Depression in Pregnant Adolescents: Considerations for Treatment

Pregnancy in adolescents continues to be a major public health concern in the US. Depression in adolescent females, is also a major health concern. Adolescence is a time of rapid metabolic, hormonal, physiologic, and developmental changes, and when the physiologic and psychological changes that occur during pregnancy are superimposed upon normal developmental changes, a complex medical picture may emerge which can include depressive symptomatology. Treating depression in the pregnant adolescent is complex due to the concerns about the use of selective serotonin reuptake inhibitors (SSRIs) in any pregnant woman, the fact that only one SSRI (fluoxetine) is FDA-approved for depression in the pediatric population, the concern over the black box warning for antidepressants in the pediatric population, and the reality that untreated depression in pregnancy has been shown to be associated with poor outcomes for both mother and baby. This article discusses these concerns and provides some recommendations/considerations for treatment of depression in pregnant adolescents.     

The Use of Selective Serotonin Reuptake Inhibitors in Pregnancy and Lactation: A Review

The selective serotonin reuptake Inhibitor (SSRI) type of antidepressants which include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), and fluvoxamine (Luvox), are valued for their efficacy, safety and side effect profile when prescribed to treat depression and co-morbid anxiety disorders. However, when a pregnant or nursing mother becomes depressed, treatment with the SSRIs is controversial because conflicting findings have been reported in the literature. A paucity of data exists on this subject. This could partly be because many women refuse medication however severe their illness may be. Another reason for the scarcity of research could be because the treating physician may not feel at ease administering these medicines in the light of insufficient information on the topic. Consequently, several crucial questions remain unanswered, the most important of them being the long-term neurodevelopmental effect of these medicines on the growing infant. The SSRIs travel through the placenta and breast milk and can be measured in the infants’ serum. The U.S. Food and Drug Administration or the Health Protection Branch of Canada has not yet approved SSRIs for use in pregnancy and lactation. This contradiction further adds to the dilemma of the treating physician of whether or not to prescribe SSRIs to pregnant and nursing women. This article reviews the use of SSRIs in pregnmuy and lactation.     

Use of selective serotonin reuptake inhibitors during pregnancy and disorganised infant–mother attachment

Objective: To examine the quality of infant–mother attachment in a prospective case series of infants whose mothers took selective serotonin reuptake inhibitors (SSRIs) during pregnancy. Background: SSRIs are prescribed to 2–6% of pregnant women. Recent articles on the use of SSRIs during pregnancy note the increased risk for problematic infant–mother relationships among mothers with untreated postpartum depression. However, little is known about the quality of infant–mother relationships among mothers who took SSRIs during pregnancy. Methods: Five mothers who took SSRIs during pregnancy were recruited from a community study of infant development. Mothers completed ratings of postpartum depression symptoms (Beck Depression Inventory) 4–6 times between 1 month and 1 year following the infant’s birth. At 1 year postpartum, quality of infant–mother attachment was assessed using the strange situation procedure. Results: Four of the five infant–mother dyads (80%) were classified as disorganised, a rate considerably higher than in postpartum depression samples. Conclusion: These results are used to raise questions about the clinical implications of research on in utero exposure to SSRIs, perinatal depression, and disorganised attachment. Specifically, this case series raises questions about using research on the link between postpartum depression and infant–mother attachment as a rationale for the use of SSRIs during pregnancy. Current research indicates use of SSRIs during pregnancy may: (1) increase risk for disorganised attachment, (2) decrease risk for disorganised attachment, or (3) have no effect on disorganised attachment.     

Fetal and neonatal effects of maternal drug treatment for depression

Depression has a female sex predilection with 2 to 3% of the pregnant women population presently requiring treatment with selective serotonin reuptake inhibitors (SSRI). Exposure to SSRIs in late gestation leads to clinical manifestations in as much as 30% of the neonates. These include neurobehavioral, respiratory, gastrointestinal, and somatic symptoms. Among the respiratory manifestations, persistent pulmonary hypertension syndrome is a newly recognized and concerning side effect of SSRI exposure in utero. This causal association has been reproduced in an animal model where fluoxetine administration to pregnant rats induces fetal pulmonary hypertension. The pharmacological effects of SSRI on the fetus and newborn, available treatment, and prevention strategies are discussed in this review.     

Maternal corticotropin-releasing hormone and the use of selective serotonin reuptake inhibitors independently predict the occurrence of preterm birth

Introduction: Studies support the premise that chronic maternal stress may trigger a premature sequence of physiologic events ending in preterm birth (PTB). Furthermore, chronic stress is highly correlated with depression and anxiety, which also are associated with PTB. However, some studies report that medication status rather than depression and/or anxiety may reflect the risk for PTB. Although the purpose of this small, preliminary study was to evaluate the association between chronic maternal stress and PTB, this report focuses on the unexpected finding of the association between maternal use of selective serotonin reuptake inhibitors (SSRIs) and PTB. Methods: A prospective cohort study of 100 pregnant women included measures of contributors to chronic maternal stress and corticotropin‐releasing hormone (CRH). Demographic and behavioral data included smoking, substance use, and use of medications for depression and anxiety. Results: Pregnant women who used SSRIs to treat depression and/or anxiety were nearly 12 times more likely to give birth before term when compared with women who did not use these medications. Women with CRH levels in the fourth quartile were 6 times more likely to give birth before term when compared with women whose CRH levels were in the lower 3 quartiles. No associations were found between SSRI use and CRH levels. Discussion: Associations between PTB and maternal use of SSRIs are not understood. It is important not to alter current approaches to the treatment of depression and anxiety without thorough discussion with women regarding the potential benefits and harms of various treatment options.     

Risks associated with selective serotonin reuptake inhibitors in pregnancy

OBJECTIVE: To study the effects of selective serotonin reuptake inhibitors (SSRIs) on pregnancy outcome. METHODS: We performed a population-based study of women exposed to SSRIs during pregnancy (n = 1782). Data were derived from a national project in Finland, established by 3 governmental organizations. In that project, the Drug Reimbursement Register, the Medical Birth Register, the Register of Congenital Malformations, and the Register of Induced Abortions have been linked. Comparisons were made between women with SSRI purchases to matched controls and between women with purchases in different trimesters. Only singleton pregnancies were included. Primary outcomes were major malformations, preterm birth, small for gestational age, low birth weight, and treatment in neonatal special or intensive care unit. Analyses were based on logistic models. RESULTS: Major malformations were not more common in infants or fetuses of women with first trimester SSRI purchases (n = 1,398) when compared with controls with no drug purchases (P = .4). Of infants born to mothers with SSRI purchases in the 3rd trimester, 15.7% were treated in special or intensive care unit compared with 11.2% of infants exposed only during the 1st trimester (P = .009, adjusted odds ratio 1.6, 95% confidence interval 1.1-2.2). We found no increased risk of preterm birth (< 37 weeks), birth 32 weeks of gestation or less, small for gestational age, or low birth weight in women with purchases in each trimester or during the 2nd and 3rd trimesters when compared with women with only 1st trimester purchases. CONCLUSION: Use of SSRIs during pregnancy is not independently associated with increased risk of adverse perinatal outcome other than need for treatment in neonatal special or intensive care unit.     

Making Sense Out of the Controversy: Use of SSRIs in Pregnancy

Perinatal depression complicates up to 20 % of all pregnancies. Selective serotonin reuptake inhibitor (SSRI) drugs have become the first-line treatment of depressive symptoms during pregnancy. About 7.5 % of all pregnancies are currently exposed to psychotropic medications. Recent studies suggest the SSRI medications may have some detrimental effects in pregnancy, including a possible increased risk of miscarriage, preterm delivery, clubfoot, heart defects, brain and craniofacial abnormalities, persistent pulmonary hypertension of the newborn, neonatal seizures, low neonatal Apgar score, as well as neurodevelopmental and behavioral changes. Patients and healthcare providers should take into consideration all the possible known negative effects of untreated depression during pregnancy, but also the possible fetal risks associated with the use of SSRIs.     

Advanced neuroimaging: A window into the neural correlates of fetal programming related to prenatal exposure to maternal depression and SSRIs

Fetal programming is a conceptual framework whereby the in utero environment shapes the offspring's neurodevelopment. Maternal depression and treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants during pregnancy are common prenatal exposures that affect critical early life developmental programming processes. Prenatal depression and SSRIs both have been reported to increase the risks for preterm birth, low birth weight, and are associated with behavioral disturbances across the early life span. However, not all exposures lead to adverse developmental outcomes and distinguishing how each exposure contributes to variations in development remains challenging. Advances in neuroimaging, using MR and EEG, offer novel insights into central processes that might reveal the neural correlates of fetal programming. This review focuses on emerging findings from neuroimaging studies reflecting early brain functional and structural development associated with prenatal exposure to maternal depression and SSRI antidepressants. Suggestions for future research directions that use neuroimaging as a tool to advancing our understanding of the early origins of developmental plasticity are offered.     

Paroxetine withdrawal syndrome as differential diagnosis of acute neonatal encephalopathy?

Paroxetine, a selective serotonin reuptake inhibitor (SSRI) may be given in severe cases of maternal depression and panic disorders during pregnancy. However, it may lead to severe withdrawal symptoms: respiratory distress, jitteriness, convulsions, hypoglycaemia, an impaired muscle tone and necrotising enterocolitis. These symptoms, also called neonatal withdrawal syndrome, may last up to one month. We report a girl born at 37 weeks of gestation presenting 12 hours after birth with hypopnea, bradycardia and a decreased muscular tone of unknown origin. The child was transferred to the NICU and was intubated and ventilated mechanically. Within the first days the patient also developed cerebral seizures. The EEG showed severe abnormalities. Later we learned that the patient's mother had been treated with Paroxetine during pregnancy. The patient recovered after two days of ventilation and anticonvulsive medication with phenobarbital. The EEG result showed a siginificant improvement. At day 10 she was discharged in good condition. Recognition and treatment of the presented neonatal problems could have been more effective and faster, if the attending pediatricians had been informed earlier about the maternal medication with SSRIs. Neonates of mothers who were treated with SSRIs during pregnancy should be monitored. Paroxetine withdrawal syndrome should be considered as one of the differential diagnosis of neonatal encephalopathy.     

Antidepressant use during pregnancy: the benefit-risk ratio

Antidepressants are used commonly in pregnancy. Physicians who provide health care for pregnant women with depression must balance maternal well-being with potential fetal risks of these medications. Over the last decade, scores of original and review articles have discussed whether selective serotonin reuptake inhibitors-selective serotonin norepinephrine reuptake inhibitors possess risks to the fetus; however, very little has been done to integrate these potential risks, if they exist, into an overall context of a benefit:risk ratio. This review aims at presenting an updated analysis of fetal and maternal exposure to selective serotonin or norepinephrine reuptake inhibitors to allow an evidence-based benefit:risk ratio. When a psychiatric condition necessitates pharmacotherapy, the benefits of such therapy far outweigh the potential minimal risks of cardiac malformations, primary pulmonary hypertension of the newborn infant, or poor neonatal adaptation syndrome.     

Selective serotonin reuptake inhibitors for premenstrual syndrome and premenstrual dysphoric disorder: a meta-analysis

OBJECTIVE: To systematically review evidence of the treatment benefits of selective serotonin reuptake inhibitors (SSRIs) for symptoms related to severe premenstrual syndrome (PMS) and premenstrual dysphoric disorder. DATA SOURCES: We conducted electronic database searches of MEDLINE, Web of Science, Cochrane Library, Embase, PsycINFO, and Cinahl through March 2007, and hand-searched reference lists and pertinent journals. METHODS OF STUDY SELECTION: Studies included in the review were double-blind, randomized, controlled trials comparing an SSRI with placebo that reported a change in a validated score of premenstrual symptomatology. Studies had to report follow-up for any duration longer than one menstrual cycle among premenopausal women who met clinical diagnostic criteria for PMS or premenstrual dysphoric disorder. From 2,132 citations identified, we pooled results from 29 studies (in 19 citations) using random-effects meta-analyses and present results as odds ratios (ORs). TABULATION, INTEGRATION, AND RESULTS: Our meta- analysis, which included 2,964 women, demonstrates that SSRIs are effective for treating PMS and premenstrual dysphoric disorder (OR 0.40, 95% confidence interval [CI] 0.31-0.51). Intermittent dosing regimens were found to be less effective (OR 0.55, 95% CI 0.45-0.68) than continuous dosing regimens (OR 0.28, 95% CI 0.18-0.42). No SSRI was demonstrably better than another. The choice of outcome measurement instrument was associated with effect size estimates. The overall effect size is smaller than reported previously. CONCLUSION: Selective serotonin reuptake inhibitors were found to be effective in treating premenstrual symptoms, with continuous dosing regimens favored for effectiveness.     

Breastfeeding among women exposed to antidepressants during pregnancy

This prospective cohort study compares the breastfeeding outcomes of women exposed to selective serotonin reuptake inhibitor (SSRI) antidepressants at the time of delivery, those who discontinued use prior to delivery, and those not exposed. Participants include 466 pregnant women who enrolled in the California Teratogen Information Service Clinical Research Program (CTIS) over 10 years. In bivariate analyses, breastfeeding rates were significantly different across SSRI exposure groups, with unexposed women having the highest rates. We used logistic regression to examine the relationship between SSRI exposure and breastfeeding outcomes. After adjustment for potential confounders, those exposed to an SSRI both prior to delivery (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.20-0.94) and at the time of delivery (OR, 0.34; 95% CI, 0.16-0.72) were significantly less likely to initiate breastfeeding as compared to unexposed women. Women exposed to an SSRI during pregnancy appear to be at risk for poorer breastfeeding outcomes and may benefit from additional education and support.     

Depression and pregnancy: Use of selective serotonin reuptake inhibitors in pregnancy

Treatment of depression must address somatic complaints (when they exist) and the depression, and when treating women of childbearing age, choice of antidepressant therapy must be based not only on ease of use and lack of side effects, but also on possible effects on the fetus. From a standpoint of toxicity and risk of overdose, selective serotonin reuptake inhibitors (SSRIs) appear to have an advantage and have achieved widespread use. Limited data are available with regard to effects of this class of agents on the developing fetus. Women who called the Pregnancy Safety Hotline during a 17-month period of study were followed prospectively after their inquiry about Prozac, Paxil, and Zoloft. Data were obtained by telephone interview, and birth defects were confirmed by calling the pediatrician with the consent of the mother. In the study period, a total of 2,819 calls were made to the Pregnancy Safety Hotline; 105 (3.7%) of the calls were made by women exposed to SSRIs during pregnancy; 39 (37.1%) were available and consented to a telephone interview during the preliminary study period. In this group there were 6 spontaneous abortions, 6 elective terminations, 6 continuing pregnancies, and 21 delivered infants, No major birth defects were noted; two minor birth defects were found, and a trend was observed for slightly decreased birth weight with increasing duration of treatment. These findings are consistent with previous reports indicating no increase in major malformation rate and a possible slight association with decreased birth weight with longer duration of exposure, but additional data are needed.     

Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and effects on the fetus and newborn: a meta-analysis.

Selective serotonin reuptake inhibitors (SSRIs) are frequently used to treat depression during pregnancy and the postpartum period. These drugs are capable of crossing the placenta and being transferred to the newborn during lactation. This report reviews the available information regarding the effects of SSRIs on the fetus and newborn; including long-term neurodevelopmental outcomes.     

Do Maternal Pharmacogenetics Impact the Neonatal Abstinence Syndrome Following In Utero Exposure to Antidepressant Medications?

ObjectiveSelective serotonin reuptake inhibitors (SSRIs) and serotonin–norepinephrine reuptake inhibitors (SNRIs) are the most commonly used medications for mood and anxiety disorders in women. Many women need to continue or initiate these medications during pregnancy, but there is concern about potential withdrawal effects in the newborn, referred to as neonatal abstinence syndrome (NAS). The reason why some infants remain asymptomatic while others are affected has not been elucidated. The objective of this study was to examine whether genetic differences in maternal drug metabolism influence the incidence of NAS.MethodsWomen who took Selective serotonin reuptake inhibitors s/SNRIs during pregnancy were recruited from obstetrical clinics. DNA was extracted from saliva samples for genetic analyses of cytochrome P450 (CYP) enzyme polymorphisms. Delivery and NAS data were collected from electronic medical records.ResultsNinety-five women participated. The overall NAS rate was 16.2%. Mild NAS was seen in 13.8% of neonates and severe NAS, in 2%. One-quarter (25%) of the neonates with mild withdrawal symptoms were born to mothers with polymorphisms associated with slower metabolism of their particular antidepressant, but this association was not statistically significant.ConclusionImportantly, the overall rate of NAS in our study was lower than previously reported. Maternal CYP polymorphisms did not affect the rate of NAS in neonates exposed to SSRIs/SNRIs in utero. This study lends added assurance to patients requiring SSRIs or SNRIs during pregnancy.     

Sertraline alters multidrug resistance phosphoglycoprotein activity in the mouse placenta and fetal blood-brain barrier

Phosphoglycoprotein (P-gp) is highly expressed in the placental syncytiotrophoblast and prevents xenobiotics from entering the fetus. In tumor cells, P-gp-mediated substrate efflux is inhibited by selective serotonin reuptake inhibitors (SSRIs). However, nothing is known regarding the effects of SSRIs on P-gp function in the placenta or fetal tissues. We hypothesized that the SSRI sertraline would decrease P-gp-mediated drug efflux at the placenta and fetal blood-brain barrier (BBB)-increasing P-gp substrate transfer from the mother to the fetus and fetal brain. In contrast to our hypothesis, this study presents the novel findings that sertraline (4 hours exposure) increases placental P-gp-mediated efflux (P < .001), resulting in decreased drug transfer to the fetus. Meanwhile, sertraline decreases fetal (P < .001) and maternal (P < .05) BBB P-gp-mediated efflux, resulting in increased drug transfer into the fetal and maternal brain from the circulation. This suggests that P-gp regulation by sertraline is tissue specific. These findings have important clinical implications with respect to fetal protection during maternal drug therapy in pregnancy.     

Psychic disturbances in the postpartum period: an increasing problem?

Postpartum psychic disorders can be mainly divided into 3 groups: The so-called postpartum blues, the postpartum depression and the postpartum psychosis. The postpartum blues occurs 3 - 5 days postpartum in 50 - 70 % of deliveries mostly disappearing after one week without specific therapy. However, 20 - 30 % of patients will develop a depression in their further postpartum course so that a thorough evaluation concerning depression is warranted, if blues symptoms persist more than 2 weeks. Postpartum depression can be found in 10 - 15 % of deliveries and mostly occurs several weeks or months after delivery with symptoms of depressive mood, sleeping disorders, anxiety, loss of interest and accord and feelings of guilt up to suicidal ideas. In order not to misinterpret them as postpartum blues specific questions concerning the mood of the young mother during the postpartum examination - if necessary using the Edinburgh scale - are recommended. In patients with known risk factors for a postpartum depression (i. e. postpartum depression or psychosis in previous pregnancies, depression disorder, anxiety disorder, bipolar illness), a thorough survey is mandatory and - if necessary - a prophylactic treatment in cooperation with the psychiatrist. Less severe forms of postpartum depression can mostly be treated with psychotherapy and sociotherapy on an outpatient basis. In more severe cases, antidepressant drugs (selective serotonin reuptake inhibitors, SSRIs or some tricyclic drugs) are indicated. Postpartum anxiety and compulsive disorders respond well to psychotherapy; besides in anxiety disorders benzodiazepines are recommended, in compulsive disorders SSRIs. Postpartum psychoses (about 0.1 - 0.2 %) most often occur in bipolar or schizoaffective disorders or after postpartum psychosis. They require a hopitalization mainly because of the danger of suicide and homicide toward the newborn; ideally this is performed in mother-child-units.     

Birth outcomes after prenatal exposure to antidepressant medication

OBJECTIVE: The purpose of this study was to examine prospectively the incidence of congenital anomalies and neonatal complications after prenatal exposure to antidepressant medication. STUDY DESIGN: Birth outcomes were obtained from a review of obstetric and neonatal records of 138 women who were treated with selective serotonin reuptake inhibitor antidepressant medications (SSRIs) during pregnancy. RESULTS: The incidence of congenital anomalies in this study was 1.4%, comparable to general population rates. Rates of low birth weight and preterm births were low, occurring in 2.9% and 6.5% of births, respectively. The low birth weight infants had been exposed to relatively high doses of fluoxetine (40-80 mg/d) throughout pregnancy. Average maternal weight gain in pregnancy was comparable across the three major medication categories (fluoxetine, paroxetine, sertraline). CONCLUSION: After prenatal use of selective serotonin reuptake inhibitor antidepressant medications, neonatal complications and congenital anomalies appear to occur within general population rates. However, maternal use of high doses of fluoxetine throughout pregnancy may be associated with a risk for low birth weight.