Rita Suri

Hormonal Changes in the Postpartum and Implications for Postpartum Depression

The months following childbirth are a time of heightened vulnerability to depressive mood changes. Because of the abrupt and dramatic changes occurring in hormone levels after delivery, many studies have examined the role of hormonal factors in postpartum depression. The authors review the literature on potential hormonal etiologies in postpartum depression, in particular for progesterone, estrogen, prolactin, cortisol, oxytocin, thyroid, and vasopressin. While evidence for an etiologic role is lacking for most hormones, changes in certain hormonal axes may contribute to depressive mood changes in some women following childbirth.

The impact of depression and fluoxetine treatment on obstetrical outcome

SummaryIntroduction: This study prospectively followed women over the course of pregnancy to assess the impact of depression and/or antidepressant treatment on obstetrical outcome.Method: Sixty-four outpatient women with an Axis I diagnosis of major depressive disorder or no psychiatric history were followed in each trimester of pregnancy with administration of the CES-D. A subset of the women with depression received treatment with fluoxetine during pregnancy. Subjects with a CES-D score greater than 16 at any time point were further assessed for the presence of an active major or minor depressive episode. Primary outcome variables included infant gestational age, birth weight, Apgar score, and admission to the neonatal intensive care unit.Results: Analyzable data were available for 62 women. No significant differences were found in outcome variables between those women with exposure to medication and/or prenatal depressed mood and those women without a history of depression.Conclusions: In contrast to other studies, our study did not demonstrate an adverse effect of fluoxetine exposure per se on obstetrical outcome. In addition, we did not find a significant impact of depression during pregnancy on obstetrical outcome.

Bupropion-Sustained Release as a Treatment for SSRI-Induced Sexual Side Effects

Twenty-four subjects treated with serotonin reuptake inhibitors for a depressive disorder who had new-onset sexual side effects coincident with antidepressant treatment were treated with escalating doses of bupropion SR up to 300 mg daily for 7 weeks. Global response rates were 46% for women and 75% for men. All sexual side effects improved in response to bupropion SR in both men and women with no differential effect on any one sexual side effect. Most of the improvement (more than 50%) occurred within the first 2 weeks and at low dose (100-200 mg/day). When prescribed in an open fashion, bupropion SR appeared to be effective in treating all the major categories of sexual side effects.

Estimates of nursing infant daily dose of fluoxetine through breast milk

BACKGROUND This study compared three methods of estimating the daily dose of fluoxetine to nursing infants and the relationship between these estimates and infant serum concentrations. METHODS Breast milk and infant serum concentrations of fluoxetine and norfluoxetine were obtained from 10 nursing mother-infant pairs. Quantification of daily infant dose was determined by three methods: 1) collection of the total volume of breast milk over 24 hours and determination of the average breast milk concentration (Babys Total Daily Dose); 2) determination of the maximum and minimum breast milk concentrations during 24 hours and an estimated milk consumption of 150 mL/kg/day (Atkinson Model); and 3) determination of the gradient of excretion of medication into breast milk at a specified time after the maternal dose, applying this gradient to each nursing collection and summing the values for 24 hours (Mathematical Model). The relationship between the 24-hour medication dose, obtained from each method, and the infant serum concentrations was examined. RESULTS A total of 177 breast milk and 10 infant serum samples were collected. An estimate of the infant daily medication dose obtained by the Mathematical Model was the best predictor of total infant serum concentration. CONCLUSIONS Breast milk analysis may allow one to determine whether medication concentrations will be detectable in an infant, eliminating the need for an infant serum concentration. Although the Mathematical Model seems to reflect infant serum concentration most accurately, all three methods suggest that the maximum dose that a nursing child receives over the course of a year equals as much as 120 mg, or 160 +/- 47% of the maternal daily dose.

Acute and long-term behavioral outcome of infants and children exposed in utero to either maternal depression or antidepressants: a review of the literature

OBJECTIVE The authors reviewed the published literature on the acute and long-term neurobehavioral effects on infants and children of either in utero exposure to maternal depression or in utero exposure to antidepressants. DATA SOURCES The PubMed electronic database was searched to locate 292 English-language studies from the first available year to October 2013 using the keywords pregnancy, antidepressants, depression, perinatal, and neurobehavioral. STUDY SELECTION The authors reviewed only prospective studies that assessed the impact of maternal depression during pregnancy or maternal antidepressant treatment during pregnancy on (1) clearly defined short-term behavioral outcomes in infants (perinatal outcome) or (2) longer-term behavioral outcomes in infants and children (neurodevelopmental outcome). DATA EXTRACTION Studies were included if they were prospective and assessed the impact of maternal depression or maternal antidepressant treatment during pregnancy on clearly measurable, objective short-term and longer-term behavioral outcomes in infants and children. RESULTS Untreated depression during pregnancy is associated with short-term neonatal effects, including increased distress after delivery, less than optimal orientation and motor activity, and disrupted sleep. Longer-term effects on neurobehavioral outcome have also been reported, including disruptive social behavior, depression, and changes in the period of sensitivity for language discrimination. Antidepressant exposure during pregnancy is associated with adverse short-term perinatal symptomatology, including effects on autonomic and motor activity, habituation, and sleep. Longer-term studies of neurobehavioral outcomes of in utero antidepressant exposure suggest potential effects on gross motor function and language development but not cognition. CONCLUSIONS In utero exposure to either maternal depression or antidepressants carries risks to the developing fetus. Treatment decisions regarding whether and how to treat depression during pregnancy must be made on an individual basis, with careful consideration of the impact of these decisions on both mother and infant.

A Prospective, Naturalistic, Blinded Study of Early Neurobehavioral Outcomes for Infants Following Prenatal Antidepressant Exposure

OBJECTIVE This study examined the potential effects of antidepressant exposure in pregnancy on early infant neurobehavioral outcomes. METHOD In this prospective, naturalistic study, neurobehavioral assessments using the Brazelton Neonatal Behavioral Assessment Scale (BNBAS) were completed by blinded raters between March 2001 and August 2005 on 64 infants who were born to mothers in 1 of 3 categories: (1) women with a history of DSM-IV-diagnosed major depressive disorder (MDD) who were treated with antidepressants during pregnancy, (2) women with a history of DSM-IV-diagnosed MDD who discontinued or chose not to be treated with antidepressants during pregnancy, and (3) a nonpsychiatric control group. Summary scores for the BNBAS were obtained within the first week of life and at 6 to 8 weeks of age. RESULTS No significant differences were observed between groups at either the first week after delivery or at 6 to 8 weeks of age on any of the summary scores for the 7 major clusters of the BNBAS. CONCLUSIONS Antidepressant exposure during pregnancy does not appear to have major adverse effects on indices of early infant neurobehavioral development during the first 2 months of life as assessed by the BNBAS. While this finding is encouraging, further studies with larger samples and longer follow-up are needed.

The Pregnancy Depression Scale (PDS): a screening tool for depression in pregnancy

Depression in pregnancy can be underdiagnosed as a consequence of the symptoms being misattributed to “normal pregnancy.” There are currently no validated clinician-rated scales that assess for depression specifically during pregnancy. We sought to develop a brief, convenient screening tool to identify depression in pregnant women in the community setting. Prospective mood data using the 28-item Hamilton Depression Rating Scale (HDRS) were collected monthly in 196 pregnant women with a history of a major depressive disorder. These data were analyzed to delineate those HDRS items associated (elevated) with normal pregnancy vs. those indicative of a pregnant woman meeting diagnostic criteria for a major depressive episode. Endorsement of symptoms on seven items of the HDRS were highly predictive of having a major depressive episode during pregnancy. We present a well-validated, brief scale to screen pregnant women for clinical depression. Whether this study will generalize to women who do not have a history of major depression remains to be studied.

Saliva Estriol Levels in Women with and Without Prenatal Antidepressant Treatment

BACKGROUND Prenatal antidepressant use has been associated with shorter pregnancy duration and an increased risk for preterm birth. This study measured saliva levels of estriol, a hormone that increases exponentially in the few weeks before spontaneous labor, in pregnant women with and without antidepressant treatment. METHODS Saliva estriol levels were obtained across the day at three time points during pregnancy in 77 subjects with a history of DSM-IV major depressive disorder (MDD) who were treated with antidepressants in pregnancy (Group 1), a history of DSM-IV MDD who were not treated or had limited exposure to antidepressants during pregnancy (Group 2), and a normal control group (Group 3). RESULTS Mean estriol levels in the second half of pregnancy were significantly higher for Group 1 (history of MDD, on meds) than Group 2 (history of MDD, off meds) or Group 3 (control). CONCLUSIONS Prenatal antidepressant use was associated with significantly higher saliva estriol levels in the second half of pregnancy. Whether estriol reflects a causal mechanism by which women on antidepressants have shorter pregnancy duration remains to be further studied.

Nefazodone for the treatment of postpartum depression

Antidepressant treatment studies for postpartum depression are limited to four for the SSRI’s (Appleby et al., 1997; Stowe et al., 1995; Suri et al., 2001; Misri et al., 2004), one for venlafaxine (Cohen et al., 2001) and one for bupropion (Nonacs et al., 2005). Women who suffer from postpartum depression often experience considerable anxiety (Hendrick et al., 2000). Cohen et al. (2001) suggest that reducing anxiety associated with postpartum depression may ‘‘catalyze’’ the response to antidepressant treatment. Nefazodone, a 5-HT receptor antagonist and reuptake blocker, has been shown to be effective in the treatment of depression with significant anxiety (Taylor and Prather, 2003) and may be beneficial in this unique population. We describe an eight week, open label trial of nefazodone for four women with postpartum depression and comorbid anxiety symptoms. This trial was conducted at the University of California at Los Angeles Neuropsychiatric Institute and was reviewed and approved by the institutional review board (IRB). Written informed consent was obtained in a manner approved by the IRB for subjects who participated. Inclusion criteria included outpatients between 18 and 45 years of age with a SCID confirmed diagnosis of depression in the first eight postpartum weeks, a score of 12 on the Edinburgh Postnatal Depression Scale, and a score of 14 on the Hamilton Anxiety Rating Scale. Due to the lack of data regarding the safety of nefazodone in nursing infants and a case report of drowsiness in a preterm breastfed infant (Yapp et al., 2000), breast feeding women were excluded from the study. Subjects began nefazodone treatment, 50 mg BID, and were followed weekly with clinical interviews and administration of the Ham-A and Ham-D by a blind rater. Nefazodone was titrated up to a maximum dose of 500 mg=day, as tolerated, over the first two study weeks. On entry, the mean Hamilton Anxiety (Ham-A) and Hamilton Depression (Ham-D) Rating Scale scores were 17.0 4.1 and 18.3 3.2, respectively. The mean final dose of nefazodone was 400 81.7 mg=day. One patient discontinued the study after week 4 due to lethargy (at a dose of 300 mg=day). All three remaining subjects showed improvement each week and obtained remission of anxiety (Ham-A scores of 3, 0, and 1) and depression (Ham-D scores of 3, 3, and 0) by the fifth week of the study. This remission persisted through week 8, the study endpoint. Our findings add to the limited literature on postpartum depression and suggest that nefazodone may be effective for women with postpartum depression accompanied by anxiety. Future larger double-blind, placebo-controlled studies are needed to determine if nefazodone is an effective treatment for this unique population. This study was funded in part by an unrestricted educational grant from Bristol-Myers Squibb.

The Assessment and Treatment of Postpartum Psychiatric Disorders

The authors discuss the importance of early identification and treatment of postpartum disorders. They then review the assessment, clinical characteristics, and psychotherapeutic and psychopharmacologic treatment of four major types of postpartum psychiatric conditions: postpartum blues, postpartum