PIH3 Pregnancy Outcomes Folowing Exposure to Serotonin Reuptake Inhibitors: A Meta-Analysis

Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Reproductive Toxicology (Impact Factor: 3.23). 12/2006; 22(4):571-5. DOI: 10.1016/j.reprotox.2006.03.019
Source: PubMed


Serotonin reuptake inhibitors (SRIs) are extensively used in management of clinical depression. Reports vary about the risk of these drugs during pregnancy. To determine the risk of exposure to SRIs, we pooled data from multiple clinical studies that investigated obstetrical outcomes in women exposed to this group of drugs during pregnancy. Studies were identified by search of PUBMED, OVID, and SCOPUS databases and the data were derived from 1990 to 2005 (August). Types of outcome investigated were spontaneous abortion, major malformations, cardiovascular malformations, and minor malformations. The criteria for inclusion of studies in this meta-analysis were exposure of women to any therapeutic dosage of SRI (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) during pregnancy. Our results find that SRIs do not increase the risk of major, cardiovascular and minor malformations but do increase the risk of spontaneous abortion significantly.

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Available from: Mohammad Abdollahi, Dec 31, 2014
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    • "among antidepressant-exposed pregnancies versus matched control pregnancies.174 A subsequent meta-analysis of nine nonheterogeneous studies (five of which reported on rates of spontaneous abortion in 1,900 exposed pregnancies) by Rahimi et al reported a summary OR of 1.7 (95% CI 1.28–2.24).109 The majority of reviewed studies did not adequately address important confounding factors, including history of miscarriage, rates of induced abortion, maternal age, and severity of maternal depression.126,181 "
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    ABSTRACT: In pregnant women with major depression, the overarching goal of treatment is to achieve or maintain maternal euthymia, thus limiting both maternal and fetal exposure to the harmful effects of untreated or incompletely treated depression. However, the absence of uniformly effective therapies with guaranteed obstetric and fetal safety makes the treatment of major depression during pregnancy among the most formidable of clinical challenges. Clinicians and patients are still faced with conflicting data and expert opinion regarding the reproductive safety of antidepressants in pregnancy, as well as large gaps in our understanding of the effectiveness of most antidepressants and nonpharmacological alternatives for treating antenatal depression. In this paper, we provide a clinically focused review of the available information on potential maternal and fetal risks of untreated maternal depression during pregnancy, the effectiveness of interventions for maternal depression during pregnancy, and potential obstetric, fetal, and neonatal risks associated with antenatal antidepressant use.
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    • "However, there are no published accounts of a meta-analysis that directly compares the teratogentic potential of common individual SSRIs that might indicate which are comparatively safer. Previous studies have reported the teratogenicity of SSRIs as a medication class (Rahimi and Abdollahi, 2006) or have examined aggregates of newer antidepressants agents (including reboxetine, venlafaxine, and bupropion ) (Einarson and Einarson, 2005). These studies might be of limited value to patients and clinicians because the teratogenic potential of specific agents might differ from the aggregate result for SSRI or non-SSRI medications as a class. "
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    ABSTRACT: Context:It has been suggested that the commonly prescribed class of antidepressants selective serotonin reuptake inhibitors (SSRIs) are associated with birth defects. However, the teratogenic effect of individual SSRIs has not been previously compared using meta-analysis.Objective:To determine the strength of the association between individual SSRIs and major, minor, and cardiac malformation among infants born to women taking these medications.Data sources:Electronic search of CINAHL, EMBASE, Medline, PsycINFO, and ISI Web of Science using the search terms (SSRI OR antidepressant) AND (obstetric outcome OR malformation OR birth outcome OR teratogen), supplemented by manual searching of published references and requests of primary researchers for unpublished data.Study selection:There were 115 studies identified by electronic search and reviewed in full text, which yielded 16 papers reporting 36 data samples for major malformations, nine papers reporting 26 data samples for cardiac malformations, and four papers reporting seven data samples for minor malformations.Data synthesis:Fluoxetine (OR 1.14, 95% CI 1.01-1.30) and paroxetine (OR 1.29, 95% CI 1.11-1.49) were associated with increased risk of major malformations. Paroxetine was associated with increased risk of cardiac malformations (OR 1.44, 95% CI 1.12-1.86). Sertraline and citalopram were not significantly associated with congenital malformation. Between-sample heterogeneity was low and a range of methodological considerations had no significant impact on effect size. There was little evidence of publication bias.Conclusions:Fluoxetine and paroxetine should be avoided in the first trimester and among those at risk of an unplanned pregnancy.
    Full-text · Article · Jun 2013 · Australian and New Zealand Journal of Psychiatry
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    • "For example, increased risk of neural defects for citalopram [8] or increased prevalence of heart defects after use of paroxetine during pregnancy [34] can be emphasized. Of course it should not be forgotten that clinical study in pregnancy and pregnant mothers has its own limitations and that is why in most of meta-analysis studies, problem of data aggregation among included studies exists [6,35-38] but they are inevitable limitations of such studies and therefore conducted meta-analyses. "
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    ABSTRACT: Selective serotonin reuptake inhibitors (SSRIs) are the most frequently used antidepressants during pregnancy. There are conflicting results about their influence on pregnancy outcomes. The goal of this study was to update our previous meta-analysis about pregnancy outcomes following exposure to SSRIs. For this purpose, all relevant databases were searched from 1990 to March 2012 for studies investigating the pregnancy outcomes following exposure to any therapeutic dosage of any SSRI (fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine) during pregnancy. Types of outcome investigated were spontaneous abortion, major malformations, cardiovascular malformations, and minor malformations. A total of 25 studies met our criteria and were included in the meta-analysis. The odds ratio (OD) values are 1.87 (95% CI: 1.5 to 2.33, P< 0.0001) for spontaneous abortion, 1.272 (95% CI: 1.098 to 1.474, P = 0.0014) for major malformations, 1.192 (95% CI: 0.39 to 3.644, P= 0.7578) for cardiovascular malformations, and 1.36 (95% CI: 0.61 to 3.04, P= 0.4498) for minor malformations. The results demonstrated that SSRIs increase the risk of spontaneous abortion and major malformations during pregnancy while they don't increase the risk of cardiovascular malformations and minor malformations. Our previous meta-analysis only showed an increase in the risk of spontaneous abortion following the use of SSRIs during pregnancy. This might be due to increase in the number of studies included or addition of two new SSRIs (citalopram and escitalopram). The message to researchers is to try considering SSRIs individually during pregnancy to reduce heterogeneity, although all are aware of inevitable limitations to study on pregnant mothers.
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