Additional dopamine reuptake inhibition prevents vigilance decrement induced by serotonergic reuptake inhibition in man.

J.A.J. Schmitt*, J.G. Ramaekers, M. Kruizinga, S.H. Teunisse, M.P.J. van Boxtel, E.F.P.M. Vuurman, W.J. Riedel

*Corresponding author for this work

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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.
Original languageEnglish
Pages (from-to)207-214
JournalJournal of Psychopharmacology
Issue number3
Publication statusPublished - 1 Jan 2002


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