Dorothy Sit

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.

Abstract: 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.

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.

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.

Postpartum depression: a disorder in search of a definition

The Diagnostic and Statistical Manual (DSM-IV) has the following goal: “to provide clear descriptions of diagnostic categories in order to enable clinicians and investigators to diagnose, communicate about, study, and treat people with various mental disorders.” The DSM-IV also includes specifiers for mood disorders that are intended to increase diagnostic specificity and create homogeneous subgroups, drive treatment selection, and improve the prediction of prognosis. With postpartum onset is a specifier with two requirements: 1) a time criterion (onset of episode within 4 weeks after birth), and 2) application to the current or most recent episode of four diagnoses (major depressive disorder; major depressive, manic, or mixed episode in bipolar I or II disorder; or brief psychotic disorder). However, the term postpartum depression has been used to describe a broad variety of childbearing-related mood episodes not included in the DSM-IV definition. Gaynes et al. (2005) used an expanded concept of perinatal depression (during pregnancy through one year postpartum) in their report (commissioned by the Agency for Healthcare Research and Quality) to inform national policy. From a public health perspective, women, families and communities suffer regardless of when the maternal episode begins. The purpose of this paper is to examine the DSM-IV definition of with postpartum onset and challenges in its clinical and research application. Our goal is to frame the discussion about the specifier as revisions of the DSM and International Classification of Diseases (ICD) codes are considered. We focus on major depressive disorder (MDD) to highlight the ways in which the definition of the postpartum onset specifier might be modified.

The Effect of Gastric Bypass on the Pharmacokinetics of Serotonin Reuptake Inhibitors

OBJECTIVE Morbidly obese patients frequently present with mood and anxiety disorders, which are often treated with serotonin reuptake inhibitors (SRIs). Having observed that patients treated with SRIs frequently relapse after Roux-en-Y gastric bypass surgery, the authors sought to assess whether SRI bioavailability is reduced postoperatively. METHOD Twelve gastric bypass candidates treated with an SRI for primary mood or anxiety disorders were studied prospectively. Timed blood samples for SRI plasma levels were drawn for pharmacokinetic studies before surgery and 1, 6, and 12 months afterward. Maximum concentration, time to maximum concentration, and area under the concentration/time curve (AUC) were determined. RESULTS In eight of the 12 patients, AUC values 1 month after surgery dropped to an average of 54% (SD=18) of preoperative levels (range=36%-80%); in six of these patients, AUC values returned to baseline levels (or greater) by 6 months. Four patients had an exacerbation of depressive symptoms, which resolved by 12 months in three of them. Three of the four patients had a reduced AUC level at 1 month and either gained weight or failed to lose weight between 6 and 12 months. Normalization of the AUC was associated with improvement in symptom scores. CONCLUSIONS Patients taking SRIs in this study were at risk for reduced drug bioavailability 1 month after Roux-en-Y gastric bypass. The authors recommend close psychiatric monitoring after surgery.

Does Fetal Exposure to SSRIs or Maternal Depression Impact Infant Growth

OBJECTIVE The aim of this study was to compare the growth of infants born to women with antenatal major depressive disorder, either untreated or treated with selective serotonin reuptake inhibitor (SSRI) antidepressants, and infants born to a nondepressed, nonmedicated comparison group across the first year of life. METHOD In this prospective observational study, pregnant women were evaluated at weeks 20, 30, and 36 of gestation, and mother and infant pairs were assessed at 2, 12, 26, and 52 weeks postpartum. Three nonoverlapping groups of women were defined according to their pregnancy exposures: 1) no SSRI and no depression (N=97), 2) SSRI (N=46), and 3) major depression without SSRI (N=31). Maternal demographic and clinical characteristics and newborn outcomes were compared across exposure groups. Infant weight, length, and head circumference were measured by a physician or physicians assistant who was blind to depression and SSRI exposure status at each postpartum time point. RESULTS Both adjusted and unadjusted analyses revealed neither antenatal major depression nor SSRI exposure was significantly associated with infant weight, length, or head circumference relative to nonexposure to either. In addition, the interaction of group and prepregnancy body mass index was also evaluated, and no significant synergistic effect was identified. Similarly, no differential effect of group over time was observed for weight, length, or head circumference. CONCLUSIONS In utero exposure to major depression or SSRI antidepressants did not affect infant growth with respect to weight, length, or head circumference from birth through 12 months of age.

Depression treatment and maternal functioning.

Background: In women with major depressive disorder (MDD), maternal role functioning is negatively impacted but has been shown to improve with treatment; however, most investigations have not included a control group or studied women longitudinally. We hypothesized that women with MDD who responded to serotonin selective reuptake inhibitors (SSRIs) would have overall functioning and maternal role functioning scores similar to that of the control group and superior to women with MDD (either untreated or nonresponsive to SSRIs). Methods: This prospective, longitudinal observational study (n = 215) included postpartum assessments at 2 1/2 weeks, 3 months, 6 months, and 12 months. Postpartum women were categorized into four mutually exclusive exposure groups by depression and medication status: (1) Control group (no SSRI, no MDD; (2) Responder (SSRI, no MDD); (3) Untreated (MDD, no SSRI); and (4) Nonresponder (Both MDD and SSRI). Outcome variables include a measure of overall functioning (Global Assessment Scale, GAS) and three measures of maternal role functioning (Maternal Self Efficacy, ICS; Gratification in Maternal Role, GRAT; and overall maternal role functioning, IFSAC). Results: The study hypothesis was supported. Responders had scores related to overall functioning and maternal role functioning that were similar to the control group and superior to nonresponders and untreated women with MDD, as measured by the GAS and the GRAT. Conclusion: Postpartum depression treatment optimally targets both symptom improvement and maternal functional recovery. The GRAT is a simple, self‐administered instrument that can be used with a depression measure to assess maternal role functioning. Depression and Anxiety, 2011.

Disturbed sleep, a novel risk factor for preterm birth?

OBJECTIVE The etiology of preterm birth (PTB) is likely caused by multiple factors, which may include disturbed sleep. We evaluated whether sleep disturbance was associated with PTB and whether the association was affected by other psychosocial risk factors. METHODS Pregnant women (n=217) for whom we had depression and sleep data at 20 or 30 weeks gestation and delivery information were evaluated. Logistic models were used to test the hypotheses that disturbed sleep was associated with PTB. RESULTS Time in bed at 20 weeks was significantly associated with risk for preterm delivery (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.08-1.88). However, after controlling for depression/selective serotonin reuptake inhibitors (SSRI) status, history of PTB, age, employment, and marital status, this relationship was no longer significant (OR 1.26, 95% CI .92-1.71). No other relationships were significant. CONCLUSIONS We report preliminary evidence suggesting that poor sleep may contribute to risk for PTB. Although it is speculative and additional work is needed to confirm or refute whether sleep is an independent or mediating risk factor for PTB, disturbed sleep does appear to play a role in adverse pregnancy outcomes.