title: Additional dopamine reuptake inhibition attenuates vigilance impairment induced by serotonin reuptake inhibition in man.
abstract: There is evidence for a specific impairment of human vigilance following enhancement of serotonergic activity by antidepressant drugs. In the present study, we investigated the putative role of serotonergic-dopaminergic interactions in diminished vigilance by comparing the attentional effects of sertraline, a selective serotonin reuptake inhibitor (SSRI) with additional mild dopamine stimulating effects, with those of paroxetine, a SSRI without dopamine activity, using a placebo-controlled, double-blind, three-way cross-over design. Twenty-one (of 24) healthy middle-aged subjects completed the three treatment periods of 2 weeks in which sertraline (50 mg, days 1-7; 100 mg, days 8-14), paroxetine (20 mg, days 1-7; 40 mg, days 8-14) and placebo were administered. Vigilance (Mackworth Clock Test), selective (Stroop, Dichotic Listening) and divided attention (Dichotic Listening) were assessed at baseline and on days 7 and 14 of each treatment period. Selective and divided attention were unaffected by SSRI treatment. Subchronic administration of paroxetine impaired vigilance performance at each investigated dose. Sertraline did not produce a significant decline in vigilance performance, presumably due to its concomitant effects on dopamine activity, counteracting the negative effects of serotonin on dopamine neurotransmission. It is concluded that a serotonergically mediated reduction of dopamine activity plays an important role in the reduction of human vigilance following SSRI administration.
authors.affiliation: Department of Psychiatry and Neuropsychology, Brain and Behaviour Institute, Universiteit Maastricht, The Netherlands. j.schmitt@np.unimaas.nl
authors.forename: Jeroen A J
authors.initials: JA
authors.lastname: Schmitt
authors.forename: Johannes G
authors.initials: JG
authors.lastname: Ramaekers
authors.forename: Monique J
authors.initials: MJ
authors.lastname: Kruizinga
authors.forename: Martin P J
authors.initials: MP
authors.lastname: van Boxtel
authors.forename: Eric F P M
authors.initials: EF
authors.lastname: Vuurman
authors.forename: Wim J
authors.initials: WJ
authors.lastname: Riedel
mesh_terms: D000328:Adult; D001288:Attention / Q000187:drug effects*; D018592:Cross-Over Studies; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D018765:Dopamine Uptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D017374:Paroxetine / Q000009:adverse effects / Q000627:therapeutic use*; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D020280:Sertraline / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D018765:Dopamine Uptake Inhibitors; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline