title: Dual monoamine modulation for improved treatment of major depressive disorder.
abstract: The worldwide scope of depressive illness and lack of fully effective pharmacotherapy mandates significant improvements in treatment paradigms. Current antidepressant medications remain limited by poor efficacy, slow onset of action, and untoward side effects. While the introduction of serotoninspecific reuptake inhibitors (SSRIs) offered significant improvements in tolerability, no improvements in efficacy or speed of onset have been made relative to the traditional and poorly tolerated tricyclic antidepressants (TCA). The dominant efforts toward improving antidepressant medications are guided by cumulative evidence from neurochemical and clinical studies supporting the therapeutic potential of enhancing monoamine function in depression. A number of novel antidepressant drugs, including mirtazapine, milnacipran, venlafaxine, and duloxetine have been developed based on their interaction with both 5-HT and NE. Current clinical evidence suggests that these new agents may offer improved efficacy and/or faster onset of action compared with SSRIs and an improved side effect profile compared with TCAs. Potential neurobiological substrates mediating the enhanced antidepressant activity of dual reuptake inhibitors are discussed.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA. tran_pierre_v@lilly.com
authors.forename: Pierre V
authors.initials: PV
authors.lastname: Tran
authors.forename: Frank P
authors.initials: FP
authors.lastname: Bymaster
authors.forename: Robert K
authors.initials: RK
authors.lastname: McNamara
authors.forename: William Z
authors.initials: WZ
authors.lastname: Potter
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use; D000818:Animals; D015306:Biogenic Monoamines / Q000502:physiology*; D001923:Brain Chemistry / Q000187:drug effects; D002986:Clinical Trials as Topic; D003865:Major Depressive Disorder / Q000188:drug therapy*; D006801:Humans; D014179:Neurotransmitter Uptake Inhibitors / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use
chemical_list: D018759:Adrenergic Uptake Inhibitors; D015306:Biogenic Monoamines; D014179:Neurotransmitter Uptake Inhibitors; D017367:Selective Serotonin Reuptake Inhibitors