title: The other face of depression, reduced positive affect: the role of catecholamines in causation and cure.
abstract: Despite significant advances in pharmacologic therapy of depression over the past two decades, a substantial proportion of patients fail to respond or experience only partial response to serotonin re-uptake inhibitor antidepressants, resulting in chronic functional impairment. There appears to be a pattern of symptoms that are inadequately addressed by serotonergic antidepressants - loss of pleasure, loss of interest, fatigue and loss of energy. These symptoms are key to the maintenance of drive and motivation. Although these symptoms are variously defined, they are consistent with the concept of ;decreased positive affect'. Positive affect subsumes a broad range of positive mood states, including feelings of happiness (joy), interest, energy, enthusiasm, alertness and self-confidence. Although preliminary, there is evidence to suggest that antidepressants that enhance noradrenergic and dopaminergic activity may afford a therapeutic advantage over serotonergic antidepressants in the treatment of symptoms associated with a reduction in positive affect. Dopaminergic and noradrenergic agents, including the dual acting norepinephrine and dopamine re-uptake inhibitors, have demonstrated antidepressant activity in the absence of serotonergic function, showing similar efficacy to both tricyclic and serotonin re-uptake inhibitor antidepressants. Moreover, the norepinephrine and dopamine re-uptake inhibitor bupropion has been shown to significantly improve symptoms of energy, pleasure and interest in patients with depression with predominant baseline symptoms of decreased pleasure, interest and energy. Focusing treatment on the predominant or driving symptomatology for an individual patient with major depression could potentially improve rates of response and remission.
authors.affiliation: University of Bristol Psychopharmacology Unit, Bristol, UK. david.j.nutt@bristol.ac.uk
authors.forename: David
authors.initials: D
authors.lastname: Nutt
authors.forename: Koen
authors.initials: K
authors.lastname: Demyttenaere
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Janka
authors.forename: Trond
authors.initials: T
authors.lastname: Aarre
authors.forename: Michel
authors.initials: M
authors.lastname: Bourin
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Canonico
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Carrasco
authors.forename: Steven
authors.initials: S
authors.lastname: Stahl
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000627:therapeutic use; D000339:Affect / Q000187:drug effects*; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002395:Catecholamines / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use; D006801:Humans; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D009638:Norepinephrine / Q000378:metabolism; D018579:Patient Selection; D012074:Remission Induction; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D002395:Catecholamines; D004298:Dopamine; D018765:Dopamine Uptake Inhibitors; D014179:Neurotransmitter Uptake Inhibitors; D009638:Norepinephrine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors