Safety concerns associated with the use of serotonin reuptake inhibitors and other serotonergic/noradrenergic antidepressants during pregnancy: A review

Tuccori, Marco; Testi, Arianna; Antonioli, Luca; Fornai, Matteo; Montagnani, Sabrina; Ghisu, Narcisa; Colucci, Rocchina; Corona, Tiberio; Blandizzi, Corrado; Tacca, M. Del

doi:10.1016/j.clinthera.2009.07.009

Cited by 88 publications

(63 citation statements)

References 110 publications

(37 reference statements)

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“…As the regulatory network involved in the specific expression of Bapx1 in vertebrates is conserved (Newman et al, 1997;Miller et al, 2003;Tucker et al, 2004), it may be hypothesized that 5-HT2B signaling controls Bapx1 expression in mammalian embryos as well. This aspect, to be verified and further to SSRIs such as persistent pulmonary hypertension, cardiac defects and spontaneous abortion (Oberlander et al, 2009;Tuccori et al, 2009;Bellissima et al, 2012). An association between congenital heart defects and the use of SSRIs in pregnancy has been demonstrated (Sadler, 2011) and these findings are in line with animal model studies showing a key role of 5-HT2B receptor signaling in heart development (Gaspar et al, 2003).…”

Section: -Ht2b Signaling and Craniofacial Morphogenesis/jaw Joint Fosupporting

confidence: 74%

Unraveling new roles for serotonin receptor 2B in development: key findings from Xenopus

Ori¹,

Lucchini²,

Marras³

et al. 2013

Int. J. Dev. Biol.

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The serotonin receptor 5-HT2B has been shown to be critically important during embryogenesis as the knockout of this gene in mice causes heart defects and embryonic lethality that impairs further analyses on other embryonic cell and tissue types. In the present review, we highlight how the use of Xenopus laevis, an alternative vertebrate model suitable for gene loss and gain of function analyses, has contributed to our understanding of the role of 5-HT2B signaling during development. In vivo studies showed that 5-HT2B signaling is not only required for heart development, but that it also has a crucial role in ocular and craniofacial morphogenesis, being involved in shaping the first branchial arch and the jaw joint, in retinogenesis and possibly in periocular mesenchyme development. These findings may be relevant for our understanding of congenital defects including human birth malformations. In addition, 5-HT2B appears to be required for the therapeutic actions of selective serotonin reuptake inhibitors commonly prescribed as antidepressant drugs to pregnant and lactating women. We discuss how the understanding of the molecular basis of serotonin signaling in a suitable animal embryogenesis model may open new lines of investigations and therapies in humans. KEY WORDS: 5-HT2B, neural crest cell, eye, craniofacial morphogenesis, SSRISerotonin, an ancient molecule with unsuspected and still unveiled functions Serotonin (5-hydroxytryptamine, 5-HT) is a phylogenetically ancient monoamine that fulfills a broad role in the control of many vital functions including the control of gastrointestinal motility and secretion, cardiovascular regulation, hemostatic processes, the regulation of circadian rhythms, the control of the sleep-wake cycle, memory and learning, perception of pain, appetite and sexual behavior (reviewed by Berger et al., 2009). The broad action of the serotonin signaling system has attracted the interest of researchers in various fields of biology and molecular medicine, spanning from developmental biology, neurobiology to molecular psychiatry. 5-HT is best known for its role in the nervous system where it is one of the neurotransmitters mainly involved in the etiology of various human psychiatric disorders, including anxiety, depression, obsessive-compulsive disorders, schizophrenia, pain and migraine. Accordingly, many substances that interfere with the serotonergic system are commonly used as therapeutic agents. Selective serotonin reuptake inhibitors (SSRIs) are, in fact, the most frequently prescribed drugs for the treatment of depression Int. J. Dev. Biol. 57: 707-714 (2013) Abbreviations used in this paper: 5-HT, serotonin; 5-HTT, serotonin transporter; CNS, central nervous system; CMZ, ciliary marginal zone; Edn1, endothelin 1; GCL, gaglion cell layer; INL, inner nuclear layer; NCCs, neural crest cells; POM, periocular mesenchyme; SSRI, selective serotonin reuptake inhibitors; Tph2, tryptophan hydroxylase 2.and anxiety-related disorders (Berton and Nestler, 2006). These drugs inhibit...

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Section: -Ht2b Signaling and Craniofacial Morphogenesis/jaw Joint Fosupporting

confidence: 74%

Unraveling new roles for serotonin receptor 2B in development: key findings from Xenopus

Ori¹,

Lucchini²,

Marras³

et al. 2013

Int. J. Dev. Biol.

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“…The use of concomitant medications for general medical conditions may influence the choice of medication. Pregnancy and lactation require careful consideration of the risk-benefit ratio of using medication [23]. The use of β-blockers (see below) is contraindicated in certain medical disorders.…”

Section: Discussionmentioning

confidence: 99%

A 2010 Evidence-Based Algorithm for the Pharmacotherapy of Social Anxiety Disorder

Stein

Baldwin

Bandelow

et al. 2010

Curr Psychiatry Rep

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A growing evidence base on the management of social anxiety disorder has yielded many meta-analyses and guidelines on the pharmacotherapy of this clinically important condition. We aimed to update a pharmacotherapy algorithm for the treatment of social anxiety disorder that was developed to be concise and user friendly and that was addressed to the primary care practitioner in particular. The updated algorithm attempts to summarize succinctly the recent literature in this area, as well as to include the views of an international panel of experts with diverse experience. The algorithm comprises eight sequential steps, beginning with those focused on diagnosis and initiating treatment and ending with the management of the treatment-refractory patient.

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“…Numerous reviews cite the apparent safety of antidepressants during pregnancy (Koren et al, 1998;Kulin et al, 1998a;Davanzo et al, 2011). Others point out that the risk of administering these medications during pregnancy is still uncertain (Tuccori et al, 2009;Ellfolk and Malm, 2010). The issue sparks intense debate, and some point out that the risk is too great and psychotherapy should supplant antidepressants (Campagne, 2007), although this is contested by others who conduct large center studies investigating these issues (Campagne, 2008;Einarson and Eberhard-Gran, 2013;Einarson, 2009).…”

Section: Summary Of Human Exposure Studiesmentioning

confidence: 99%

Prenatal Antidepressant Exposure: Clinical and Preclinical Findings

2014

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Safety concerns associated with the use of serotonin reuptake inhibitors and other serotonergic/noradrenergic antidepressants during pregnancy: A review

Cited by 88 publications

References 110 publications

Unraveling new roles for serotonin receptor 2B in development: key findings from Xenopus

Unraveling new roles for serotonin receptor 2B in development: key findings from Xenopus

A 2010 Evidence-Based Algorithm for the Pharmacotherapy of Social Anxiety Disorder

Prenatal Antidepressant Exposure: Clinical and Preclinical Findings

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