Telephone-Based Depression Care Management for Postpartum Women: A Randomized Controlled Trial.

OBJECTIVE: With a period prevalence of 21.9% in the year after birth, depression is a common complication of childbearing. We assessed the impact of telephone-delivered depression care management (DCM) on symptom levels, health service utilization, and functional status 3, 6, and 12 months postpartum. METHODS: The randomized controlled trial was conducted at the University of Pittsburgh, Pittsburgh, Pennsylvania, from March 2006 through September 2010. Women (N = 628) who screened positive for depression (a score of 10 or greater on the Edinburgh Postnatal Depression Scale) 4 to 6 weeks postpartum were evaluated with the Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition With Psychotic Screen and enrolled in a randomized trial of DCM compared to enhanced usual care (EUC). Clinicians conducted telephone contacts to educate, assist with treatment decisions, monitor symptoms, facilitate access to services, and encourage links to community resources. Independent evaluators collected symptom scores, functional status, and health services use at 3, 6, and 12 months postpartum. Primary outcome was reduction of symptoms as measured by the Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement. RESULTS: Mean depressive symptom and function scores significantly improved (by greater than 50%) in both groups of women but did not differ by DCM versus EUC assignment. Health services use was similar in women randomly assigned to DCM compared to EUC. Women with childhood sexual abuse responded significantly more favorably to DCM on depression and functional measures (all P values < .02). CONCLUSIONS: Both DCM and EUC favorably impacted depression symptom levels and function. The subgroup of women with childhood sexual abuse benefited significantly more from DCM compared to the EUC condition. Regular telephone availability of a clinician is a resource that appears to be particularly therapeutic to women with childhood sexual abuse. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00282776.

Mood symptoms in pregnant and postpartum women with bipolar disorder: a naturalistic study.

OBJECTIVE: We conducted a prospective naturalistic study of pregnant women with bipolar disorder (BD) to evaluate symptoms of BD across childbearing and assess whether pharmacotherapy reduced their severity. METHODS: Assessments were scheduled at 20, 30, and 36 weeks' gestation and 2, 12, 26, and 52 weeks postpartum. Symptoms were assessed using the Structured Interview Guide for the Hamilton Depression Rating Scale-Atypical Depression Supplement (SIGH-ADS) and Mania Rating Scale (MRS). RESULTS: Pregnant women (N=152) with BD were evaluated; 88 women (58%) were treated and 64 untreated (42%) with psychotropic drugs during pregnancy. Among the 88 women treated, 23 (26%) discontinued their medication in the first trimester and the remaining 65 (74%) were exposed throughout pregnancy or in the second and third trimesters. More than two-thirds (73%) of the women who remained in the study took psychotropic agents postpartum. The mean scores on the SIGH-ADS were in the mild range of depressive symptoms in both the psychotropic-treated and untreated groups in both pregnancy and postpartum. The majority of women had no or few symptoms of mania. Of the pregnant women treated with psychotropic agents, 66% received a guideline-concordant drug, and 34% received either antidepressant monotherapy (for BD I) or mono- or polypharmacy with a variety of other agents. CONCLUSIONS: This sample of perinatal women with BD was characterized by mild residual symptoms of depression independent of pharmacotherapy, which poses a risk for recurrence and impaired parenting. The treatment of childbearing women with BD deserves urgent clinical and research attention to improve psychiatric outcomes.

Neonatal Discontinuation Syndrome in Serotonergic Antidepressant-Exposed Neonates.

OBJECTIVE: To determine whether infants exposed in utero to serotonin reuptake inhibitor (SRI) antidepressants or a DSM-IV-TR-defined mood disorder have significantly more neonatal discontinuation signs compared to an unexposed group of infants at 2-4 weeks after birth. METHODS: This secondary analysis was derived from 2 observational studies with enrollment from July 2000 to December 2011 in Cleveland, Ohio, and Pittsburgh, Pennsylvania. Mothers (n = 214) belonged to one of 3 groups based on exposure status during pregnancy: (1) Comparison-women who did not take psychotropics during pregnancy and had no major mood disorder; (2) SRI-exposed-women with a mood disorder who were taking an SRI but no benzodiazepines; and (3) Mood Disorder-women with depression or bipolar disorder who did not take psychotropic medications. The infants were examined for signs according to the Finnegan Scale by evaluators blind to maternal exposure status. RESULTS: The rates of sign presence (defined as a score ≥ 2 on the Finnegan Scale) in the SRI, Mood Disorder, and Comparison groups were similar at 34.1%, 35.1%, and 30.4%, respectively. Women in the SRI group had a significantly higher preterm birth rate (24.4%) compared to the other 2 groups (7.4% and 8.9% in the Mood Disorder and Comparison groups, respectively; P = .012). Preterm newborns had a significantly higher sign rate compared to full-term newborns (54% vs 31%, P = .020). We observed a significant relationship between Finnegan signs and preterm birth. CONCLUSIONS: The presence of neonatal signs at 2-4 weeks was more closely associated with prematurity than with in utero SRI or mood disorder exposure. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT00279370 and NCT00585702.

Transdermal Estradiol Treatment for Postpartum Depression: A Pilot, Randomized Trial.

Postpartum depression occurs in 14.5% of women in the first 3 months after birth. This study was an 8-week acute phase randomized trial with 3 cells (transdermal estradiol [E2], sertraline [SERT], and placebo [PL]) for the treatment of postpartum major depressive disorder. However, the study was stopped after batch analysis revealed that the E2 serum concentrations were lower than prestudy projections. This paper explores our experiences that will inform future investigations of therapeutic E2 use. Explanations for the low E2 concentrations were as follows: (1) study patch nonadhesion, which did not explain the low concentrations across the entire sample. (2) Ineffective transdermal patch preparations, although 2 different patch preparations were used and no significant main effect of patch type on E2 concentrations was found. (3) Obesity, at study entry, E2-treated women had body mass index of 32.9 (7.4) (mean [SD]). No pharmacokinetic data comparing E2 concentrations from transdermal patches in obese women versus normal weight controls are available. (4) Induction of cytochrome P450 (CYP450) 3A4 and other E2 elimination pathways in pregnancy. CYP4503A4 is induced in pregnancy and is a pathway for the metabolism of E2. Conversion to estrone and phase II metabolism via glucuronidation and sulfation, which also increase in pregnancy, are routes of E2 elimination. The time required for these pathways to normalize after delivery has not been elucidated. The observation that transdermal E2 doses greater than 100 µg/d did not increase serum concentrations was unexpected. Another hypothesis consistent with this observation is suppression of endogenous E2 secretion with increasing exogenous E2 dosing.

DOES SCREENING WITH THE MDQ AND EPDS IMPROVE IDENTIFICATION OF BIPOLAR DISORDER IN AN OBSTETRICAL SAMPLE?

BACKGROUND: Women with bipolar disorder (BD) are at high risk for postpartum affective episodes and psychosis. Although validated screening tools are available for postpartum unipolar depression, few screening tools for hypomania/mania exist. Screening tools for BD in the postpartum period are essential for improving detection and planning appropriate treatment. We evaluated whether adding the Mood Disorders Questionnaire (MDQ) to the Edinburgh Postnatal Depression Scale (EPDS) increased the identification of BD in the early postpartum period. METHODS: Women (N = 1,279) who delivered a live infant and screened positive on the EPDS and/or MDQ at 4-6 weeks postbirth were invited to undergo an in-home Structured Clinical Interview for DSM-IV (SCID). RESULTS: Positive EPDS and/or MDQ screens occurred in 12% of the sample (n = 155). In home SCID diagnostic interviews were completed in 93 (60%) of the mothers with positive screens. BD was the primary diagnosis in 37% (n = 34). Women with BD screened positive on the EPDS and/or MDQ as follows: EPDS+/MDQ+ (n = 14), EPDS+/MDQ- (n = 17), and EPDS-/MDQ+ (n = 3). The MDQ identified 50% (17/34) of the women with BD and 6 additional cases of BD when the MDQ question regarding how impaired the mother perceived herself was excluded from the screen criterion. CONCLUSION: Addition of the MDQ to the EPDS improved the distinction of unipolar depression from bipolar depression at the level of screening in 50% of women with traditional MDQ scoring and by nearly 70% when the MDQ was scored without the impairment criterion.

Theoretical approaches to maternal-infant interaction: which approach best discriminates between mothers with and without postpartum depression?

OBJECTIVE: The purpose of this study was to determine which of the four common approaches to coding maternal-infant interaction best discriminates between mothers with and without postpartum depression. METHODS: After extensive training, four research assistants coded 83 three minute videotapes of maternal infant interaction at 12month postpartum visits. Four theoretical approaches to coding (Maternal Behavior Q-Sort, the Dyadic Mini Code, Ainsworth Maternal Sensitivity Scale, and the Child-Caregiver Mutual Regulation Scale) were used. Twelve month data were chosen to allow the maximum possible exposure of the infant to maternal depression during the first postpartum year. The videotapes were created in a laboratory with standard procedures. Inter-rater reliabilities for each coding method ranged from .7 to .9. The coders were blind to depression status of the mother. RESULTS: Twenty-seven of the women had major depressive disorder during the 12month postpartum period. Receiver operating characteristics analysis indicated that none of the four methods of analyzing maternal infant interaction discriminated between mothers with and without major depressive disorder. CONCLUSION: Limitations of the study include the cross-sectional design and the low number of women with major depressive disorder. Further analysis should include data from videotapes at earlier postpartum time periods, and alternative coding approaches should be considered. Nurses should continue to examine culturally appropriate ways in which new mothers can be supported in how to best nurture their babies.

Impact of prenatal exposure to serotonin reuptake inhibitors or maternal major depressive disorder on infant developmental outcomes.

OBJECTIVE: To examine the impact of prenatal exposure to both serotonin reuptake inhibitors (SRIs; during any trimester) and maternal major depressive disorder (MDD; by DSM-IV criteria) on infant functioning. We hypothesized that infants with prenatal exposure to SRIs or MDD would have lower psychomotor, mental, and behavioral scores compared with nonexposed infants. METHOD: This longitudinal study included 166 mother-infant dyads: 68 with prenatal MDD/SRI (n = 41) or MDD/no SRI exposure (n = 27) and 98 nonexposed controls. Maternal depression and SRI exposure assessments were completed at or as near to 20, 30, and 36 prenatal weeks and 12, 26, 52, and 78 weeks postpartum as feasible. Infants were evaluated with the Bayley Scales of Infant Development, Second Edition, including the psychomotor (Psychomotor Development Index; PDI), cognitive (Mental Development Index; MDI), and behavioral (Behavioral Rating Scale; BRS) components. Study assessments occurred between 2003 and 2009. RESULTS: Neither prenatal exposure to MDD/SRI nor MDD/no SRI significantly impacted overall PDI, MDI, or BRS scores. However, we observed a significant SRI exposure by time interaction for the PDI (P = .038). MDD/SRI exposure was associated with lower PDI scores at 26 (mean = 97.0) and 52 weeks (mean = 92.9) compared with nonexposed infants (mean = 101.4 and 100.5). This difference was no longer significant at the 78-week assessment. CONCLUSIONS: Consistent with previous studies, we found no impact of prenatal MDD/SRI exposure on MDI scores. Less favorable PDI scores were observed in the first year; notably, these scores remained well within the normative range. The effects of prenatal MDD/SRI exposure on motor functioning may be transitory. A longitudinal pattern of poor developmental outcomes has not been established. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00279370.

Onset timing, thoughts of self-harm, and diagnoses in postpartum women with screen-positive depression findings.

IMPORTANCE: The period prevalence of depression among women is 21.9% during the first postpartum year; however, questions remain about the value of screening for depression. OBJECTIVES: To screen for depression in postpartum women and evaluate positive screen findings to determine the timing of episode onset, rate and intensity of self-harm ideation, and primary and secondary DSM-IV disorders to inform treatment and policy decisions. DESIGN: Sequential case series of women who recently gave birth. SETTING: Urban academic women's hospital. PARTICIPANTS: During the maternity hospitalization, women were offered screening at 4 to 6 weeks post partum by telephone. Screen-positive women were invited to undergo psychiatric evaluations in their homes. MAIN OUTCOMES AND MEASURES: A positive screen finding was an Edinburgh Postnatal Depression Scale (EPDS) score of 10 or higher. Self-harm ideation was assessed on EPDS item 10: "The thought of harming myself has occurred to me" (yes, quite often; sometimes; hardly ever; never). Screen-positive women underwent evaluation with the Structured Clinical Interview for DSM-IV for Axis I primary and secondary diagnoses. RESULTS: Ten thousand mothers underwent screening, with positive findings in 1396 (14.0%); of these, 826 (59.2%) completed the home visits and 147 (10.5%) completed a telephone diagnostic interview. Screen-positive women were more likely to be younger, African American, publicly insured, single, and less well educated. More episodes began post partum (40.1%), followed by during pregnancy (33.4%) and before pregnancy (26.5%). In this population, 19.3% had self-harm ideation. All mothers with the highest intensity of self-harm ideation were identified with the EPDS score of 10 or higher. The most common primary diagnoses were unipolar depressive disorders (68.5%), and almost two-thirds had comorbid anxiety disorders. A striking 22.6% had bipolar disorders. CONCLUSIONS AND RELEVANCE: The most common diagnosis in screen-positive women was major depressive disorder with comorbid generalized anxiety disorder. Strategies to differentiate women with bipolar from unipolar disorders are needed. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00282776.

Best practices: an emerging best practice model for perinatal depression care.

Perinatal depression is a significant health problem, especially among inner-city women. The authors explored the feasibility of an innovative model that integrated depression screening and treatment within an agency for maternal-child health. The team conducted depression screening with the Edinburgh Postnatal Depression Scale; they confirmed the primary diagnosis with the PRIME-MD instrument for 29 women with positive screens. Most participants had moderate or severe major depressive disorder. Women contended with multiple treatment barriers. Colocated depression care was highly acceptable and enabled evidence-based care delivery for at-risk mothers.

Identification of postpartum depression.

Postpartum depression (PPD) is the most common medical complication of childbearing. Universal screening maximizes the likelihood of prompt identification of PPD. Obstetrician-gynecologists routinely evaluate postpartum women for a general health examination and review of family planning options at approximately 6 weeks after birth; therefore, they are well positioned to identify PPD. In this study, we review the diagnostic criteria for postpartum depressive disorders and clinical risk factors predictive of PPD. We examine depression screening tools, appropriate cut-points associated with positive screens, the optimal timing for screening, and the acceptability of depression screening in obstetrical settings. Finally, we explore how to manage patients who screen positive for depression and treatment options for women with PPD.

Transdermal estradiol for postpartum depression: a promising treatment option.

Postpartum depression (PPD) is the most common unrecognized complication of childbirth and affects 1 out of 7 childbearing women. Although conventional pharmacologic and psychotherapeutic antidepressant treatments are effective for PPD, a natural alternative may be preferred by postpartum women, especially those who breastfeed their infants. The treatment of PPD with synthetic forms of naturally occurring estrogen is mechanistically appealing because PPD occurs in the context of estrogen withdrawal at parturition. Preliminary evidence suggests that PPD is a disorder of hormone-related mood dysregulation (similar to perimenopausal depression) that can be effectively treated with estrogen. This review provides the basic science and clinical background as well as safety considerations to support the application of transdermal estradiol as a treatment for PPD. We conclude that estradiol treatment for PPD requires confirmation of efficacy in a randomized clinical trial before routine clinical use as monotherapy. Additional data regarding maternal tolerability of cyclic progestins, long-term safety of estradiol treatment, estradiol passage into breast milk and infants, and interdisciplinary collaboration among psychiatrists and gynecologists is also needed before estradiol is used in women who decline or fail to respond to first-line antidepressant treatments, or as an augmentation of conventional antidepressant treatment.

Prepregnancy body mass index, gestational weight gain, and the likelihood of major depressive disorder during pregnancy.

OBJECTIVE: We assessed the relation between prepregnancy body mass index (BMI) and the likelihood of major depressive disorder (MDD) during pregnancy and tested whether this association was modified by gestational weight gain. METHOD: Women (N = 242) were enrolled at < 20 weeks gestation into a prospective cohort study. Diagnosis of MDD was made with the Structured Clinical Interview for DSM-IV at 20, 30, and 36 weeks gestation. Gestational weight gain was compared with the 1990 Institute of Medicine weight gain recommendations. To assess the independent association between prepregnancy BMI and the odds of MDD, MDD at each time point was used as the dependent measure in a multivariable longitudinal logistic regression model employing generalized estimating equations. The data were collected from 2003-2007. RESULTS: There was a strong, positive dose-response association between prepregnancy BMI and the likelihood of MDD (P = .002). Compared with a BMI of 18, the adjusted odds ratios (95% confidence interval) for BMIs of 23, 28, and 33 were 1.4 (1.1 to 1.7), 1.9 (1.3 to 2.9), and 2.6 (1.4 to 4.3), respectively. Gestational weight gain significantly modified this effect. Among women with weight gains within and above the 1990 Institute of Medicine recommendations, pregravid overweight was associated with a greater likelihood of MDD. In contrast, all women with weight gains below recommended levels had an elevated odds of depression regardless of their pregravid BMI (P < .05). CONCLUSIONS: Because pregravid overweight, poor gestational weight gain, and MDD all pose substantial risks for fetal development and birth outcomes, health care providers should monitor depression levels in these women to facilitate appropriate depression intervention.

Major depression and antidepressant treatment: impact on pregnancy and neonatal outcomes.

OBJECTIVE: Selective serotonin reuptake inhibitor (SSRI) use during pregnancy incurs a low absolute risk for major malformations; however, other adverse outcomes have been reported. Major depression also affects reproductive outcomes. This study examined whether 1) minor physical anomalies, 2) maternal weight gain and infant birth weight, 3) preterm birth, and 4) neonatal adaptation are affected by SSRI or depression exposure. METHOD: This prospective observational investigation included maternal assessments at 20, 30, and 36 weeks of gestation. Neonatal outcomes were obtained by blinded review of delivery records and infant examinations. Pregnant women (N=238) were categorized into three mutually exclusive exposure groups: 1) no SSRI, no depression (N=131); 2) SSRI exposure (N=71), either continuous (N=48) or partial (N=23); and 3) major depressive disorder (N=36), either continuous (N=14) or partial (N=22). The mean depressive symptom level of the group with continuous depression and no SSRI exposure was significantly greater than for all other groups, demonstrating the expected treatment effect of SSRIs. Main outcomes were minor physical anomalies, maternal weight gain, infant birth weight, pregnancy duration, and neonatal characteristics. RESULTS: Infants exposed to either SSRIs or depression continuously across gestation were more likely to be born preterm than infants with partial or no exposure. Neither SSRI nor depression exposure increased risk for minor physical anomalies or reduced maternal weight gain. Mean infant birth weights were equivalent. Other neonatal outcomes were similar, except 5-minute Apgar scores. CONCLUSIONS: For depressed pregnant women, both continuous SSRI exposure and continuous untreated depression were associated with preterm birth rates exceeding 20%.

Postpartum depression: a randomized trial of sertraline versus nortriptyline.

Symptom reduction and improvement in functioning in women with postpartum major depression treated with a tricyclic antidepressant versus a serotonin reuptake inhibitor were compared. The design was a double-blind, 8-week comparative trial of nortriptyline (NTP) versus sertraline (SERT) with a 16-week continuation phase. Women aged 18 to 45 years with postpartum major depression and a 17-item Hamilton Rating Scale for Depression score of 18 or more were eligible. Subjects were randomized to NTP or SERT and treated with a fixed-dosing strategy. Of 420 women interviewed, 109 eligible women received medication, and 95 provided follow-up data. The proportion of women who responded and remitted did not differ between drugs at 4, 8, or 24 weeks. Times to response and remission also did not differ. Psychosocial functioning improved similarly in both drug-treated groups of mothers. The total side effect burden of each drug was similar, although side effect profiles differed between agents. No clinical or demographic variables differentiated responders by drug. Women who were responders and remitters at week 8 could be identified earlier if they were treated with SERT than with NTP. Breast-fed infant serum levels were near or below the level of quantifiability for both agents.