Hemorrhagic stroke associated with antidepressant use in patients with depression: does degree of serotonin reuptake inhibition matter?

Pharmacoepidemiol Drug Saf. 2009 Mar;18(3):196-202. doi: 10.1002/pds.1699.


Objective: This study aimed to determine whether the degree of serotonin (5-HT) reuptake inhibition affects risk of hemorrhagic stroke associated with antidepressant use in patients with depression.

Method: A population-based, nested case-control study was performed using a managed care medical claims database. Ninety two depressed patients with a diagnosis of hemorrhagic stroke were identified and matched with 552 controls by age, sex, and year of index date of depression (IDD). Diagnoses of depression, hemorrhagic stroke, and other medical comorbidities were identified using ICD-9 codes. Antidepressants were classified as high, medium, or low reuptake inhibition based on their affinities for the 5-HT reuptake transporter, determined using their respective equilibrium dissociation constants (K(D); high: K(D) < 1 nM; medium: 1 <or= K(D) < 10 nM; low: K(D) >or= 10 nM). Conditional logistic regression analysis was performed to estimate the crude and adjusted odds ratios (ORs) with 95% confidence intervals (CIs) of the risk of hemorrhagic stroke.

Results: Compared to non-users of antidepressants, risk of hemorrhagic stroke did not significantly differ between patients who had ever used antidepressants with high (OR = 0.82; 95% CI = 0.44-1.55), medium (OR = 0.93; 95% CI = 0.37-2.31), or low (OR = 0.38; 95% CI = 0.11-1.41) 5-HTT inhibition.

Conclusion: Risk of hemorrhagic stroke associated with antidepressant use may not be related to an antidepressant's degree of 5-HT reuptake inhibition. Given the limitations of this study, additional studies are needed to confirm these findings.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use
  • Cerebral Hemorrhage / chemically induced*
  • Cerebral Hemorrhage / epidemiology
  • Databases, Factual
  • Depression / drug therapy
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Serotonin Uptake Inhibitors / adverse effects*
  • Serotonin Uptake Inhibitors / therapeutic use
  • Stroke / chemically induced*
  • Stroke / epidemiology
  • United States / epidemiology


  • Antidepressive Agents
  • Serotonin Uptake Inhibitors