Article

Bar-Oz B, Einarson T, Einarson A, et al.. Paroxetine and congenital malformations: meta-analysis and consideration of potential confounding factors

Motherisk Program, The Hospital for Sick Children, Toronto, Ontario, Canada.
Clinical Therapeutics (Impact Factor: 2.59). 06/2007; 29(5):918-26. DOI: 10.1016/j.clinthera.2007.05.003
Source: PubMed

ABSTRACT Antidepressants have been commonly used by women of childbearing age. Recent studies suggest that paroxetine, a selective serotonin reuptake inhibitor (SSRI), might specifically increase teratogenic risk.
The purpose of this study was to quantify first-trimester exposure to paroxetine and birth defects and examine potential sources of bias in the in utero or postnatal detection of more congenital malformations among women with depression. We also sought to examine whether paroxetine was used for the same indications as other SSRIs among pregnant women.
This meta-analysis was designed to quantify malformation rates associated with the use of paroxetine. A search of the literature from 1985 to 2006 (English language) found in MEDLINE, EMBASE, REPROTOX, Scopus, and Biological Abstracts was conducted using the following terms: pregnancy outcome, congenital or fetal AND anomalies, malformations, cardiac/heart defects, AND selective serotonin reuptake inhibitors, paroxetine, and Paxil. Administrative databases of medication and medical services use in the Province of Quebec, Canada, were used to calculate the rates of ultrasound and echocardiogram in pregnancy and infancy in women/infants exposed to SSRIs and to compare the indications for general SSRI use versus paroxetine use.
Based on the studies analyzed, first-trimester paroxetine exposure was associated with a significant increase in the risk for cardiac malformation (odds ratio [OR], 1.72; 95% CI, 1.22-2.42). Women using antidepressants in pregnancy had a 30% higher rate of utilization of ultrasound in pregnancy. Infants of women who received SSRIs underwent approximately twice as many echocardiograms in the first year of life compared with children of women who used nothing. Significantly more women receiving paroxetine used the drug for anxiety or panic than women receiving other SSRIs (OR, 4.11; 95% CI, 2.39-7.08).
Based on the results of this metaanalysis, first-trimester exposure to paroxetine appears to be associated with a significant increase in the risk for cardiac malformation. However, a detection bias cannot be ruled out as contributing to the apparent increased detection of cardiovascular malformation of children exposed in utero to paroxetine. A significantly greater number of women were using paroxetine for anxiety or panic when compared with women using other SSRIs.

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    • "However , certain standard mood stabilizers (e.g., divalproex sodium) have teratogenic effects in the first trimester (Cohen 2007). Likewise, questions have been raised about the safety of selective serotonin reuptake inhibitors in women with MDD (Bar-Oz et al. 2007). Thus, preventative psychosocial treatments are as relevant in the preconception phase as in pregnancy or the postpartum phases, especially among women with mood disorders who seek alternatives to pharmacotherapy. "
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    ABSTRACT: The perinatal period is a high-risk time for mood deterioration among women vulnerable to depression. This study examined feasibility, acceptability, and improvement associated with mindfulness-based cognitive therapy (MBCT) in perinatal women with major depressive disorder (MDD) or bipolar spectrum disorder (BSD). Following a diagnostic evaluation, 39 perinatal women with a lifetime history of MDD (n = 27) or BSD (n = 12) enrolled in an 8-week program of MBCT classes (2 h each) that incorporated meditation, yoga, and mood regulation strategies. Participants were pregnant (n = 12), planning pregnancy (n = 11), or up to 1-year postpartum (n = 16). Participants were self-referred and most had subthreshold mood symptoms. Assessments of depression, (hypo)mania, and anxiety were obtained by interview and self-report at baseline, post-treatment and at 1- and 6-month post-treatment. Women with a history of MDD were more likely to complete the classes than women with BSD. Of 32 women who completed the classes, 7 (21.9 %) had a major depressive episode during the 6-month post-treatment follow-up. On average, participants with MDD reported improvements in depression from pre- to post-treatment. Mood improvement was not observed in the BSD group. In the full sample, improvements in depression symptoms across time points were associated with increasing mindful tendency scores. This study was limited by its uncontrolled design, heterogeneous sample, and questionnaire-based assessment of mindfulness skills. MBCT may be an important component of care for perinatal women with histories of major depression. Its applicability to perinatal women with BSD is unclear.
    Cognitive Therapy and Research 01/2015; DOI:10.1007/s10608-015-9681-9 · 1.70 Impact Factor
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    • "The majority of individual studies have not demonstrated increased risk of MCMs associated with antidepressant exposure in the first trimester or at any time during pregnancy.87,89,92–104 Meta-analyses of studies investigating the risk of antidepressants and “any” or “overall” MCMs have shown either small but statistically significant risk105,106 or absence of significant increase in risk (Table 2).107–110 "
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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.
    Drug, Healthcare and Patient Safety 09/2014; 6:109-29. DOI:10.2147/DHPS.S43308
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    • "However, this rating was based on nonpeer-reviewed and unpublished data released by the manufacturer. Peer-reviewed analysis of this database revised the incidence of cardiac malformation in the study population downwards (Queisser-Luft et al., 2002), and subsequent meta-analyses of the possible teratogenic effects of paroxetine have yielded conflicting results (Bar-Oz et al., 2007; O'Brien et al., 2008; Wurst et al., 2010). Doubts about the safety of paroxetine have led to recommendations that its use be avoided in early pregnancy in favour of other antidepressants (Udechuku et al., 2011). "
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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.
    Australian and New Zealand Journal of Psychiatry 06/2013; 47(11). DOI:10.1177/0004867413492219 · 3.77 Impact Factor
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