Idazoxan: A Selective α2-Antagonist and Effective Sustained Antidepressant in Two Bipolar Depressed Patients

To the Editor.—  We report on the therapeutic and biochemical effects of short- and long-term administration of idazoxan, a selective α₂-administration and a putative antidepressant, in three patients with the diagnosis of depression and a history of poor response to standard treatments. The down regulation of central β-receptors in response to increased synaptic norepinephrine (NE) levels has consistently been demonstrated after tricyclic antidepressant¹ as well as other effective treatments for depression.^2,3 In addition, α₂-adrenergic receptors have been shown to down regulate in response to at least some antidepressants.^4,5 Furthermore, blockade of α-receptors can accelerate the down regulation of β-receptors by tricyclic antidepressants in rats,⁶ probably by enhancing intrasynaptic NE through the blockade of prejunctional α₂-receptors that normally mediate feedback inhibition of NE release.⁷ In human studies, however, the addition of yohimbine therapy to patients who had failed to respond