title: Serotonin and beyond: therapeutics for major depression.
abstract: The serotonin (5-HT, 5-hydroxytryptamine) system has been implicated in the pathogenesis of major depressive disorder (MDD). The case for its contribution to the therapeutic efficacy of a wide variety of antidepressant treatments is, however, much stronger. All antidepressant strategies have been shown to enhance 5-HT transmission in the brain of laboratory animals. Catecholamines, norepinephrine (NE) and dopamine (DA) can also play a pivotal role in the mechanism of action of certain antidepressant strategies. The enhancement of 5-HT transmission by selective serotonin reuptake inhibitors, which leads to a dampening of the activity of NE and DA neurons, may account in part for the low remission rate achieved with these medications and/or the residuals symptoms after remission is achieved. The functional connectivity between the 5-HT, NE and DA systems can be used to understand the mechanism of action of a wide variety of augmentation strategies in treatment-resistant MDD. Proof-of-concept studies have shown that antidepressant medications with complementary mechanisms of action on monoaminergic systems can double the remission rate achieved in a trial of standard duration. Novel approaches are also being used to treat MDD, which also appear to involve the monoaminergic system(s) to a varying extent.
authors: Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada. pierre.blier@theroyal.ca
authors: Pierre
authors: P
authors: Blier
authors: Mostafa
authors: M
authors: El Mansari
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000473:pathology; D018491:Dopamine Agonists / Q000627:therapeutic use; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D055724:Electrophysiological Phenomena; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009638:Norepinephrine / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D059326:Serotonergic Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D009435:Synaptic Transmission
chemical_list: D000928:Antidepressive Agents; D018491:Dopamine Agonists; D009638:Norepinephrine; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors