Placental Passage of Antidepressant Medications

Hendrick, Victoria; Stowe, Zachary N.; Altshuler, Lori L.; Hwang, Sun; Lee, Emily; Haynes, Desiree

doi:10.1176/appi.ajp.160.5.993

Cited by 330 publications

(252 citation statements)

References 10 publications

Supporting

Mentioning

235

Contrasting

Unclassified

Order By: Relevance

“…25) The involvement of P-gp in the disposition of sertraline and desmethylsertraline is consistent with a recent clinical observation of placental passage of antidepressants. 26) In this study, sertraline and desmethylsertraline exhibited the lowest umbilical cord to maternal serum ratio (0.29) followed by paroxetine (0.54), fluoxetine, (0.64), and citalopram (0.71). 26) These results are in good agreement with a protective role of P-gp in placenta limiting fetal access of these antidepressants, since several of the antidepressants listed (i.e., paroxetine and citalopram) have been identified in previous studies to be substrates of P-gp.…”

Section: Discussionmentioning

confidence: 53%

“…26) In this study, sertraline and desmethylsertraline exhibited the lowest umbilical cord to maternal serum ratio (0.29) followed by paroxetine (0.54), fluoxetine, (0.64), and citalopram (0.71). 26) These results are in good agreement with a protective role of P-gp in placenta limiting fetal access of these antidepressants, since several of the antidepressants listed (i.e., paroxetine and citalopram) have been identified in previous studies to be substrates of P-gp. 3,11,12) This is the first report for a minimal role of P-gp in disposition of bupropion and its three major metabolites.…”

Section: Discussionmentioning

confidence: 53%

See 1 more Smart Citation

Sertraline and Its Metabolite Desmethylsertraline, but not Bupropion or Its Three Major Metabolites, Have High Affinity for P-Glycoprotein

Wang

Zhu

Gibson

et al. 2008

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

The drug transporter protein, P-glycoprotein (P-gp), is a member of the ATP-binding cassette (ABC) superfamily that is widely localized at various human tissues including the apical membranes of the gastrointestinal tract, the biliary canalicular membranes of hepatocytes, the luminal membranes of proximal tubular epithelial cells in the kidney, the testes, the placenta and the luminal membranes of endothelial cells of the blood-brain barrier (BBB). 1,2) As a drug efflux transporter, P-gp plays important role in drug absorption, distribution, and excretion. [3][4][5] Inhibition and induction of P-gp function can result in significant drug-drug interactions.The function of P-gp in BBB can significantly limit the brain uptake of its substrate drugs and affect therapeutic outcomes of central nervous system (CNS) acting drugs. By using the ABCB1a/b Ϫ/Ϫ knockout mice, P-gp has been shown to significantly limit the brain entry of a wide variety of structurally unrelated drugs. [6][7][8][9][10][11][12][13][14] Inhibition of P-gp activity can greatly increase P-gp substrate concentrations in brain and may increase their neurotoxicity. [15][16][17] Because of the importance of P-gp in CNS drug disposition, characterization of the binding affinities of CNS drugs for P-gp has clinical implications.Newer antidepressants, i.e. the selective serotonin reuptake inhibitors (SSRIs) and multi-receptor antidepressants, venlafaxine, mirtazapine, bupropion, and nefazodone have advantages over the classical tricyclic antidepressants in lower frequency to cause unwanted side effects and are extensively used worldwide due to established antidepressants efficacy. 18) However, a substantial number of patients with antidepressant therapy still exhibit treatment resistance despite increasing doses. The reason for this resistance is unknown.Recently, the transport efficacy of most of the antidepressants by P-gp has been studied by using the ABCb1a/b Ϫ/Ϫ mouse or in vitro cell culture models [10][11][12]19) except for two drugs, sertraline and bupropion. In these reports, most of the studied antidepressants (e.g. amitriptyline, nortryptyline, citalopram, and trimipramine) were shown to be substrates of P-glycoprotein. [10][11][12]19) These results suggest that the variable expression of P-gp among patients may be an important source of variability in treatment response for the antidepressants.With availability of human P-gp membranes, we have previously used an ATPase assay method to determine the drug stimulated P-gp-ATPase activity and binding affinity of several antipsychotic drugs. 20) Our results indicated that atypical antipsychotic drugs (AAPs), risperidone, and olanzapine, were effectively transported by P-gp. The findings have been verified by our subsequent in vivo Abcb1a/b gene knockout mouse experiments, 13,14) supporting the ATPase assay to provide reliable information of P-gp substrates' binding affinity. In the present report, we studied the binding affinity of sertraline, desmethylsertraline, bupropion and its three major meta...

show abstract

Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 53%

Sertraline and Its Metabolite Desmethylsertraline, but not Bupropion or Its Three Major Metabolites, Have High Affinity for P-Glycoprotein

Wang

Zhu

Gibson

et al. 2008

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

show abstract

“…When psychological problems arise during pregnancy, an assessment of the medication risks to the mother and the fetus must be made, since antidepressants and benzodiazepines are known to pass across the placenta (Hendrick et al, 2003). Non-pharmacological therapies should be considered as possible choices for pregnant women attempting to avoid medication side-effects.…”

Section: Introductionmentioning

confidence: 99%

Cortisol and anxiety response to a relaxing intervention on pregnant women awaiting amniocentesis

Ventura

Gomes

Carreira

2012

Psychoneuroendocrinology

View full text Add to dashboard Cite

“…In fact, significant SSRI and metabolite concentrations have been detected in both umbilical cord blood and amniotic fluid in women taking these medications during pregnancy. The mean ratios of umbilical cord to maternal serum concentrations ranged from 0.29 to 0.89 (Hostetter et al, 2000;Hendrick et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry

Maciąg

Simpson

Coppinger

et al. 2005

Neuropsychopharmacol

273

275

View full text Add to dashboard Cite

A significant fraction of infants born to mothers taking selective serotonin reuptake inhibitors (SSRIs) during late pregnancy display clear signs of antidepressant withdrawal indicating that these drugs can penetrate fetal brain in utero at biologically significant levels. Previous studies in rodents have demonstrated that early exposure to some antidepressants can result in persistent abnormalities in adult behavior and indices of monoaminergic activity. Here, we show that chronic neonatal (postnatal days 8-21) exposure to citalopram (5 mg/kg, twice daily, s.c.), a potent and highly selective SSRI, results in profound reductions in both the rate-limiting serotonin synthetic enzyme (tryptophan hydroxylase) in dorsal raphe and in serotonin transporter expression in cortex that persist into adulthood. Furthermore, neonatal exposure to citalopram produces selective changes in behavior in adult rats including increased locomotor activity and decreased sexual behavior similar to that previously reported for antidepressants that are nonselective monoamine transport inhibitors. These data indicate that the previously reported neurobehavioral effects of antidepressants are a consequence of their effects on the serotonin transporter. Moreover, these data argue that exposure to SSRIs at an early age can disrupt the normal maturation of the serotonin system and alter serotonin-dependent neuronal processes. It is not known whether this effect of SSRIs is paralleled in humans; however, these data suggest that in utero, exposure to SSRIs may have unforeseen long-term neurobehavioral consequences.

show abstract

Placental Passage of Antidepressant Medications

Cited by 330 publications

References 10 publications

Sertraline and Its Metabolite Desmethylsertraline, but not Bupropion or Its Three Major Metabolites, Have High Affinity for P-Glycoprotein

Sertraline and Its Metabolite Desmethylsertraline, but not Bupropion or Its Three Major Metabolites, Have High Affinity for P-Glycoprotein

Cortisol and anxiety response to a relaxing intervention on pregnant women awaiting amniocentesis

Neonatal Antidepressant Exposure has Lasting Effects on Behavior and Serotonin Circuitry

Contact Info

Product

Resources

About