SSRI treatment-associated stroke: causality assessment in two cases

Ann Pharmacother. 2004 Jul-Aug;38(7-8):1197-201. doi: 10.1345/aph.1D624. Epub 2004 May 18.


Objective: To assess the probability of cerebrovascular adverse drug reactions (CV-ADRs) due to treatment with selective serotonin-reuptake inhibitors (SSRIs) using 2 causality methods. case summaries: Two patients with the possibility of SSRI-related stroke were referred for causality assessment. Causality assessment was performed using an adverse drug reaction probability scale, as well as clinical and radiologic parameters. A 31-year-old white man, who had been receiving paroxetine 200 mg/day over a period of 3 years, developed ischemic stroke involving left middle cerebral artery. The second patient was a 46-year-old white woman with a history of recurrent depression who developed delirium and ischemic stroke while she was taking a combination of paroxetine 50 mg/day, trazodone 200 mg/day, and bupropion 150 mg/day.

Discussion: Carotid and cardiothromboembolism were found to be the major etiological factors for ischemic stroke. Accounting for the temporal relation, prior reports of SSRI treatment-associated CV-ADRs, and the pharmacologic action of serotonin on coagulation and the vascular system, the possible contribution of SSRIs to stroke in these patients was considered. An objective causality assessment using the Naranjo probability scale revealed that a CV-ADR was possible. However, the nature of the stroke, plus clinical and radiologic findings, were inconsistent with known pathophysiologic mechanisms linking SSRIs and stroke in these patients.

Conclusions: Causality assessment may improve unbiased recognition, management, and voluntary reporting of infrequent adverse effects such as SSRI treatment-related cerebrovascular accident.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Bupropion / therapeutic use
  • Depressive Disorder, Major / drug therapy
  • Dopamine Uptake Inhibitors / therapeutic use
  • Drug Therapy, Combination
  • Dysthymic Disorder / complications
  • Dysthymic Disorder / drug therapy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Obsessive-Compulsive Disorder / complications
  • Obsessive-Compulsive Disorder / drug therapy
  • Paroxetine / adverse effects*
  • Paroxetine / therapeutic use
  • Serotonin Uptake Inhibitors / adverse effects*
  • Serotonin Uptake Inhibitors / therapeutic use
  • Stroke / chemically induced*
  • Trazodone / adverse effects*
  • Trazodone / therapeutic use


  • Dopamine Uptake Inhibitors
  • Serotonin Uptake Inhibitors
  • Bupropion
  • Paroxetine
  • Trazodone