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Disturbed development of the enteric nervous system after in utero exposure of selective serotonin re-uptake inhibitors and tricyclic antidepressants. Part 2: Testing the hypotheses.

Abstract：

AIMS:Antidepressant use has increased in the last decade. Several studies have suggested a possible association between maternal antidepressant use and teratogenic effects. METHODS:The pharmacy prescription database IADB.nl was used for a cohort study in which laxative and antidiarrhoeal medication use in children after in utero exposure to antidepressants (TCA, SSRI, fluoxetine or paroxetine exposed) was compared with no antidepressant exposure. Laxatives and antidiarrhoeal medication use were applied as a proxy for constipation and diarrhoea respectively, which may be associated with disturbed enteric nervous system (ENS) development. RESULTS:Children exposed in utero to SSRIs (mainly fluoxetine and paroxetine) in the second and third trimester or to TCAs in the first trimester, more often received laxatives. Combined exposure to TCAs and SSRIs in pregnancy was associated with a 10-fold increase in laxative use. In utero exposure to SSRIs is not associated with antidiarrhoeal medication use compared with non-exposed children. In contrast, antidiarrhoeal medication use was significantly higher in children exposed to TCAs anytime in pregnancy. CONCLUSIONS:The increased laxative use after second and third trimester exposure to SSRIs might be explained through the inhibitory effect of the serotonin re-uptake transporter (SERT) and because of selectivity for the 5-HT(2B) receptor which affects the ENS. TCA exposure during the first trimester leads to increased laxative use probably through inhibition of the norepinephrine transporter (NET). Exposure of TCAs anytime in pregnancy leads to increase diarrhoeal use possibly through down-regulation of α₂-adrenoceptors or up-regulation of the pore forming α(1c) subunit.

journal_name

Br J Clin Pharmacol

journal_title

British journal of clinical pharmacology

authors

Nijenhuis CM,ter Horst PG,van Rein N,Wilffert B,de Jong-van den Berg LT

doi

10.1111/j.1365-2125.2011.04081.x

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

126-34

issue

eissn

0306-5251

issn

1365-2125

journal_volume

pub_type

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Disturbed development of the enteric nervous system after in utero exposure of selective serotonin re-uptake inhibitors and tricyclic antidepressants. Part 2: Testing the hypotheses.