Cambridge Journals Online

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

Abstract

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 α₂-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.