Effect of Low and High Doses of Two Selective Serotonin Reuptake Inhibitors on Pregnancy Outcomes and Neonatal Mortality (original) (raw)
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Selective serotonin reuptake inhibitors in human pregnancy: On the way to resolving the controversy
Seminars in Fetal and Neonatal Medicine, 2013
Major anomalies Neonatal effects Persistent pulmonary hypertension Neurodevelopmental effects Selective serotonin reuptake inhibitors (SSRIs) s u m m a r y There has been an increase in the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy. However, in the last 10 years, in spite of a vast literature regarding use in pregnancy there seems to be some confusion as to the possible risk of these drugs, especially related to cardiovascular anomalies. In addition, there are data on developmental follow-up studies that raise the question of possible slight developmental and neurobehavioral problems. The purpose of the present review is therefore to critically summarize the current evidence for the risk/benefit analysis of SSRI use in human pregnancy. Although most studies have not shown an increase in the overall risk of major malformations, several have suggested that the use of SSRIs may be associated with a small increased risk for cardiovascular malformations. However, new compelling evidence shows that this apparent increased risk occurs also in women with untreated depression, highlighting the probable ascertainment bias involved in many of these studies. Persistent pulmonary hypertension of the newborn (PPHN) has also been described with an absolute risk of <1%; however, here too, higher rates were described among offspring of women with untreated depression. Poor neonatal adaptation has been described in up to 30% of neonates exposed to SSRIs late in pregnancy. Of the few postnatal developmental follow-up studies, there are no significant developmental problems. The literature on SSRIs in pregnancy is somewhat confusing but when analysing all prospective cohort data there seems to be no demonstrable increase in the rate of major anomalies or developmental disorders. When evaluating the risk/benefit ratio of SSRI treatment in pregnancy, the risk associated with treatment discontinuation e e.g. higher frequency of relapse, increased risk of preterm delivery and postpartum depression e appear to outweigh the potential, unproven risks of treatment. Moreover, maternal depression may negatively affect the child's development, emphasizing the importance of prevention by appropriate treatment during pregnancy with the least minimal effective dose.
Journal of Affective Disorders, 2011
Objective: The purpose of this study was to evaluate the effects of prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) on obstetrical and neonatal outcomes. Method: A case-control study was conducted to compare perinatal outcomes among pregnant women with affective disorder (DSM-IV criteria) and who received SSRIs during pregnancy with those of women without an active psychiatric disorder during pregnancy who were nonexposed to antidepressants during pregnancy. Each case was matched to two controls for maternal age (± 2 years) and parity. Results: A total of 252 women were enrolled in the study, 84 exposed and 168 non-exposed. Demographic and clinical characteristics did not differ significantly between the groups. The rates of prelabor rupture of membranes, induction of labor and cesarean delivery were slightly higher but not statistically significant in the exposed group. The mean gestational age at birth was 38.8 (± 1.86) weeks for the exposed group and 39.4 (±1.52) weeks for the non-exposed group (p = .005). Rates for preterm birth were higher in the exposed group (OR = 3.44, 95% CI = 1.30-9.11). After stratification for dose, it was found that exposure to a high-dose was associated with lower gestational age (p = .009) and higher rates of prematurity (OR = 5.07, 95% CI = 1.34-19.23). The differences remained significant after controlling for maternal status and the length of exposure. Conclusion: Women treated with SSRIs during pregnancy, mainly at high-dose, had an increased risk of preterm birth compared to healthy women of similar age and parity who were not exposed to SSRI during pregnancy.
Fluoxetine effect on gestation and fetal development
Acta Medica Marisiensis, 2014
The prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) is very controversial. There is no conclusive evidence for increased risk of malformations after SSRI use in pregnancy. The aim of the study was to determine how fluoxetine is affecting gestation and fetal development in rats. Twenty sexually mature female Wistar rats weighting between 250-260 g received 20 mg/kg body weight fluoxetine from the first day of gestation and during the entire gestation period.The drug was administered by oral route. Healthy, primipareus animals were selected along with 20 female Wistar rats, as control group. Mature males were caged with virgin females for an entire week. Rat’s behaviour during gestation, after birth and rats body weight was examined. The number of healthy pups was also noted. The females not giving birth after 21 days to any pup were anesthetized (halothane through gas scavenging apparatus untilled death) and the gravid uterus were dissected out and examined. Comp...
Archives of General Psychiatry, 2012
Selective serotonin reuptake inhibitors (SSRIs) are frequently prescribed to pregnant women, but knowledge about their unintended effects on child health is scarce. Objective: To examine the effects of maternal SSRI use during pregnancy on fetal growth and birth outcomes. Design: The study was embedded in the Generation R Study, a prospective population-based study from fetal life onward. Participants: Seven thousand six hundred ninety-six pregnant women were included. Selective serotonin reuptake inhibitor use was assessed by questionnaires in each trimester and verified by pharmacy records. Using depressive symptom scores from the Brief Symptom Inventory, 7027 pregnant mothers (91.3%) had no or low depressive symptoms, 570 pregnant mothers (7.4%) had clinically relevant depressive symptoms and used no SSRIs, and 99 pregnant mothers (1.3%) used SSRIs. Main Outcome Measures: Fetal ultrasonography was performed in each trimester. We determined fetal body and head growth with repeated assessments of body and head size. The birth outcomes studied were preterm birth, small for gestational age, and low birth weight. Results: Fetuses from mothers with prenatal depressive symptoms showed reduced body growth (=−4.4 g/wk; 95% CI: −6.3 to −2.4; PϽ.001) and head growth (=−0.08 mm/wk; 95% CI: −0.14 to −0.03; P=.003). Mothers using SSRIs during pregnancy had fewer depressive symptoms than mothers in the clinical symptom range. Prenatal SSRI use was not associated with reduced body growth but was associated with reduced fetal head growth (=−0.18 mm/ wk; 95% CI: −0.32 to −0.07; P=.003). The SSRI-exposed children were at higher risk for preterm birth (odds ra-tio=2.14; 95% CI: 1.08 to 4.25; P=.03). Conclusions: Untreated maternal depression was associated with slower rates of fetal body and head growth. Pregnant mothers treated with SSRIs had fewer depressive symptoms and their fetuses had no delay in body growth but had delayed head growth and were at increased risk for preterm birth. Further research on the implications of these findings is needed.
Basic & Clinical Pharmacology & Toxicology, 2013
The present study evaluated the reproductive effects of fluoxetine exposure in utero and during lactation on pregnancy outcomes and the sexual development of offspring. Pregnant Wistar rats were treated daily with fluoxetine (0.4, 1.7 and 17 mg/kg/day) or distilled water by gavage from gestation day (GD) 7 to lactation day (LD) 21. A significant reduction in maternal body weight was observed during pregnancy and lactation in dams exposed to 17 mg/kg fluoxetine. Hormone analysis revealed an increase in progestagen and glucocorticoid metabolites on GD 15 and estrogen and progestagen metabolites on LD 7 in dams treated with 17 mg/kg fluoxetine. Estrogen metabolites also were increased on LD 7 in dams treated with 0.4 mg/kg fluoxetine. Besides that, an increase in the weight of the adrenal glands and a reduction in uterine weight in dams exposed to highest dose of fluoxetine was observed. Finally, pup birth weight and the viability and weaning indices also were reduced in animals exposed to 17 mg/kg fluoxetine. Overall, maternal hormonal changes were only observed at the highest dose tested, which also induced maternal and foetal toxicity. No significant changes were seen in dams or offspring exposed to therapeutic-like doses.
Safety of Selective Serotonin Reuptake Inhibitors in Pregnancy
Cns Drugs, 2009
Psychiatric treatment with selective serotonin reuptake inhibitors (SSRIs) may be desirable or necessary during pregnancy; however, the benefit of these treatments must balance the benefits to the mother with any risk to the developing foetus. At the present time, the role of serotonin in normal central nervous system development, as well as the effects of altering serotonin transmission at critical periods of embryo development, remains to be further clarified. Depression has a high prevalence in pregnant women (around 10%) and approximately one-half of the pregnancies are unplanned, making necessary that physicians have to know the risks associated with the decision to use this kind of antidepressants during pregnancy. The effects of antidepressants in pregnancy could be classified in several main categories: the teratogenic possible effects; the effects on the normal development of the brain and neuropsychological functions; the effects on birth weight and/or early delivery; the risk of increased bleeding on the mother during delivery; the neuropsychological behaviour and adaptation after delivery, including not only neonatal withdrawal syndromes but also pain reactivity and increased parasympathetic cardiac modulation during recovery after an acute noxious event and in a wide range of neurobehavioural outcomes; and medium-to long-term effects in neurocognitive functions in those children. These areas are reviewed according to the most recent published cohort-controlled studies and prospective surveys regarding SSRIs use in pregnancy. The review tries to clarify the blurred aspects of the use of SSRI during pregnancy and to give sensible and up-to-dated guidelines for the treatment of psychiatric disorders with SSRI during pregnancy.
Selective Serotonin Reuptake Inhibitors in Human Pregnancy: To Treat or Not to Treat?
Obstetrics and Gynecology International, 2012
Selective serotonin reuptake inhibitors (SSRIs) are increasingly prescribed during pregnancy. The purpose of the present paper is to summarize and evaluate the current evidence for the risk/benefit analysis of SSRI use in human pregnancy. The literature has been inconsistent. Although most studies have not shown an increase in the overall risk of major malformations, several studies have suggested that SSRIs may be associated with a small increased risk for cardiovascular malformations. Others have noted associations between SSRIs and specific types of rare major malformations. In some studies, there appears to be a small increased risk for miscarriages, which may be associated with the underlying maternal condition. Neonatal effects have been described in up to 30% of neonates exposed to SSRIs late in pregnancy. Persistent pulmonary hypertension of the newborn has also been described with an absolute risk of < 1%. The risk associated with treatment discontinuation, for example, higher frequency of relapse and increased risk of preterm delivery, should also be considered. The overall benefit of treatment seems to outweigh the potential risks.
Fluoxetine-induced perinatal morbidity in a sheep model
Frontiers in Medicine
Selective serotonin reuptake inhibitors (SSRI) are the most common antidepressants used by pregnant women. However, adverse pregnancy outcomes have been described in women taking SSRI during pregnancy—placental lesions, premature birth, poor neonatal adaptation. We aimed to investigate the effects of fluoxetine (Prozac® most commonly used SSRI) treatment during the last month of gestation on pregnancy complications, placental and neonatal health in a non-depressed sheep model. On day 119 ± 1 postbreeding (experimental day 0; E0) of a 151-day expected gestation, Hampshire ewes were randomly assigned to receive fluoxetine (n = 9 ewes, 15 lambs; daily intravenously treatment with 10 mg/kg on E0 and E1 and 5 mg/kg daily thereafter until parturition) or to a control group (n = 10; 14 lambs; vehicle only). Blood samples from ewes were collected throughout the experimental period and postpartum; blood from lambs were collected postpartum. Analysis of variance was used for statistical analy...