Additional dopamine reuptake inhibition attenuates vigilance impairment induced by serotonin reuptake inhibition in man.
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.
Schmitt
Jeroen A J
JA
Department of Psychiatry and Neuropsychology, Brain and Behaviour Institute, Universiteit Maastricht, The Netherlands. j.schmitt@np.unimaas.nl
Ramaekers
Johannes G
JG
Kruizinga
Monique J
MJ
van Boxtel
Martin P J
MP
Vuurman
Eric F P M
EF
Riedel
Wim J
WJ
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*
D018765:Dopamine Uptake Inhibitors; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline