Association of cerebrovascular events with antidepressant use: a case-crossover study

Am J Psychiatry. 2011 May;168(5):511-21. doi: 10.1176/appi.ajp.2010.10071064. Epub 2011 Mar 15.


Objective: The authors sought to assess the risk of cerebrovascular events associated with use of antidepressant medications.

Method: The authors conducted a case-crossover study of 24,214 patients with stroke enrolled in the National Health Insurance Research Database in Taiwan from 1998 to 2007. The authors compared the rates of antidepressant use during case and control time windows of 7, 14, and 28 days. Adjustments were made for time-dependent variables, such as health system utilization and proposed confounding medications. Stratified analyses were performed for valuing the interaction between the stroke risk of antidepressant use and age, sex, presence of mood disorder, stroke type, severity of chronic illness, and duration of antidepressant treatment. A conditional logistic regression model was used to determine the odds of antidepressant use during case time windows.

Results: The adjusted odds ratio of stroke risk with antidepressant exposure was 1.48 (95% confidence interval=1.37-1.59) using 14-day time windows. Stroke risk was negatively associated with the number of antidepressant prescriptions reported. Use of antidepressants with high inhibition of the serotonin transporter was associated with a greater risk of stroke than use of other types of antidepressants.

Conclusions: These findings suggest that antidepressant use may be associated with an increased risk of stroke. However, the underlying mechanisms remain unclear.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use
  • Antidepressive Agents, Second-Generation / adverse effects
  • Antidepressive Agents, Second-Generation / therapeutic use
  • Antidepressive Agents, Tricyclic / adverse effects
  • Antidepressive Agents, Tricyclic / therapeutic use
  • Depressive Disorder / drug therapy*
  • Female
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Monoamine Oxidase Inhibitors / adverse effects
  • Monoamine Oxidase Inhibitors / therapeutic use
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / adverse effects
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Stroke / chemically induced*
  • Time Factors
  • Young Adult


  • Antidepressive Agents
  • Antidepressive Agents, Second-Generation
  • Antidepressive Agents, Tricyclic
  • Monoamine Oxidase Inhibitors
  • Serotonin Uptake Inhibitors