SSRIs and the developing brain

Child Study Center, Yale University School of Medicine, New Haven, CT 06520, USA.
The Lancet (Impact Factor: 45.22). 02/2005; 365(9458):451-3. DOI: 10.1016/S0140-6736(05)17877-5
Source: PubMed
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    • "Paroxetine was associated with neonatal convulsions and cases of neonatal withdrawal were reported after exposure to all SSRI drugs. Based upon these data, Ruchkin and Martin recommended that the threshold for prescribing these compounds during pregnancy and in the postpartum should be raised[22]. Concerns about these compounds have also led to an interest in complementary and alternative methods of preventing or treating MDD. "
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    ABSTRACT: Major depressive disorder (MDD) during pregnancy and postpartum depression are associated with significant maternal and neonatal morbidity. While antidepressants are readily used in pregnancy, studies have raised concerns regarding neurobehavioral outcomes in exposed infants. Omega-3 fatty acid supplementation, most frequently from fish oil, has emerged as a possible treatment or prevention strategy for MDD in non-pregnant individuals, and may have beneficial effects in pregnant women. Although published observational studies in the psychiatric literature suggest that maternal docosahexaenoic acid (DHA) deficiency may lead to the development of MDD in pregnancy and postpartum, there are more intervention trials suggesting clinical benefit for supplementation with eicosapentaenoic acid (EPA) in MDD. The Mothers, Omega-3 and Mental Health study is a double blind, placebo-controlled, randomized controlled trial to assess whether omega-3 fatty acid supplementation may prevent antenatal and postpartum depressive symptoms among pregnant women at risk for depression. We plan to recruit 126 pregnant women at less than 20 weeks gestation from prenatal clinics at two health systems in Ann Arbor, Michigan and the surrounding communities. We will follow them prospectively over the course of their pregnancies and up to 6 weeks postpartum. Enrolled participants will be randomized to one of three groups: a) EPA-rich fish oil supplement (1060 mg EPA plus 274 mg DHA) b) DHA-rich fish oil supplement (900 mg DHA plus 180 mg EPA; or c) a placebo. The primary outcome for this study is the Beck Depression Inventory (BDI) score at 6 weeks postpartum. We will need to randomize 126 women to have 80% power to detect a 50% reduction in participants' mean BDI scores with EPA or DHA supplementation compared with placebo. We will also gather information on secondary outcome measures which will include: omega-3 fatty acid concentrations in maternal plasma and cord blood, pro-inflammatory cytokine levels (IL-1β, IL-6, and TNF-α) in maternal and cord blood, need for and dosage of antidepressant medications, and obstetrical outcomes. Analyses will be by intent to treat. This study compares the relative effectiveness of DHA and EPA at preventing depressive symptoms among pregnant women at risk. Clinical trial registration number: NCT00711971.
    Full-text · Article · Jun 2011 · BMC Pregnancy and Childbirth
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    ABSTRACT: Pharmacotherapy in pregnant women is often necessary to treat chronic or relapsing depression or anxiety disorders. Studies that have evaluated the safety of selective serotonin reuptake inhibitors (SSRIs) in early pregnancy have not shown an enhanced risk of major congenital malformations and these results may have contributed to the increasing use of these agents during pregnancy. Fewer studies have assessed the safety of SSRIs in the third trimester of pregnancy. This article reviews available human data on the safety of SSRI treatment in the third trimester. The main purpose is to present and discuss the existing literature on the risks to the infant and to suggest treatment guidelines for the use of SSRIs in late pregnancy. The use of SSRIs in the third trimester has shown various perinatal complications, most frequently respiratory distress, irritability and feeding problems. Further studies are needed to evaluate the frequency of these complications and to elucidate whether the symptoms represent a direct serotonergic effect or are a drug withdrawal effect. Studies have shown conflicting results with respect to whether SSRI exposure decreases birthweight and increases the risk of premature delivery. A few case reports have described intracerebral haemorrhage in neonates after maternal SSRI treatment, but it is not known whether the frequency of such complications is higher than in unexposed neonates. Data on possible long-term effects of prenatal SSRI exposure on psychomotor and behavioural development are very sparse. Our interpretation of the current literature suggests that the risk of not receiving adequate antidepressant treatment in the third trimester when indicated outweighs the risks of adverse events in the infant. Thus, adequate pharmacological treatment should not be withheld from a depressed pregnant woman in late pregnancy. However, the neonate should be monitored for possible adverse effects after maternal use of an SSRI in the third trimester.
    No preview · Article · Feb 2005 · Drug Safety
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    ABSTRACT: The aim of this review was to assess existing information about the long-term neurocognitive development of children whose mothers took SSRIs during pregnancy and/or breastfeeding. The available literature consists of 11 studies (examining a total of 306 children) that demonstrate no impairment of infant neurodevelopment following prenatal and/or postnatal exposure to SSRIs, and two studies (examining 81 children) that suggest possible unwanted effects of fetal SSRI exposure. These unwanted effects included subtle effects on motor development and motor control. Thus, the available data are not unanimous in excluding possible long-term detrimental neurodevelopmental sequelae of intrauterine exposure to SSRIs. However, it is clear that the research suggesting a lack of adverse events on infants' neurocognitive development is much more numerous and methodologically better conducted than the studies showing possible unwanted effects. Nevertheless, all reviewed studies had procedural inadequacies, and the screening instruments used have limitations, especially in the evaluation of infants. Furthermore, it is not advisable to extend the generalisations emerging from the findings of a few trials to every infant. Some infants may experience difficulties in metabolising the drugs and/or their metabolites, so the benign outcome described for most infants may not occur. Thus, the findings emerging from the reports are inconclusive and are not able to fully clarify the repercussions of maternal SSRI treatment on infants' long-term neurocognitive development. Further large, simple and well designed, randomised, prospective studies will be required for this purpose. These should also be of adequate length and performed using reproducible neurophysiological parameters in order to firmly establish the safety of these medications.
    Full-text · Article · Feb 2005 · CNS Drugs
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