Decreased serotonin content and reduced agonist-induced aggregation in platelets of patients chronically medicated with SSRI drugs

J Affect Disord. 2012 Jan;136(1-2):99-103. doi: 10.1016/j.jad.2011.08.013. Epub 2011 Sep 4.


Background: Chronic treatment with selective serotonin reuptake inhibitors (SSRIs) reduces the risk and severity of cardiovascular diseases. SSRIs block the serotonin transporter, thereby inhibiting serotonin (5-HT) uptake into presynaptic neurons as well as into platelets where 5-HT is stored in dense granules. When 5-HT is released in response to agonists it enhances platelet aggregation induced by injury-related signals. Chronic administration of SSRIs may thus reduce platelet aggregability secondary to depletion of platelets' serotonin stores.

Methods: The study included ten DSM-IV-TR major depression (MDD) and four obsessive compulsive disorder (OCD) patients and fourteen healthy untreated age- and sex-matched controls. The patients were chronically medicated (6-108 months) with various SSRIs. Platelet serotonin content was assessed in fresh samples of platelet rich plasma (PRP) using radioimmunoassay. ADP, collagen, arachidonic acid and epinephrine were used as inducers of platelet aggregation measured in PRP by turbometric method in a microplate reader.

Results: Lower platelet serotonin content (66%; p<0.05) and lower ADP, collagen or epinephrine-induced platelet aggregation (10-52%; p<0.05) were detected in PRP of SSRI-medicated patients, while no such effect was obtained with arachidonic acid.

Limitations: The small sample size and the co-treatment with non-SSRI drugs such as benzodiazepines.

Conclusion: Patients chronically medicated with SSRIs exhibit lower platelet 5-HT content and reduced platelet aggregation induced by ADP, collagen and epinephrine, but not by arachidonic acid. Our observations may explain the increased bleeding risk associated with chronic SSRI treatment as well as the reported beneficial effect of SSRIs in prevention of recurrent myocardial infarction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use
  • Blood Platelets / chemistry*
  • Blood Platelets / drug effects
  • Depressive Disorder, Major / drug therapy*
  • Female
  • Humans
  • Male
  • Obsessive-Compulsive Disorder / drug therapy*
  • Platelet Aggregation / drug effects*
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Serotonin / analysis*
  • Serotonin / blood


  • Antidepressive Agents
  • Serotonin Uptake Inhibitors
  • Serotonin