Selective Serotonin Reuptake Inhibitors Use In Pregnancy Research Articles

Selective serotonin reuptake inhibitors and preeclampsia: A quality assessment and meta-analysis.

Serotonin modulates vascular, immune, and neurophysiology and is dysregulated in preeclampsia. Despite biological plausibility that selective serotonin reuptake inhibitors (SSRIs) prevent preeclampsia pathophysiology, observational studies have indicated increased risk and providers may be hesitant. The objective of this meta-analysis and quality assessment was to evaluate the evidence linking SSRI use in pregnancy to preeclampsia/gestational hypertension. PubMed was searched through June 5, 2020 manually and using combinations of terms: "preeclampsia", "serotonin", and "SSRI". This review followed MOOSE guidelines. Inclusion criteria were: 1) Observational cohort or population study, 2) exposure defined as SSRI use during pregnancy, 3) cases defined as preeclampsia or gestational hypertension, and 4) human participants. Studies were selected that addressed the hypothesis that gestational SSRI use modulates preeclampsia and/or gestational hypertension risk. Review Manager Web was used to synthesize study findings. Articles were read and scored (Newcastle-Ottawa Quality Assessment Scale) for quality by two independent reviewers. Publication bias was assessed using a funnel plot and the Egger test. Of 179 screened studies, nine were included. The pooled risk ratio (random effects model) was 1.43 (95% CI: 1.15-1.78, P<0.001; range 0.96-4.86). Two studies were rated as moderate quality (both with total score of 6); others were high quality. Heterogeneity was high (I2=88%) and funnel asymmetry was significant (p<0.00001). Despite evidence for increased preeclampsia risk with SSRIs, shared risk factors and other variables are poorly controlled. Depression treatment should not be withheld due to perceived gestational hypertension risk. Mechanistic evidence for serotonin modulation in preeclampsia demonstrates a need for future research.

SSRI Use During Pregnancy and Risk for Postpartum Hemorrhage: A National Register-based Cohort Study in Sweden

(BJOG. 2020;127:1366–1373) Up to 1 in 6 women globally are affected by maternal mood disorders and perinatal depression, and over the course of the last 20 years, treatment with selective serotonin reuptake inhibitors (SSRIs) has dramatically increased. SSRIs remain the drug of choice for depression affecting pregnant women despite the small elevated risk of persistent pulmonary hypertension of the newborn, cardiovascular defects, and need for neonatal intensive care. However, as the use of SSRIs in nonpregnant populations is associated with elevated risk for upper gastrointestinal tract bleeding, intracranial hemorrhage, and increased postoperative blood loss, this study’s primary aim was to investigate whether or not SSRIs used by pregnant women lead to a higher risk of postpartum hemorrhage (PPH). The hypothesis was that use of SSRIs in pregnancy would increase the risk of PPH in women with low-risk pregnancies in Sweden.

Selective Serotonin Reuptake Inhibitors during Pregnancy: Do We Have Now More Definite Answers Related to Prenatal Exposure?

Despite extensive studies, there still seems to be uncertainty as to the possible reproductive risk of selective serotonin reuptake inhibitors (SSRIs) and selective serotonin norepinephrine reuptake inhibitors (SNRIs) in pregnancy. We, therefore, assess the current data on the risk/benefit of SSRI use in pregnancy. As the neurodevelopmental effects of SSRIs are discussed in another paper in this issue, we will not address the possible neurodevelopmental effects. Special emphasis is given to the newer, large population-based studies. Most studies have shown that the overall risk of major malformations is similar to that in unexposed children, except for some small increased risk for cardiac anomalies. Persistent pulmonary hypertension of the newborn has also been described with a low absolute risk of <1%, less than twice that observed in nonexposed newborns. Poor neonatal adaptation was described in up to 25% of exposed neonates. However, newer population-based studies have also shown similarly high rates among offspring of women with untreated depression. There is a higher risk for psychiatric problems possibly related to the maternal psychiatric disease for which SSRIs were prescribed. Judging from the new population registry-based studies with comparison to disease controls, there seems to be no demonstrable increase in the rate of major anomalies, prematurity, small for gestational age, or miscarriage. Therefore, the risk associated with treatment discontinuation (e.g., higher frequency of relapse, and postpartum depression) appears to outweigh the fetal and neonatal risks of maternal treatment. Thus, following appropriate explanation regarding possible risks, treatment should continue during pregnancy with minimal effective doses. Birth Defects Research 109:898-908, 2017. © 2017 Wiley Periodicals, Inc.

Are SSRIs during pregnancy safe? More studies seek answers

Are SSRIs during pregnancy safe? More studies seek answers

Fluoxetine effect on gestation and fetal development

Abstract 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. Compared to the controlled group, in which weight gain was more significant, the animals from the experimental group had a slight increase in body weight. The weight gain normally induced by gestation, is less significant in fluoxetine treated rats due to the increase serotonin levels in the brain. The uteri examination of pregnant rats showed an increase in the number of dead and resorbed rat embryos. Preclinical studies suggest that the inclusion of fluoxetine in pregnancy category C is justified and the appropriateness of its administration in pregnancy is still an unresolved issue.

Selective serotonin reuptake inhibitors and pregnancy: A review of maternal, fetal and neonatal risks and benefits.

Depression is common in women of childbearing age. Whereas non-pharmacological interventions are recommended as first line interventions, pharmacological treatment may be required. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressants in pregnancy. Ideally, discussion of the risks and benefits of SSRI use in pregnancy should occur prior to pregnancy. The potential risks of psychotropic medications need to be balanced against the risks associated with untreated psychiatric conditions and the discontinuation of necessary medications.

Use of selective serotonin reuptake inhibitors and lifestyle among women of childbearing age: a Danish cross-sectional survey

ObjectiveTo examine the use of selective serotonin reuptake inhibitors (SSRIs) among Danish women of childbearing age according to lifestyle factors.DesignCross-sectional survey.SettingThe Central Denmark Region.Participants4234 women (71.5% of the invited women)...

Drug exposure: inclusion of dispensed drugs before pregnancy may lead to underestimation of risk associations

ObjectivesTo assess the impact of exposure misclassification on risk associations when using prescription databases as the source for drug exposure in pregnancy by applying results from a validation analysis of exposure classification. Study Design and SettingLinkage of data on 27,656 participants in the Norwegian Mother and Child Cohort Study (MoBa) with the Norwegian Prescription Database (NorPD). Exposure to selective serotonin reuptake inhibitors (SSRIs) was defined by dispensed drugs during pregnancy including different time windows before pregnancy. The validity of NorPD data was estimated using self-reported use in MoBa as the reference standard. We applied the results from the validation analysis on data from a Nordic study on SSRI use in pregnancy and risk of persistent pulmonary hypertension in the newborn. ResultsSensitivity increased and specificity decreased when the time window in NorPD was expanded before pregnancy. Using the same time window as in the Nordic study (+90 days before pregnancy), for use in early pregnancy, the odds ratio (OR) corrected for misclassification was 2.6 compared with the OR of 1.6 in the Nordic study. ConclusionExpansion of the time window to include intervals before pregnancy can lead to lower specificity and underestimation of risk associations.

Use of SSRIs in Pregnancy: Neonatal Implications

ing pregnancy, and (4) implications of drug transfer to the infant via breast milk. Using a case study approach and a systematic appraisal of the risks-benefits-alternative model, this article will consider the scientific evidence surrounding fetal and neonatal exposure to SSRIs in the perinatal period and via breast milk, Depressed mood in pregnancy and the postpartum period is commonly acknowledged as a risk factor for both mother and baby. Selective serotonin reuptake inhibitors (SSRIs) have increasingly been used to treat perinatal mood disorders; however, new risks related to the use of specific SSRI agents have been documented. Research into adverse effects of SSRI use in pregnancy has focused primarily on four areas: (1) congenital defects stemming from first trimester exposure, (2) neonatal behavioral effects secondary to third trimester exposure, (3) maternal and fetal outcomes resulting from suspending antidepressant therapy durDepressed mood

Increase in use of selective serotonin reuptake inhibitors in pregnancy during the last decade, a population‐based cohort study from the Netherlands

* Recently, the use of selective serotonin reuptake inhibitors (SSRIs), particularly paroxetine, in pregnancy has been associated with an increased risk on specific birth defects or other adverse pregnancy outcomes. * However, the extent of SSRI use in pregnancy is largely unknown. * In the last decade the use of SSRIs in the year preceding delivery has increased twofold. * This increase runs parallel with the increase in use of SSRIs among women of fertile age. * Paroxetine is one of the most commonly used SSRIs. * Only recently have sufficient data become available on the use of paroxetine to detect moderate increased risks for specific malformations. * The safety of SSRIs which are less frequently used is not yet established. * Case-control birth defect-monitoring systems may be helpful in providing safety and risk estimates that become more precise as data accumulate for these drugs. Recent case-control studies suggest a relationship between the use of selective serotonin reuptake inhibitors (SSRIs) and the occurrence of birth defects and other adverse pregnancy outcomes. The aim was to determine the extent of the use of SSRIs before and during pregnancy and its trend over the years 1995-2004 in the Netherlands. The study was performed with data from a population-based prescription database. Within this database, women giving birth to a child between 1995 and 2004 were identified. The exposure rate and 95% confidence interval (CI) were calculated as the number of pregnancies per 1000 that were exposed to an SSRI in a defined period (per trimester or in the year preceding delivery). Exposure rates were calculated for 2-year periods: 1995/1996, 1997/1998, 1999/2000, 2001/2002 and 2003/2004. Trends in exposure rates were analysed using the chi(2) test for trend. Included were 14,902 pregnancies for which complete pharmacy records were available from 3 months before pregnancy until delivery. A total of 310 pregnancies were exposed to an SSRI in the year preceding delivery. The exposure rate increased from 12.2 (95% CI 7.0, 19.8) in 1995/1996 to 28.5 (95% CI 23.0, 34.9) in 2003/2004. There has been a significant increase in the use of SSRIs among pregnant women in the Netherlands over the last 10 years, parallel with the increase in exposure in women of fertile age. In light of the recent warnings about the use of SSRIs in pregnancy, healthcare professionals should be careful in prescribing SSRIs to women planning a pregnancy.

Metareview on Short-Term Effectiveness and Safety of Antidepressants for Depression: An Evidence-Based Approach to Inform Clinical Practice

To examine the available scientific literature for answers to clinically relevant questions regarding the effectiveness and tolerability of antidepressant drugs (ADs) for the acute phase treatment of depression and to assess the degree to which the literature supports the findings. We used several sources to identify primary reviews: MEDLINE (1955 to April 2006), EMBASE (1980 to April 2006), PsycINFO (1980 to April 2006), and the Cochrane Library 2006 Issue 1. Additional searches were also carried out on the following databases of the National Health Service Centre for Reviews and Dissemination: Abstracts of Reviews of Effects, Health Technology Assessment, and Turning Research into Practice. We also searched the National Institute of Health and Clinical Excellence guidance website. We carried out a metareview of selected high-quality systematic reviews of short-term pharmacologic interventions with ADs for major depression. To assess efficacy, we followed the hierarchy of evidence proposed by the Centre for Evidence Based Medicine (Oxford), including only reviews of randomized controlled trials. To assess tolerability, we also considered observational data when randomized evidence was not available. There was randomized evidence that ADs are efficacious in primary care settings and that there may be small, but clinically important, differences in efficacy between ADs. There was no good evidence that an AD combined with an antipsychotic is superior to AD monotherapy in cases of psychotic depression or that intravenous administration leads to more rapid response. There was evidence that monoamine oxidase inhibitors are superior to tricyclic antidepressants, but not to selective serotonin reuptake inhibitors (SSRIs), in treating atypical depression. There is some evidence of harm related to the use of SSRIs in pregnancy but not to their use when breastfeeding. There is evidence that SSRIs may increase suicidal thoughts, but not actual suicide, in early-phase therapy. We found a substantial body of evidence regarding the benefits and harms of ADs in the treatment of depressive disorder. Nonetheless, there remains considerable residual uncertainty. The evidence is inadequate for generally applicable recommendations; in most cases, the balance between risks and benefits will need to be considered for individual patients. Clinicians should also be guided by the recommendations and warnings issued by drug regulatory authorities.

Use of Selective Serotonin-Reuptake Inhibitors in Pregnancy and the Risk of Birth Defects

Information regarding the safety of selective serotonin-reuptake inhibitors (SSRIs) in human pregnancy is sparse. Concern has been raised about the risk of congenital heart defects associated with the use of SSRIs in pregnancy. We obtained data on 9622 case infants with major birth defects and 4092 control infants born from 1997 through 2002 from the National Birth Defects Prevention Study. Case infants were ascertained through birth-defects surveillance systems in eight U.S. states; controls were selected randomly from the same geographic areas. Mothers completed a standardized telephone interview regarding exposure to potential risk factors, including medications, before and during pregnancy. Exposure to SSRIs was defined as treatment with any SSRI from 1 month before to 3 months after conception. Birth defects were assigned to 26 categories and subcategories. There were no significant associations between maternal use of SSRIs overall during early pregnancy and congenital heart defects or most other categories or subcategories of birth defects. Maternal SSRI use was associated with anencephaly (214 infants, 9 exposed; adjusted odds ratio, 2.4; 95% confidence interval [CI], 1.1 to 5.1), craniosynostosis (432 infants, 24 exposed; adjusted odds ratio, 2.5; 95% CI, 1.5 to 4.0), and omphalocele (181 infants, 11 exposed; adjusted odds ratio, 2.8; 95% CI, 1.3 to 5.7). Maternal use of SSRIs during early pregnancy was not associated with significantly increased risks of congenital heart defects or of most other categories of birth defects. Associations were observed between SSRI use and three types of birth defects, but the absolute risks were small, and these observations require confirmation by other studies.

To treat or not to treat: maternal depression, SSRI use in pregnancy and adverse neonatal effects

Recent pharmaceutical company and regulatory body circulars warning against the use of selective serotonin reuptake inhibitors (SSRIs) in late pregnancy have left clinicians in somewhat of a quandary as to how to manage their more severely depressed patients in pregnancy. Conversely, up to 75% of depressed women ceasing their antidepressants periconceptually will relapse. Studies reporting on adverse neonatal outcomes following exposure to SSRIs in the latter half of pregnancy suggest that the fetus is exposed to significant concentrations of these medications during this time. Adverse neonatal effects affecting the respiratory, gastrointestinal and neurological systems are, however, predominantly mild and self-limiting. One small retrospective case study suggests that SSRI exposure in the latter half of pregnancy may be associated with an increased risk of persistent pulmonary hypertension of the neonate (PPHN), however, the absolute risk of developing PPHN remains very small and these findings will require replication with a prospective study. While the studies to date suggest the need to closely monitor SSRI-exposed neonates in the immediate postnatal period, preferably with a neonatal withdrawal scale and access to neonatology services, there is currently no clear argument for women to be weaned off their SSRI in late pregnancy. The decision to use SSRIs at this time will have to be made on a case-by-case basis in close consultation with the mother and her partner.

Neonatal Withdrawal After SSRI Use in Pregnancy

Withdrawal symptoms from selective serotonin reuptake inhibitors (SSRIs) are well known. Withdrawal symptoms in newborns -- notably, convulsions,

Selective serotonin reuptake inhibitors in pregnancy and lactation.

Selective serotonin reuptake inhibitors (SSRIs) have become the agents of first choice in the treatment of depression because of their safe side effect profile. This paper reviews the current literature on the use of SSRIs in pregnancy and lactation concerning their safety. There are human studies that only used fluoxetine in pregnancy, which established its safety. SSRIs are excreted in breast milk, and their long-term effects on the newborn are unknown at this time. The decision to use SSRIs in pregnancy should be made on a case by case basis with active involvement of the patient in the informed consent process during which the risks and benefits are discussed and documented.

Selective serotonin-reuptake inhibitors in pregnancy and lactation.

We explore the effects on the developing fetus and neonate of selective serotonin-reuptake inhibitors (SSRIs) during pregnancy and lactation, reviewing the relevant animal and human studies published in English from 1976 to the present. Medline was used to search the terms SSRI, fluoxetine, pregnancy, lactation, and teratogenesis. Animal studies were inconclusive: some found that fetal exposure to high doses of fluoxetine produced no congenital anomalies, while others linked the drug to abnormalities such as craniofacial malformations, alterations in serotonergic neurotransmitter systems, birth-related hematomas, and inhibition of the milk-ejection reflex. Human investigations indicated no relationship between in utero exposure to fluoxetine and teratogenic effects, although data are limited, and none have been collected regarding behavioral teratogenesis. However, we found a suggestion of an increased rate of miscarriage, an association with infants large for gestational age, one reported case of perinatal toxicity, and one case of an infant who was colicky while receiving breast milk from a mother taking fluoxetine. Based on these data, controlled prospective studies of exposure to SSRIs during pregnancy and lactation are needed, as is long-term evaluation for behavioral teratogenesis and enduring cognitive effects. Data are lacking on drug levels in breast milk and neonatal serum. Neonatal toxicity and the effect of SSRIs on labor and delivery, the mother-infant interaction, and lactation also merit further study. Clinically, a conservative approach is encouraged, minimizing the use of SSRIs in pregnancy, avoiding such drugs during the first trimester, tapering them prior to delivery, and discouraging breast-feeding during their use.