidepressants and serotonin antagonist and reuptake inhibitors but not among users of selective serotonin or serotonin-norepinephrine reuptake inhibitors. A significantly higher stroke risk was noted among antidepressant users without psychiatric disorders (HR, 5.47; 95% CI, 2.58-11.61) or neurological disorders (HR, 4.10; 95% CI, 2.12-7.95) than among non-users. IMPLICATIONS: Antidepressant use was associated with increased stroke risk in adults aged 18-44 years. However, the findings were limited by potential biases in administrative data and a lack of adjustment for socioeconomic and geographic disparities.