The role of noradrenaline and selective noradrenaline reuptake inhibition in depression.
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.
Brunello
N
N
Department of Pharmaceutical Sciences, University of Modena and Reggio Emilia, Modena, Italy. brunello.nicoletta@unimo.it
Mendlewicz
J
J
Kasper
S
S
Leonard
B
B
Montgomery
S
S
Nelson
J
J
Paykel
E
E
Versiani
M
M
Racagni
G
G
D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003863:Depression / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007099:Imipramine / Q000627:therapeutic use; D008995:Monoamine Oxidase / Q000235:genetics; D009025:Morpholines / Q000627:therapeutic use; D009638:Norepinephrine / Q000378:metabolism* / Q000502:physiology; D000077593:Reboxetine; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D002394:Catechol O-Methyltransferase; D007099:Imipramine; D008995:Monoamine Oxidase; D009025:Morpholines; D009638:Norepinephrine; D000077593:Reboxetine; D011941:Receptors, Adrenergic; D017367:Selective Serotonin Reuptake Inhibitors; D014446:Tyrosine 3-Monooxygenase