Selective Serotonin Reuptake Inhibitors In Pregnancy Research Articles

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.

Dispensing patterns of selective serotonin reuptake inhibitors before, during and after pregnancy: a 16-year population-based cohort study from the Netherlands

Management of mental illness in the perinatal period with antidepressants is controversial, since evidence emerged on potential harmful effects to the unborn child. However, over time, the dispensing of antidepressants in the perinatal period has increased. We examined perinatal dispensing patterns over time and the role of a recently issued guideline in this regard. We identified a 16-year cohort of 153,952 Dutch pregnancies with a delivery date between January 1999 and December 2014. Data included exposure to selective serotonin reuptake inhibitors (SSRIs) related to phases of pregnancy (preconception, pregnancy and delivery, post-delivery). The chi-square test for trends was used. With standard logistic regression, we explored the influence of patient characteristics on continuation of SSRIs during pregnancy. A persistent significant rise of dispensing rates in all phases was observed, with the largest increase during pregnancy (from 0.8% in 1999/2000 to 2.1% in 2013/2014, chi-square for trend = 141.735, p < 0.001). A substantial change of practice in terms of the SSRI used (less paroxetine) and the policy towards continuation into pregnancy (more continuation over time) was visible. Concomitant use of psycholeptics halved the probability of continuation of SSRIs (OR 0.50, 95%CI 0.43–0.55, p < 0.01). Dispensing rates of SSRIs steadily increased last 16 years, especially during pregnancy, caused by an increase in the proportion of women continuing their medication during pregnancy. In view of the demonstrated impact of uncertainty regarding effectiveness and safety of SSRIs in pregnancy, future research should involve more detailed outcome research of SSRIs as it is, and research into viable alternatives.

Selective Serotonin Reuptake Inhibitor Use in Pregnancy: Repercussions on the Oblivious Passenger

Depression is one of the most common comorbidities in pregnancy, and use of selective serotonin reuptake inhibitors (SSRIs) has become increasingly more common during this period. For this reason it is essential to understand the implications of SSRI use on fetal development and neonatal complications. As reviewed here, the preponderance of evidence suggests that the risk of teratogenicity with SSRI use is low. Poor neonatal adaptation or withdrawal syndrome is common among neonates exposed to SSRIs in the third trimester of pregnancy. However, the risk of severe neonatal adaptation syndrome, which would require neonatal intensive care, is low. The association between SSRI exposure and persistent pulmonary hypertension of the newborn remains controversial, but the evidence suggests a weak relationship with this rare outcome. The decision to initiate an SSRI in pregnancy should be individualized. Providers caring for pregnant women using SSRIs should feel comfortable discussing possible neonatal adaptation syndrome associated with the antenatal use of SSRIs, with a primary focus on appropriate treatment of maternal depression after discussion of risks and benefits.

Safety of Selective Serotonin Reuptake Inhibitors in Pregnancy: A Review of Current Evidence.

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed antidepressant medications worldwide. However, over the past decade, their use during pregnancy, a period of extreme vulnerability to the onset of depression, has become highly concerning to patients and their healthcare providers in terms of safety to the developing fetus. Exposure to SSRIs in pregnancy has been associated with miscarriage, premature delivery, neonatal complications, birth defects-specifically cardiac defects-and, more recently, neurodevelopmental disorders in childhood, specifically autism spectrum disorders. Studies addressing the effect of individual SSRIs indicate a small but higher risk for birth defects with maternal fluoxetine and paroxetine use. Though the excess in absolute risk is small, it may still be of concern to some patients. Meanwhile, antenatal depression itself is associated with adverse perinatal outcomes, and discontinuing antidepressant treatment during pregnancy is associated with a high risk of relapse of depression. Whether the observed adverse fetal effects are related to the mother's medication use or her underlying maternal illness remains difficult to determine. It is important that every pregnant woman being treated with an SSRI (or considering such treatment) carefully weighs the risks of treatment against the risk of untreated depression for both herself and her child. The importance of recognizing a higher risk for the development of adverse outcomes lies in the potential for surveillance and possibly a timely intervention. Therefore, we recommend that pregnant women exposed to any SSRI in early pregnancy be offered options for prenatal diagnosis through ultrasound examinations and fetal echocardiography to detect the presence of birth defects. Tapering off or switching to other therapy in early pregnancy, if appropriate for the individual, may also be considered on a case-by-case basis.

Selective serotonin reuptake inhibitor use during pregnancy increases the risk of postpartum hemorrhage and anemia: a hospital‐based cohort study

Selective serotonin reuptake inhibitors (SSRIs) are known to increase the risk of gastrointestinal bleeding. Study the risk of bleeding-related complications in relation to SSRI in pregnancy. This was a hospital-based cohort study. All women who gave birth at Karolinska University Hospital in Stockholm over a 5-year period (2007 to 2011) were included in the study. Those women who the electronic maternal health record indicated were using SSRI (n = 500) were considered exposed, and all other women formed a control population (n = 39,594). The main outcome measures were blood loss, postpartum hemorrhage (PPH), PP anemia and length of hospitalization. The absolute risk of PPH and PP anemia for the 1.2% exposed to SSRI were 18.0% and 12.8%, respectively. Women with a vaginal non-surgical delivery who reported use of SSRI during pregnancy had approximately a 2-fold increased risk of both PPH (OR, 2.6; 95% CI, 2.0-3.5) and PP anemia (OR, 2.1; 95% CI, 1.5-2.9), as compared with controls. Blood loss and length of hospitalization were significantly higher among women using SSRI than non-users (arithmetic mean 484 mL vs. 398 mL, 3.8 days vs. 2.4 days, respectively). The use of SSRI during pregnancy increases blood loss and doubles the risk of PPH and PP anemia in a setting where SSRI had not been considered a risk factor for increased blood loss. Because PPH is a leading cause of maternal mortality and morbidity, the awareness of bleeding-related complications is important, both in relation to pregnancy and to surgery in general.

Bipolar Disorder and Pregnancy: Maintaining Psychiatric Stability in the Real World of Obstetric and Psychiatric Complications

This article describes complex, real-life issues faced by a woman with bipolar I disorder who wished to bear a healthy child while remaining psychiatrically well. The therapeutic issues include balancing treatment decisions that affect fetal and maternal risks. The authors address the importance of carefully considering the patient’s history of response to medications when evaluating risks to maternal and fetal health. They discuss the role of the psychiatrist as a part of the treatment team faced with unpredictable but not unexpected complexities, such as miscarriage, abnormal or questionable prenatal screening tests, gestational diabetes, and the emergence of fetal decelerations, preterm labor, and psychiatric decompensation. The article presents and evaluates treatment decisions made in the setting of multiple obstetric and psychiatric complications that do not clearly fit published algorithms. The importance of incorporating family and social supports as an integral part of the treatment plan is emphasized.

Parsing Risk for the Use of Selective Serotonin Reuptake Inhibitors in Pregnancy

Parsing Risk for the Use of Selective Serotonin Reuptake Inhibitors in Pregnancy

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

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

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

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

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

Estimates of the lifetime risk of major depression in women range from 10% to 25%, peaking during the reproductive years. Today, selective serotonin-reuptake inhibitors (SSRIs) are the most commonly used type of antidepressant medication. Recent studies suggest that taking these drugs while pregnant may be associated with birth defects in general and with congenital heart defects in particular. The investigators have analyzed data from 9622 case infants having major birth defects and 4092 control infants who were born in the years 1997 to 2002 and enrolled in the National Birth Defects Prevention Study. Both cases and controls were chosen through birth defects surveillance systems in 8 states. The mothers took part in a standardized phone interview dealing with exposure to potential risk factors, including medications, before and during pregnancy. Exposure was defined as taking any SSRI from 1 month before to 3 months after conception. Combining cases and control subjects, 3% of study participants reported having used a SSRI at some time before or during pregnancy, and 2.3% during the designated 4-month interval. No significant association was found between the maternal use of SSRIs during early pregnancy and congenital heart defects. There were, however, 3 conditions associated with maternal use of SSRIs. They included anencephaly (adjusted odds ratio [OR], 2.4; 95% confidence interval [CI], 1.1–5.1); craniosynostosis (OR, 2.5; 95% CI, 1.5–4.0); and omphalocele (OR, 2.8; 95% CI, 1.3–5.7). None of the mothers of case infants having defects associated with SSRI use were found to have been exposed at the same time to medications known to have teratogenic effects. This study failed to establish any association between the maternal use of SSRIs during early pregnancy and an elevated risk of congenital heart defects—or of several other classes of birth defects. Three associations were observed, but the absolute risks were small in view of the baseline risk of birth defects inherent in all pregnancies. At the same time, maternal stress and depression during pregnancy have been implicated in adverse reproductive outcomes, and discontinuing antidepressant therapy in pregnant women who are seriously depressed may negatively affect both the mother and infant.

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.

The Use of Selective Serotonin Reuptake Inhibitors in Pregnancy

Objective: To provide an update of literature on the safety of using selective serotonin reuptake inhibitors (SSRIs) during pregnancy.Methods: MEDLINE was searched for English-language papers published from 1985 to 2003 on human studies of SSRIs, using the key words “serotonin reuptake inhibitors,” “citalopram,” “fluoxetine,” “fluvoxamine,” “paroxetine,” and “sertraline”Results: The literature search yielded 12 338 publications. Previous studies on the safety of SSRIs in pregnancy were often based on small samples from medical centres, with heterogeneous design and outcome ascertainment methods, and had yielded inconsistent results. Consequently, the management of pregnant women with depression poses challenges to clinicians who are hesitant to prescribe anti-depression drugs, including SSRIs, because of concern about potential risks to the fetuses. Failure to adequately treat maternal depression can lead to progressively worsening depression that greatly compromises maternal-fetal health and can impair bonding and childcare in the postpartum period.Conclusions: Because of the uncertainty regarding the safety of SSRI use during pregnancy, consultation with specialists experienced in treating depression may be helpful when treating pregnant women with SSRIs. Large-scale, population-based studies to comprehensively assess the safety of SSRIs in pregnancy are needed.

Treatment of Depression in Women: A Summary of the Expert Consensus Guidelines

Women constitute two-thirds of patients suffering from common depressive disorders, making the treatment of depression in women a substantial public health concern. However, high-quality, empirical data on depressive disorders specific to women are limited, and there are no comprehensive evidence-based practice guidelines on the best treatments for these illnesses. To bridge the gap between research evidence and key clinical decisions, the authors developed a survey of expert opinion concerning treatment of four depressive conditions specific to women: premenstrual dysphoric disorder, depression in pregnancy, postpartum depression in a mother choosing to breast-feed, and depression related to perimenopause/menopause. The survey asked about 858 treatment options in 117 clinical situations and included a broad range of pharmacological, psychosocial, and alternative medicine approaches. The survey was sent to 40 national experts on women's mental health issues, 36 (90%) of whom completed it. The options, scored using a modified version of the RAND Corporation's 9-point scale for rating appropriateness of medical decisions, were assigned one of three categorical rankings-first line/preferred choice, second line/alternate choice, third line/usually inappropriate-based on the 95% confidence interval of each item's mean rating. The expert panel reached consensus (defined as a non-random distribution of scores by chi-square "goodness-of-fit" test) on 76% of the options, with greater consensus in situations involving severe symptoms. Guideline tables indicating preferred treatment strategies were then developed for key clinical situations. The authors summarize the expert consensus methodology they used and then, for each of the four key areas, review the treatment literature and summarize the experts' recommendations and how they relate to the research findings. For women with severe symptoms in each area we asked about, the first-line recommendation was antidepressant medication combined with other modalities (generally psychotherapy). These recommendations parallel existing guidelines for severe depression in general populations. For initial treatment of milder symptoms in each situation, the panel was less uniform in recommending antidepressants, and either gave equal endorsement to other treatment modalities (e.g., nutritional or psychobehavioral approaches in PMDD; hormone replacement in perimenopause) or preferred psychotherapy over medication (during conception, pregnancy, or lactation). In all milder cases, however, antidepressants were recommended as at least second-line options. Among antidepressants, selective serotonin reuptake inhibitors (SSRIs) were recommended as first-line treatment in all situations. The specific SSRIs that were preferred depended on the particular clinical situation. Tricyclic antidepressants were highly rated alternatives to SSRIs in pregnancy and lactation. In evaluating many of the treatment options, the experts had to extrapolate beyond controlled data in comparing treatment options with each other or in combination. Within the limits of expert opinion and with the expectation that future research data will take precedence, these guidelines provide some direction for addressing common clinical dilemmas in women, and can be used to inform clinicians and educate patients regarding the relative merits of a variety of interventions.

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.

Use of New SSRIs in Pregnancy Appears Safe.

The selective serotonin reuptake inhibitors (SSRIs) dominate treatment of depression. In a recent study, use of the SSRI fluoxetine during pregnancy

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.