Down-regulation of platelet imidazoline-1-binding sites after bupropion treatment.

An elevation of I1 (imidazoline-1)-binding sites on platelets may be a state marker for depression. Herein, platelet I1 sites were compared in two groups of unipolar depressed patients given different regimens of bupropion treatment: Regimen 1 (n = 13 titrated up to 300 mg/d by week 4 and held constant until week 6); Regimen 2 (n = 15 titrated up to 300 mg/d by week 2, to 450 mg/d by week 6, and held constant until week 8). Platelet I1 sites were quantified by p-[125I]iodoclonidine binding (0.5-15 nM) and displaced by moxonidine under a saturating concentration of norepinephrine to mask alpha2-adrenoceptors. I1 B max values were confirmed to be high at pretreatment in depressed patients (n = 28) compared to healthy control subjects (n = 18; p = 0.02). Highest B max values at pretreatment were found in patients who responded worst to treatment. More than two-thirds of patients recovered from depression (69 and 80% in Regimens 1 and 2, respectively) after treatment. Dose and/or time of exposure to bupropion were relevant variables since (1). only Regimen 2 led to platelet I1 down-regulation and (2). the extent of down-regulation correlated with plasma concentrations of bupropion. The data suggest a dissociation exists between I1 down-regulation and therapeutic response, or else platelet I1 down-regulation lags behind clinical antidepressant response before becoming measurable.