The role of noradrenaline and selective noradrenaline reuptake inhibition in depression

Eur Neuropsychopharmacol. 2002 Oct;12(5):461-75. doi: 10.1016/s0924-977x(02)00057-3.


Depression is a common disorder that impacts on all aspects of a person's life. For the past 10 years, clinicians have focused on serotonin in their treatment of depression. This is largely due to the growing acceptance of the efficacy and safety of the selective serotonin reuptake inhibitors (SSRIs) in comparison with older tricyclic antidepressants (TCAs). However, evidence for a role of noradrenaline in depression has been accumulating for some time, beginning with the discovery that drugs which either caused or alleviated depression acted to alter noradrenaline metabolism. Until recently, the role of noradrenaline in depression was predicted from clinical experience with noradrenergic TCAs (desipramine, nortriptyline and protriptyline) and selective serotonin and noradrenaline reuptake inhibitors (venlafaxine, milnacipran). The licensing of reboxetine, a selective noradrenaline reuptake inhibitor now allows the role of noradrenaline in depression to be investigated directly. This review presents key data from the literature that support a role for noradrenaline in depression taking into account neurophysiology, psychopharmacology and clinical trial data.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adrenergic Uptake Inhibitors / therapeutic use
  • Animals
  • Antidepressive Agents / therapeutic use
  • Catechol O-Methyltransferase / genetics
  • Depression / drug therapy*
  • Depression / genetics
  • Depression / metabolism
  • Humans
  • Imipramine / therapeutic use
  • Monoamine Oxidase / genetics
  • Morpholines / therapeutic use
  • Norepinephrine / metabolism*
  • Norepinephrine / physiology
  • Reboxetine
  • Receptors, Adrenergic / drug effects
  • Receptors, Adrenergic / metabolism
  • Serotonin Uptake Inhibitors / therapeutic use*
  • Treatment Outcome
  • Tyrosine 3-Monooxygenase / genetics


  • Adrenergic Uptake Inhibitors
  • Antidepressive Agents
  • Morpholines
  • Receptors, Adrenergic
  • Serotonin Uptake Inhibitors
  • Reboxetine
  • Tyrosine 3-Monooxygenase
  • Monoamine Oxidase
  • Catechol O-Methyltransferase
  • Imipramine
  • Norepinephrine