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.

Effects of sertraline on depressive symptoms and attentional and executive functions in major depression

“…Siepmann's et al's [2003] research with normal volunteers showed that sertraline does not have either a positive or a negative ef fect on cognition, and so argues against this possibility. Studies by Furlan's et al [2001] and Schmitt et al [2002] also suggested that sertraline improves depression-related cognition.…”

“…Tricyclic antidepressants, having very potent antihistaminic and anticholinergic effects, can interfere with cognitive and psychomotor functions [Riedel and van Praag, 1995]. Sertraline, however, has been shown to have no adverse effect on cognition in healthy volunteers [Furlan et al, 2001;Schmitt et al, 2002]. As our study shows an adverse effect on the executive functions of inhibition in depressed subjects, an improvement in these functions during sertraline treatment was probably related to the reduction in blood flow and cerebral glucose metabolism in the frontal regions in the depressive state [Baxter et al, 1989, Bench et al, 1992, Martinot et al, 1990 and to the increase in cerebral glucose metabolism in the frontal regions after 10 weeks of sertraline treatment [Buchsbaum et al, 1997].…”

Pronounced Cognitive Deficits Following an Intravenous L-Tryptophan Challenge in First-Degree Relatives of Bipolar Patients Compared to Healthy Controls

“…Direct effects of 5-HT on vigilance and the conversion of Trp to melatonin may explain the sedative effects of Trp (Cooper et al, 1991;Schmitt et al, 2002). Correlation analyses showed sedation to be positively associated with impaired memory performance.…”

Psychomotor Changes in Major Depressive Disorder during Sertraline Treatment

“…As an SSRI, sertraline possesses, besides its serotonergic activity, a relatively high affinity for the human dopamine transporter and may also facilitate dopaminergic neurotransmission. Despite its dopaminergic properties being 100-fold lower than its serotonin reuptake blocking properties, it should be mentioned that this dopaminergic activity clearly distinguishes sertraline from all other SSRIs that do not have such activity [14][15][16]31] . Note also that the potency of sertraline for dopamine reuptake blockade is reported to be about one third that of d-amphetamine [14,16] .…”