title: Decrease of the platelet 5-HT2A receptor function by long-term imipramine treatment in endogenous depression.
abstract: BACKGROUND
  Animal studies have found that many antidepressants induce decreases in both the density and the functional activity of the serotonin 2A (5-HT2A) receptor subtype. However, the extrapolation of findings to humans has been inconclusive. A physiological platelet response mediated by this receptor, the serotonin-amplified platelet aggregation, was measured to study whether long-term antidepressant treatment induces changes in 5-HT2A receptor functioning in endogenous depressed patients.
  
  
  METHODS
  The percentage of serotonin-amplified platelet aggregation to adenosine diphosphate (ADP) was studied in 15 untreated patients with major depressive disorder (DSM-IV) with endogenous features (Newcastle scale). This index was used as an indirect measurement of the functional status of platelet 5-HT2A receptors. Aggregation studies were repeated once remission of the symptoms was achieved during treatment with imipramine (150-300 mg/day). A group of 15 concurrent normal subjects was used as a control.
  
  
  RESULTS
  A statistically significant decrease (p = 0.038) in the percentage of serotonin-amplified platelet aggregation to ADP was observed when remission was achieved (after 145 +/- 27 days).
  
  
  CONCLUSIONS
  The results showed a decrease in a platelet functional response mediated by 5-HT2A receptors following effective imipramine treatment, suggesting that desensitization or down-regulation of the 5-HT2A receptor function could be linked to the therapeutic effect of some antidepressants. The data also support the use of platelet aggregometry as a surrogate measurement of antidepressant action, particularly in intra-subject designs.
authors.affiliation: Instituto Clínic de Psiquiatría y Psicología, Hospital Clinic, Villarroel, Barcelona, Spain. esgomez@clinic.ub.es
authors.forename: Esther
authors.initials: E
authors.lastname: Gómez-Gil
authors.forename: Cristóbal
authors.initials: C
authors.lastname: Gastó
authors.forename: Marta
authors.initials: M
authors.lastname: Carretero
authors.forename: Maribel
authors.initials: M
authors.lastname: Díaz-Ricart
authors.forename: Manel
authors.initials: M
authors.lastname: Salamero
authors.forename: Ricard
authors.initials: R
authors.lastname: Navinés
authors.forename: Ginés
authors.initials: G
authors.lastname: Escolar
mesh_terms: D000328:Adult; D000929:Antidepressive Agents, Tricyclic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007099:Imipramine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D044402:Receptor, Serotonin, 5-HT2A / Q000097:blood; D058830:Serotonin 5-HT2 Receptor Antagonists
chemical_list: D000929:Antidepressive Agents, Tricyclic; D044402:Receptor, Serotonin, 5-HT2A; D058830:Serotonin 5-HT2 Receptor Antagonists; D007099:Imipramine