Effect of fluvoxamine on platelet 5-HT2A receptors as studied by [H-3]lysergic acid diethylamide ([H-3]LSD) binding in healthy volunteers

Alterations in platelet 5-HT2A receptor characteristics have been reported in major depression as well as in other psychiatric diseases, and some effort has been made to utilize platelet 5-HT2A receptor status as a biological correlate to antidepressant drug response. In order to investigate whether treatment with a selective serotonin reuptake inhibitor affects platelet 5-HT2A receptors, we have studied platelet [H-3]lysergic acid diethylamide ([H-3]LSD) binding in healthy subjects treated with fluvoxamine in increasing dosage once weekly for 4 weeks. After 1 week of fluvoxamine treatment (25 mg/day), both B-max and K-d were significantly lower than before the start of the treatment (19.9 versus 25.5 fmol/mg protein, P = 0.005 for B-max; 0.45 versus 0.93 nM, P = 0.006 for K-d) B-max returned to baseline during week 2, whereas K-d was lower than the baseline value throughout the treatment period. After discontinuation of fluvoxamine treatment, there was a significant increase in K-d (0.50 nM before discontinuation vs. 1.14 nM after discontinuation; P = 0.001), but not in B-max. The study demonstrates that fluvoxamine affects platelet 5-HT2A receptor status irrespective of underlying psychiatric disease, and that this effect is evident already after 1 week at a subtherapeutic fluvoxamine dose.