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Decrease of the platelet 5‐HT 2A receptor function by long‐term imipramine treatment in endogenous depression
Author(s) -
GómezGil Esther,
Gastó Cristóbal,
Carretero Marta,
DíazRicart Maribel,
Salamero Manel,
Navinés Ricard,
Escolar Ginés
Publication year - 2004
Publication title -
human psychopharmacology: clinical and experimental
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.461
H-Index - 78
eISSN - 1099-1077
pISSN - 0885-6222
DOI - 10.1002/hup.583
Subject(s) - imipramine , serotonin , medicine , platelet , antidepressant , receptor , endogeny , endocrinology , 5 ht receptor , adenosine diphosphate , endogenous depression , pharmacology , chemistry , platelet aggregation , hippocampus , alternative medicine , pathology
Background Animal studies have found that many antidepressants induce decreases in both the density and the functional activity of the serotonin 2A (5‐HT 2A ) 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‐HT 2A 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‐HT 2A 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‐HT 2A receptors following effective imipramine treatment, suggesting that desensitization or down‐regulation of the 5‐HT 2A 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.