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Ann Epidemiol. 2019 Jul;35:42-47.e1. doi: 10.1016/j.annepidem.2019.04.010. Epub 2019 May 11.

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

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Department of Epidemiology and Biostatistics, University of California, San Francisco, CA. Electronic address:
Department of Medicine, University of Washington, Seattle, WA.
Kaiser Permanente Division of Research, Oakland, CA.
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health and Johns Hopkins University Center on Aging and Health, Baltimore, MD.
Alzheimer's Disease and Chronic Traumatic Encephalopathy Center, Boston University School of Medicine, Boston, MA.
Institute on Aging & Lifelong Health and Department of Psychology, University of Victoria, Victoria BC.
Analysis Group, Boston, MA.
Department of Psychology, University of Michigan, Ann Arbor, MI.
Center for Neuroimaging, Center for Computational Biology and Bioinformatics, Department of Radiology and Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN.
The Michael J. Fox Foundation for Parkinson's Research, New York, NY.
Geriatric Research, Education, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA.
Department of Medicine, University of Washington, Seattle, WA; Kaiser Permanente Washington Health Research Institute, Seattle, WA.



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.


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.


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.


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


Antidepressant medication; Confounding by indication; Depression; Pharmacoepidemiology; Stroke

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