Decrease of the platelet 5-HT2A receptor function by long-term imipramine treatment in endogenous depression

• Published in: Human psychopharmacology Vol. 19; no. 4; pp. 251 - 258
• Main Authors: Gómez-Gil, Esther, Gastó, Cristóbal, Carretero, Marta, Díaz-Ricart, Maribel, Salamero, Manel, Navinés, Ricard, Escolar, Ginés
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.06.2004
• Subjects: 5-HT2A receptor; Adult; antidepressant treatment; Antidepressive Agents, Tricyclic - administration & dosage; Antidepressive Agents, Tricyclic - pharmacology; Antidepressive Agents, Tricyclic - therapeutic use; Blood Platelets - drug effects; Blood Platelets - metabolism; Depressive Disorder, Major - blood; Depressive Disorder, Major - drug therapy; Drug Administration Schedule; endogenous; Female; Humans; imipramine; Imipramine - administration & dosage; Imipramine - pharmacology; Imipramine - therapeutic use; major depression; Male; platelet aggregation; Platelet Aggregation - drug effects; Receptor, Serotonin, 5-HT2A - blood; serotonin; Serotonin 5-HT2 Receptor Antagonists
• ISSN: 0885-6222; 1099-1077
• DOI: 10.1002/hup.583

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. Method 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. Copyright © 2004 John Wiley & Sons, Ltd.