Stereoselective disposition of fluoxetine and norfluoxetine during pregnancy and breast‐feeding

Kim, John; Riggs, K. Wayne; Misri, Shaila; Kent, Nancy; Oberlander, Tim F.; Grunau, Ruth E.; Fitzgerald, Colleen; Rurak, Dan

doi:10.1111/j.1365-2125.2005.02538.x

Cited by 128 publications

(117 citation statements)

References 31 publications

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“…These include pharmacological factors related to varying half lives, pharmacologically active metabolites 31 and possible competitive inhibition with other medications. 11 Paroxetine's high potency for inhibition of 5HT reuptake and affinity for muscarinic receptors may lead to adverse neonatal outcomes once medication exposure ceases, suggesting a 'discontinuity condition' as proposed by Moses-Kolko.…”

Section: Discussionmentioning

confidence: 99%

Infant serotonin transporter (SLC6A4) promoter genotype is associated with adverse neonatal outcomes after prenatal exposure to serotonin reuptake inhibitor medications

et al. 2007

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Reduced Apgar scores and birth weight, increased risk of respiratory distress, jitteriness and increased tone have been reported in up to 30% of neonates with prenatal exposure to serotonin reuptake inhibitor (SRI) antidepressant medications. In adults, effects of these medications may be related to the genotype for the serotonin transporter (SLC6A4) promoter. In this study we investigated whether SLC6A4 genotype influences the risk for adverse outcomes in neonates with prenatal SRI exposure. Neonatal outcomes including Apgar scores, birth weight, gestational age at birth, symptoms of poor neonatal adaptation and genotype for SLC6A4 were determined in 37 prenatally SRI exposed neonates and compared with 47 nonexposed neonates. Reduced 5 min Apgar scores were observed in exposed neonates and this was moderated by the ss genotype (P < 0.001). Birth weight was lower in exposed ls neonates (P = 0.008). Risk for respiratory symptoms (respiratory distress and rapid breathing) was higher in exposed neonates with the ll genotype compared to non-exposed neonates (P < 0.05) and risk for neuromotor symptoms increased in exposed ss neonates (P < 0.026). These relationships remained when controlling for maternal mood during pregnancy, length of gestational medication exposure and gestational age at birth and cesarean section rate. Prenatal SRI exposure was associated with adverse neonatal outcomes and these effects were moderated by infant SLC6A4 genotype. Relationships between polymorphisms and specific outcomes varied during the neonatal period, suggesting that beyond apparent gene-medication interactions, multiple mechanisms contribute to adverse neonatal outcomes following prenatal SRI exposure.

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Section: Discussionmentioning

confidence: 99%

Infant serotonin transporter (SLC6A4) promoter genotype is associated with adverse neonatal outcomes after prenatal exposure to serotonin reuptake inhibitor medications

et al. 2007

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“…Our understanding of similar neuroanatomical and functional consequences in humans is limited. Because SRIs readily cross the placenta and the blood-brain barrier (19), concerns have been raised about the developmental consequences of altered fetal 5-HT signaling (12,20) or other downstream consequences (21) following prenatal SRI exposure. Importantly, antenatal maternal mood disturbances also have adverse consequences on later cognitive and language development (22)(23)(24) and affect early 5-HT levels (25), leading to confusion about how to distinguish the developmental impact of SRIs from antenatal maternal mood disturbances.…”

mentioning

confidence: 99%

Prenatal exposure to antidepressants and depressed maternal mood alter trajectory of infant speech perception

Weikum

Oberlander

Hensch

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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172

107

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Language acquisition reflects a complex interplay between biology and early experience. Psychotropic medication exposure has been shown to alter neural plasticity and shift sensitive periods in perceptual development. Notably, serotonin reuptake inhibitors (SRIs) are antidepressant agents increasingly prescribed to manage antenatal mood disorders, and depressed maternal mood per se during pregnancy impacts infant behavior, also raising concerns about long-term consequences following such developmental exposure. We studied whether infants' language development is altered by prenatal exposure to SRIs and whether such effects differ from exposure to maternal mood disturbances. Infants from non-SRI-treated mothers with little or no depression (control), depressed but non-SRI-treated (depressed-only), and depressed and treated with an SRI (SRI-exposed) were studied at 36 wk gestation (while still in utero) on a consonant and vowel discrimination task and at 6 and 10 mo of age on a nonnative speech and visual language discrimination task. Whereas the control infants responded as expected (success at 6 mo and failure at 10 mo) the SRI-exposed infants failed to discriminate the language differences at either age and the depressed-only infants succeeded at 10 mo instead of 6 mo. Fetuses at 36 wk gestation in the control condition performed as expected, with a response on vowel but not consonant discrimination, whereas the SRI-exposed fetuses showed accelerated perceptual development by discriminating both vowels and consonants. Thus, prenatal depressed maternal mood and SRI exposure were found to shift developmental milestones bidirectionally on infant speech perception tasks.L anguage, our most quintessential human characteristic, involves a complex interplay between biology and experience. At birth, infants possess an initial preparedness for language and a developmental readiness that supports learning any of the world's languages (1-3), yet also already show privileged processing to the native language from prenatal listening experience (4-6). During the following weeks and months of life, infants become progressively attuned to the properties of their native language, including its rhythmical and segmental (e.g., consonant) information (reviewed in refs. 7 and 8). The high degree of regularity in the timing of sequential tuning to properties of the native language suggests a series of critical or sensitive periods, i.e., points in development when the system is maximally influenced by input.The timing of onset of these sensitive periods seems to be maturationally constrained. Infants born 3 mo preterm attune to the phonetic properties (9) of their native language at the same gestational age as full-term infants, not according to the number of months of postnatal listening experience. Such maturational constraints can protect development: ensuring the optimal consecutive stabilization of the perceptual components that contribute in a step-wise fashion to language acquisition (10). However, it is known from research i...

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“…There is a stereoselective disposition of fluoxetine and norfluoxetine resulting in increased concentrations of the biologically active enantiomers in the infant compared with the mother [31]. In a study including eleven infants exposed to fluoxetine through breast milk it was reported a variation in platelet serotonin levels in one infant but no adverse effects were observed [32].…”

Section: Fluoxetinementioning

confidence: 99%

Use of Antidepressants to Treat Postpartum Depression, During Breast Feeding

Fonseca¹,

Leal²

2014

J Depress Anxiety

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Postpartum depression affects approximately 14.5% of women and it can affect both mother and infant. Therefore, rapid attention and treatment are imperative. The pharmacological approach often represents one of the most realistic options of treatment. However, women may be reluctant to take antidepressants because of the fear of adverse effects for the infant, since that most drugs pass into breast milk. The use of pharmacotherapy has not been extensively documented in this population. The objective of this review is to evaluate the risk benefit of using antidepressants during breastfeeding to treat postpartum depression.An electronic search was performed by using PubMed database, from January 2001 through December 2010. The search was limited to articles in the English language and to articles that relate human's research. Manual searches of bibliographies were also conducted to identify additional pertinent studies.The use of antidepressants that do not appear in infants' plasma, for which use during breastfeeding is better documented and at standard therapeutic doses is recommended, such as sertraline and paroxetine. Fluoxetine has a long half-life which can lead to a long infant exposition through breast milk and citalopram can cause adverse effects in infants exposed through breast milk. Therefore, citalopram and fluoxetine should not be used as first-line treatments. More information is needed about the use of the other antidepressants referred in this study.This study aims to emphasize the importance of postpartum depression treatment, always considering its repercussions for the breastfed infants. Studies are needed with larger samples to properly evaluate the short and long-term effects of antidepressants on infants exposed through breast milk, so that clinicians can create standard decisions regarding the treatment of postpartum depression, without putting infants at risk.

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Stereoselective disposition of fluoxetine and norfluoxetine during pregnancy and breast‐feeding

Cited by 128 publications

References 31 publications

Infant serotonin transporter (SLC6A4) promoter genotype is associated with adverse neonatal outcomes after prenatal exposure to serotonin reuptake inhibitor medications

Infant serotonin transporter (SLC6A4) promoter genotype is associated with adverse neonatal outcomes after prenatal exposure to serotonin reuptake inhibitor medications

Prenatal exposure to antidepressants and depressed maternal mood alter trajectory of infant speech perception

Use of Antidepressants to Treat Postpartum Depression, During Breast Feeding

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