Progression of depression and anxiety symptoms in pregnancies conceived by assisted reproductive technology in the United States.

PURPOSE: Women who utilize assisted-reproductive technology (ART) to achieve pregnancy experience unique circumstances before and during their pregnancy. This study aims to examine the progression of mental health in pregnant women who conceived via various methods of ART to understand gestational time periods of emotional stability or risk specific to these populations. METHODS: Secondary analysis of the Yale Pink and Blue Study - a prospective cohort involving women from 137 obstetrical practices in the northeastern United States between 2005-2009. Depressive and anxiety symptoms among spontaneous, planned pregnancies were compared to ART pregnancies using the Edinburgh Postnatal Depression Scale (EPDS) and its anxiety subscale (EPDS-3A), respectively. Generalized Estimating Equations were used to compare group changes (EPDS and EPDS-3A score threshold ≥10) at timepoints of <17 weeks (T1), 28(±2) weeks (T2), and 8(±4) weeks postpartum (T3). RESULTS: 1,466 spontaneous, planned pregnancies were compared to 191 pregnancies conceived via ART. Prevalence of depressive symptoms were similar between conception groups. Change in prevalence over time differed significantly between those groups (from T1 to T3 (ß 0.59), as well as between spontaneous pregnancies compared to autologous gamete ART pregnancies (from T1 to T2 (ß 0.48) and T1 to T3 (ß 0.65). Course of anxiety did not differ between conception groups. CONCLUSIONS: Women who conceive via ART have different rates of change in depressive symptoms throughout gestation compared to women with spontaneous pregnancies.

Premenstrual disorders.

Premenstrual disorders include premenstrual syndrome, premenstrual dysphoric disorder, and premenstrual worsening of another medical condition. While the underlying causes of these conditions continue to be explored, an aberrant response to hormonal fluctuations that occurs with the natural menstrual cycle and serotonin deficits have both been implicated. A careful medical history and daily symptom monitoring across 2 menstrual cycles is important in establishing a diagnosis. Many treatments have been evaluated for the management of premenstrual disorders. The most efficacious treatments for premenstrual syndrome and premenstrual dysphoric disorder include serotonin reuptake inhibitors and contraceptives with shortened to no hormone-free interval. Women who do not respond to these and other interventions may benefit from gonadotropin-releasing hormone agonist treatment.

Association of Panic Disorder, Generalized Anxiety Disorder, and Benzodiazepine Treatment During Pregnancy With Risk of Adverse Birth Outcomes.

Importance: Registry data show that maternal panic disorder, or anxiety disorders in general, increase the risk for adverse pregnancy outcomes. However, diagnoses from registries may be imprecise and may not consider potential confounding factors, such as treatment with medication and maternal substance use. Objective: To determine whether panic disorder or generalized anxiety disorder (GAD) in pregnancy, or medications used to treat these conditions, are associated with adverse maternal or neonatal pregnancy outcomes. Design, Setting, and Participants: This cohort study conducted between July 1, 2005, and July 14, 2009, recruited women at 137 obstetric practices in Connecticut and Massachusetts before 17 weeks of pregnancy and reassessed them at 28 (±4) weeks of pregnancy and 8 (±4) weeks postpartum. Psychiatric diagnoses were determined by answers to the World Mental Health Composite International Diagnostic Interview. Assessments also gathered information on treatment with medications and confounding factors, such as substance use, previous adverse birth outcomes, and demographic factors. Exposure: Panic disorder, GAD, or use of benzodiazepines or serotonin reuptake inhibitors. Main Outcomes and Measures: Among mothers: preterm birth, cesarean delivery, and hypertensive diseases of pregnancy. Among neonates: low birth weight, use of minor respiratory interventions, and use of ventilatory support. Results: Of the 2654 women in the final analysis (mean [SD] age, 31.0 [5.7] years), most were non-Hispanic white (1957 [73.7%]), 98 had panic disorder, 252 had GAD, 67 were treated with a benzodiazepine, and 293 were treated with a serotonin reuptake inhibitor during pregnancy. In adjusted models, neither panic disorder nor GAD was associated with maternal or neonatal complications of interest. Most medication exposures occurred early in pregnancy. Maternal benzodiazepine use was associated with cesarean delivery (odds ratio [OR], 2.45; 95% CI, 1.36-4.40), low birth weight (OR, 3.41; 95% CI, 1.61-7.26), and use of ventilatory support for the newborn (OR, 2.85; 95% CI, 1.2-6.9). Maternal serotonin reuptake inhibitor use was associated with hypertensive diseases of pregnancy (OR, 2.82; 95% CI, 1.58-5.04), preterm birth (OR, 1.56; 95% CI, 1.02-2.38), and use of minor respiratory interventions (OR, 1.81; 95% CI, 1.39-2.37). With maternal benzodiazepine treatment, rates of ventilatory support increased by 61 of 1000 neonates and duration of gestation was shortened by 3.6 days; with maternal serotonin reuptake inhibitor use, gestation was shortened by 1.8 days, 152 of 1000 additional newborns required minor respiratory interventions, and 53 of 1000 additional women experienced hypertensive diseases of pregnancy. Conclusions and Relevance: Panic disorder and GAD do not contribute to adverse pregnancy complications. Women may require treatment with medications during pregnancy, which can shorten the duration of gestation slightly. Maternal treatment with a serotonin reuptake inhibitor is also associated with hypertensive disease of pregnancy and cesarean delivery.

Progesterone Reduces Cocaine Use in Postpartum Women with a Cocaine Use Disorder: A Randomized,Double-Blind Study.

BACKGROUND: Progesterone modulates multiple brain functions implicated in the pathogenesis ofdrug addiction. During high endogenous progesterone states, women reduce use of cocaine. We sought to test whether progesterone replacement reduces cocaine use in postpartum women with a cocaine use disorder (CUD). METHODS: A 12-week, double-blind, parallel, randomized, placebo-controlled pilot trial with a 3-month post trial follow-up. 25 women within 12 weeks of deliverywere randomized to placeboand 25 to100 mgs of oral micronized progesterone, administered twice daily. Participants were recruited from obstetrical clinics. Randomization and allocation were performed by the study biostatistician. Attrition was 18% and the analysis included all50participants. Outcomes were self-reported days of cocaine use and positive urine toxicology assays for cocaine metabolites. FINDINGS: Participants randomized to placebo compared to progesterone had increased likelihood of cocaine use per week (RR=1·19; 95% confidence interval (CI)=1·05 to 1·36; p<0·01). At the three-month post trial visit the difference between groups was not significant (Likelihood RatioΧ2 =5·16; P=·08). There were no group differences in rates of submission of a positive urine test. A post hoc analysis showed a higher rate of relapse for participants randomized to placebo (HR=4·71; 95% CI= 1·09 to 20·5). We did not observe groups differences in the rate of adverse events. INTERPRETATION: These preliminary findings support the promise of progesterone treatment in postpartum women with a CUD and could constitute a therapeutic break through. FUNDING: US National Institute on Drug Abuse; Veterans Administration.

Pregnant women with posttraumatic stress disorder and risk of preterm birth.

IMPORTANCE: Posttraumatic stress disorder (PTSD) occurs in about 8% of pregnant women. Stressful conditions, including PTSD, are inconsistently linked to preterm birth. Psychotropic treatment has been frequently associated with preterm birth. Identifying whether the psychiatric illness or its treatment is independently associated with preterm birth may help clinicians and patients when making management decisions. OBJECTIVE: To determine whether a likely diagnosis of PTSD or antidepressant and benzodiazepine treatment during pregnancy is associated with risk of preterm birth. We hypothesized that pregnant women who likely had PTSD and women receiving antidepressant or anxiolytic treatment would be more likely to experience preterm birth. DESIGN, SETTING, AND PARTICIPANTS: Longitudinal, prospective cohort study of 2654 women who were recruited before 17 completed weeks of pregnancy from 137 obstetrical practices in Connecticut and Western Massachusetts. EXPOSURES: Posttraumatic stress disorder, major depressive episode, and use of antidepressant and benzodiazepine medications. MAIN OUTCOMES AND MEASURES: Preterm birth, operationalized as delivery prior to 37 completed weeks of pregnancy. Likely psychiatric diagnoses were generated through administration of the Composite International Diagnostic Interview and the Modified PTSD Symptom Scale. Data on medication use were gathered at each participant interview. RESULTS: Recursive partitioning analysis showed elevated rates of preterm birth among women with PTSD. A further split of the PTSD node showed high rates for women who met criteria for a major depressive episode, which suggests an interaction between these 2 exposures. Logistic regression analysis confirmed risk for women who likely had both conditions (odds ratio [OR], 4.08 [95% CI, 1.27-13.15]). For each point increase on the Modified PTSD Symptom Scale (range, 0-110), the risk of preterm birth increased by 1% to 2%. The odds of preterm birth are high for women who used a serotonin reuptake inhibitor (OR, 1.55 [95% CI, 1.02-2.36]) and women who used a benzodiazepine medication (OR, 1.99 [95% CI, 0.98-4.03]). CONCLUSIONS AND RELEVANCE: Women with likely diagnoses of both PTSD and a major depressive episode are at a 4-fold increased risk of preterm birth; this risk is greater than, and independent of, antidepressant and benzodiazepine use and is not simply a function of mood or anxiety symptoms.

Pregnancy-specific stress, preterm birth, and gestational age among high-risk young women.

OBJECTIVE: There is evidence that pregnancy-specific stress is associated with preterm birth. The purpose of this study is to examine the association between change in pregnancy-specific stress over the course of pregnancy and birth outcomes (i.e., preterm birth and gestational age) in an understudied but vulnerable group using a theoretically derived model. METHODS: Multivariate linear and logistic regression techniques were used to examine the association between pregnancy-specific stress (measured in second and third trimester) and length of gestation (i.e., preterm birth and gestational age) among a sample of 920 Black and/or Latina adolescent and young women. RESULTS: Second trimester pregnancy-specific stress was not associated with preterm birth or gestational age. Third trimester pregnancy-specific stress was associated with preterm birth but not with gestational age. Change in pregnancy-specific stress between second and third trimester was significantly associated with increased likelihood of preterm delivery and shortened gestational age, even after controlling for important biological, behavioral, psychological, interpersonal, and sociocultural risk factors. CONCLUSIONS: Findings emphasize the importance of measuring pregnancy-specific stress across pregnancy, as the longitudinal change from second to third trimester was significantly associated with length of gestation measured both as a dichotomous variable (preterm birth) and a continuous variable (gestational age). Furthermore, this is the first study to observe the association of pregnancy-specific stress with length of gestation in this understudied population-unique in age, race, and ethnicity.

A pilot study to compare fluoxetine, calcium, and placebo in the treatment of premenstrual syndrome.

Serotonin reuptake inhibitors and calcium supplements ameliorate symptoms of premenstrual syndrome. A comparison of these agents to placebo may guide treatment selection. The goal of this pilot study was to compare fluoxetine and calcium to placebo.We enrolled 39 women with at least 3 moderate to severe premenstrual symptoms and functional impairment. The trial compared fluoxetine (10 mg twice daily), calcium carbonate (600 mg twice daily), and placebo over the course of 4 menstrual cycles. The Inventory of Depressive Symptomatology, Premenstrual Tension Scale, Clinical Global Impression-Severity and -Improvement scales, and Daily Record of Severity of Problems were used to measure symptoms.Symptom improvement was greatest for the fluoxetine group, although significance was achieved only for the Daily Record of Severity of Problems (ß = -0.28; 95% confidence interval, -1.70 to -0.35; P = 0.02) and the Clinical Global Impression-Improvement (ß = -1.03; 95% confidence interval= -1.70 to -0.35; P = 0.04). The Cohen d effect sizes for fluoxetine relative to placebo were between 0.80 and 2.08, whereas the effect sizes for calcium were only between 0.10 and 0.44.Fluoxetine had clear therapeutic benefit for premenstrual syndrome, whereas the effect of calcium was much smaller. Results of this pilot do not support the need for a larger study that would compare these compounds.

Diagnosis, pathophysiology, and management of mood disorders in pregnant and postpartum women.

Mood disorders disproportionately affect women across the lifespan. Mood disorders in pregnancy and the postpartum period are common and have profound implications for women and their children. These include obstetric and neonatal complications, impaired mother-infant interactions, and, at the extreme, maternal suicide and infanticide. Because obstetrician-gynecologists are often the first (and sometimes the only) point of contact for young women in the health care system, familiarity with the presentation and treatment of depressive illness in the perinatal period is imperative. The goal of this review is to synthesize essential information on depressive illness in the perinatal period with a focus on its most common and severe presentations, major depressive disorder and bipolar disorder. Accurate diagnosis of unipolar major depressive disorder from bipolar disorder can facilitate the selection of the best possible treatment alternatives. Counseling may be sufficient for perinatal women who have mild to moderate depression, but women who are severely depressed are likely to require antidepressant treatment. Women with bipolar disorder are at high risk for relapse if mood stabilizer medication is discontinued, and they are vulnerable to relapse near the time of delivery. Comanagement of their care with psychiatrists will increase their chances of avoiding a recurrence of illness.

Generalized anxiety disorder: course and risk factors in pregnancy.

BACKGROUND: There are limited studies of generalized anxiety disorder (GAD) across pregnancy. METHODS: Women (n = 2793) were enrolled in the Yale Pink and Blue study, a cohort enriched with subjects who suffered from major depressive disorder (MDD) within the past five years or used antidepressants in the past year. Subjects were evaluated with the Composite International Diagnostic Interview at three time points: twice in pregnancy and once after delivery. We defined a generalized anxiety disorder (GAD) episode as per DSM IV but with required duration reduced to one month or longer. Course and correlates of GAD were examined in women who had: 1) no GAD during the 6 months prior or in pregnancy (Group A), 2) GAD in the 6 months prior to but not in pregnancy (Group B), 3) GAD in pregnancy only (Group C) and 4) GAD both in the 6 months prior to and during pregnancy (Group D). RESULTS: 9.5% of the cohort suffered from GAD at some point in pregnancy. Anxiety symptoms were highest in the first trimester and decreased across pregnancy. Regression analysis revealed that previous GAD episodes, education, social support and a history of child abuse distinguished between membership in the four groups. LIMITATIONS: The sample may not be representational, as it was enhanced with those at risk, and had relatively low representation of socio-economically disadvantaged women. CONCLUSIONS: Identification of anxious patients during pregnancy may provide an opportunity to engage those in need of psychiatric treatment.

Typical somatic symptoms of pregnancy and their impact on a diagnosis of major depressive disorder.

OBJECTIVE: We sought to determine whether trimester of pregnancy influences the ability to diagnose major depressive disorder (MDD). METHOD: Eight hundred thirty-eight subjects completed a Composite International Diagnostic Interview and the Edinburgh Postnatal Depression Scale (EPDS) before 17 weeks of pregnancy, at 26-30 weeks of pregnancy and at 4-12 weeks postpartum. Subjects responded to a checklist of MDD symptoms regardless of stem question endorsement. We compared rates of symptom expression by response (Y/N) to stem questions, and trimester, using logit analysis. Receiver operating characteristic curves determined optimal EPDS thresholds. RESULTS: Most symptoms from the DSM-IV checklist were endorsed significantly more often in the first compared to later trimesters (odds ratios ranged from 1.39 to 14.16 for the first vs. later trimesters), independent of response to depression stem questions or medication treatment. Despite this, stem-positive and stem-negative groups differed significantly for 10 out of 13 symptoms (odds ratios, 2.29-6.89), independent of trimester. The EPDS had an optimal cutoff of 10 and showed acceptable predictive value. CONCLUSIONS: Pregnant women commonly experience somatic and other symptoms in this first trimester, but depressed women still differ from those who are not depressed. "Appetite increase," "oversleeping" and "increase in energy" (e.g., agitation) were uninformative with regard to an MDD diagnosis.

A treatment for substance abusing pregnant women.

We describe the adaptation of a manualized behavioral treatment for substance using pregnant women that includes components of motivational interviewing and cognitive therapy. In a pilot study conducted in 2006-2007, five non-behavioral health clinicians were trained to provide the treatment to 14 women. Therapy was administered concurrent with routine prenatal care at inner-city maternal health clinics in New Haven and Bridgeport, Connecticut, small urban cities in the USA. Substance use was monitored by self report, and urine and breath tests. Treatment fidelity was assessed using the Yale Adherence and Competence System. Behavioral treatment delivery in this setting is feasible and is being evaluated in a randomized, controlled, clinical trial.

Update on research and treatment of premenstrual dysphoric disorder.

Many women in their reproductive years experience some mood, behavioral. or physical symptoms in the week prior to menses. Variability exists in the level of symptom burden in that some women experience mild symptoms, whereas a small minority experience severe and debilitating symptoms. For an estimated 5%-8% of premenopausal women, work or social functioning are affected by severe premenstrual syndrome. Many women in this group meet diagnostic criteria for premenstrual dysphoric disorder (PMDD). Among women who suffer from PMDD, mood and behavioral symptoms such as irritability, depressed mood, tension, and labile mood dominate. Somatic complaints, including breast tenderness and bloating, also can prove disruptive to women's overall functioning and quality of life. Recent evidence suggests that individual sensitivity to cyclical variations in levels of gonadal hormones may predispose certain women to experience these mood, behavioral, and somatic symptoms. Treatments include: antidepressants of the serotonin reuptake inhibitor class, taken intermittently or throughout the menstrual cycle; medications that suppress ovarian cyclicity; and newer oral contraceptives with novel progestins.

Premenstrual syndrome.

Most women of reproductive age have some physical discomfort or dysphoria in the weeks before menstruation. Symptoms are often mild, but can be severe enough to substantially affect daily activities. About 5-8% of women thus suffer from severe premenstrual syndrome (PMS); most of these women also meet criteria for premenstrual dysphoric disorder (PMDD). Mood and behavioural symptoms, including irritability, tension, depressed mood, tearfulness, and mood swings, are the most distressing, but somatic complaints, such as breast tenderness and bloating, can also be problematic. We outline theories for the underlying causes of severe PMS, and describe two main methods of treating it: one targeting the hypothalamus-pituitary-ovary axis, and the other targeting brain serotonergic synapses. Fluctuations in gonadal hormone levels trigger the symptoms, and thus interventions that abolish ovarian cyclicity, including long-acting analogues of gonadotropin-releasing hormone (GnRH) or oestradiol (administered as patches or implants), effectively reduce the symptoms, as can some oral contraceptives. The effectiveness of serotonin reuptake inhibitors, taken throughout the cycle or during luteal phases only, is also well established.

A descriptive analysis of minor depression.

OBJECTIVE: The authors provide a detailed clinical description of minor depression: its symptoms, level of disability, stability, and relationship to patient and family history of major depressive disorder. METHOD: Rigorous criteria for minor depression, including functional disability, were used to identify 226 individuals for a three-phase treatment study. This report presents data obtained on that study group during the first study phase, a 4-week placebo lead-in period. RESULTS: One hundred sixty-two subjects (72% of the initial study group) remained in the study for 4 weeks and continued to meet criteria for minor depression. Minor depression in these subjects was primarily characterized by mood and cognitive symptoms, not the classical neurovegetative signs and symptoms of depression. Approximately one-third of the subjects with minor depression had a past history of major depressive disorder, and nearly half had a family history of unipolar depressive disorder; however, neither factor affected the severity or quality of minor depressive symptoms. CONCLUSIONS: These data suggest that 1) minor depression is not evanescent; 2) minor depression is characterized by mood and cognitive symptoms rather than neurovegetative symptoms; 3) minor depression may occur either independently of a lifetime history of major depressive disorder or as a stage of illness in the course of recurrent unipolar depressive disorder; and 4) depressive disorders should be conceptualized as a continuum of severity.