Predicting response: noradrenaline reuptake inhibition

For the past decade, the role of noradrenaline in depression has been somew hat neglected in favour of serotonin, This is largely because of the advent of the selective serotonin reuptake inhibitors, which have facilitated cli nical and experimental observation of the roles of serotonin, Until now no such tools have been available to study the noradrenergic system. However, the recent development of reboxetine, the first selective noradrenaline reu ptake inhibitor, has allowed clinical investigation of the role of the nora drenergic system in different aspects of depressive disorders. In clinical trials, the use of reboxetine has shown that selective noradrenaline reupta ke inhibition is an effective approach to alleviating depression. It is mor e effective than placebo and at least as effective as desipramine, imiprami ne and fluoxetine in the short term. In addition, its efficacy is maintaine d in patients with severe depression and in those receiving long-term maint enance treatment. Reboxetine is very well tolerated, as predicted from its pharmacological profile, having fewer anticholinergic side-effects than imi pramine or desipramine. Compared with fluoxetine, patients treated with reb oxetine experienced less nausea and sexual dysfunction, adverse events that are common among those taking selective serotonin reuptake inhibitors. Adv erse events predicted by the neuroanatomy of the noradrenergic system, such as tremor and cardiovascular effects, occurred less frequently than expect ed. Clinical experience with reboxetine challenges our current knowledge of the role of noradrenaline in depression and questions existing evidence ba sed on studies with noradrenergic tricyclic antidepressants, Selective nora drenaline reuptake inhibition, as exemplified by reboxetine, therefore offe rs a significant improvement in antidepressant pharmacotherapy, and an oppo rtunity to increase our understanding of the role of noradrenaline in depre ssion. Int Clin Psychopharmacol 14 (suppl 1):S21-S26 (C) 1999 Lippincott Wi lliams & Wilkins.