Initiation of antidepressant medication and risk of incident stroke: using the Adult Changes in Thought cohort to address time-varying confounding

Purpose

Depression strongly predicts stroke incidence, suggesting that treating depression may reduce stroke risk. Antidepressant medications, however, may increase stroke risk via direct pathways. Previous evidence on antidepressant medication and stroke incidence is mixed. We evaluated associations between antidepressant use and incident stroke.

Methods

For 2302 Adult Changes in Thought cohort participants with no stroke at study entry, we characterized antidepressant use from pharmacy records, biennial depressive symptoms with a 10-item Centers for Epidemiologic Study-Depression scale, and incident strokes from ICD codes. We used discrete-time survival models with inverse probability weighting to compare stroke risk associated with filling antidepressant prescriptions and by medication category: tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors, or other.

Results

Over an average 8.4-year follow-up, 441 incident strokes occurred. Filling antidepressant medications 3+ times versus 0-2 times predicted 35% increased odds of stroke (OR = 1.35; 95% CI: 0.98, 1.66). Use of TCAs was associated with stroke onset (OR per 10 fills = 1.28; CI: 1.04, 1.57), but use of selective serotonin reuptake inhibitors (OR = 0.98; CI: 0.80, 1.20) or other antidepressants (OR = 0.99; CI: 0.67, 1.45) was not.

Conclusions

Although patients who received antidepressant medication were at higher risk of stroke, this association appeared specific to TCA prescriptions.