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

Esther Gómez-Gil·Cristóbal Gastó·Marta Carretero·Maribel Díaz-Ricart·Manel Salamero·Ricard Navinés·Ginés Escolar
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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. 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.

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AdultAntidepressive Agents, TricyclicBlood PlateletsMajor Depressive DisorderDrug Administration ScheduleFemaleHumansImipramineMalePlatelet AggregationReceptor, Serotonin, 5-HT2ASerotonin 5-HT2 Receptor AntagonistsClinical TrialJournal ArticleResearch Support, Non-U.S. Gov't

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Esther Gómez-Gil, Cristóbal Gastó, Marta Carretero, Maribel Díaz-Ricart, Manel Salamero, Ricard Navinés, Ginés Escolar. 2004. Decrease of the platelet 5-HT2A receptor function by long-term imipramine treatment in endogenous depression.. https://doi.org/10.1002/hup.583

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