Stressors and coping mechanisms among pregnant women with psychiatric disorders during the COVID-19 pandemic.

BACKGROUND: Women with psychiatric disorders are vulnerable to relapse in pregnancy, and the COVID-19 pandemic has presented an additional stressor. METHODS: Data came from a supplemental study offered to women enrolled in the Massachusetts General Hospital Center for Women's Mental Health National Pregnancy Registry for Psychiatric Medications. Registry participants were also invited to complete an email questionnaire relating to their experiences of pregnancy during the pandemic. Prepartum experiences of 230 respondents were analyzed. RESULTS: The most common diagnoses in this group were depression (30%), anxiety disorders (29%), and bipolar affective disorder (17%). Common stressors included changes in employment, greater childcare and/or schooling responsibilities, more conflict in the household, and increased isolation. Participants reported negative impacts and/or coping mechanisms associated with the pandemic, such as sleep problems, reduced physical activity, changes in eating, and greater amounts of screen time. Positive impacts and/or coping mechanisms were also reported, including more quality time with family, more time in nature, and being more appreciative of aspects of life previously taken for granted. CONCLUSIONS: Our findings suggest that the COVID-19 pandemic has had an overall negative psychosocial impact on many pregnant women with preexisting psychiatric disorders. We also observed positive coping mechanisms, which could be drawn on as sources of resilience.

Client and Provider Experiences in Uganda Suggest Demand for and Highlight the Importance of Addressing HIV Stigma and Gender Norms Within Safer Conception Care.

Safer conception counseling supports HIV-serodifferent couples to meet reproductive goals while minimizing HIV transmission risk, but has not been integrated into routine HIV care. We piloted a novel safer conception program in an established public-sector HIV clinic in Uganda to inform future implementation. In-depth interviews and counseling observations explored experiences of program clients and healthcare providers to assess program acceptability, appropriateness, and feasibility. Fifteen index clients (8 women, 7 men), 10 pregnancy partners, and 10 providers completed interviews; 15 participants were living with HIV. Ten observations were conducted. We identified four emergent themes: (1) High demand for safer conception services integrated within routine HIV care, (2) Evolving messages of antiretroviral treatment as prevention contribute to confusion about HIV prevention options, (3) Gender and sexual relationship power inequities shape safer conception care, and (4) HIV-related stigma impacts safer conception care uptake. These findings confirm the need for safer conception care and suggest important implementation considerations.

Body Mass Index as a Moderator of Treatment Response to Ketamine for Major Depressive Disorder.

PURPOSE/BACKGROUND: Major depressive disorder (MDD) and obesity commonly co-occur. We sought to assess the impact of body mass index (BMI) on the acute antidepressant effects of ketamine in patients with treatment-resistant depression. METHODS/PROCEDURES: Post hoc analyses were conducted from a multisite, randomized, double-blind, placebo-controlled trial designed to assess the rapid-onset effects of intravenous ketamine. Patients (n = 99) were randomized to a single dose administration of ketamine 0.1 mg/kg (n = 18), ketamine 0.2 mg/kg (n = 20), ketamine 0.5 mg/kg (n = 22), ketamine 1.0 mg/kg (n = 20), or active placebo, midazolam 0.045 mg/kg (n = 19). Patients were stratified for BMI. For patients randomized to ketamine (n = 80), BMI was assessed as a continuous variable and also categorically (obese, overweight, not obese/overweight [reference]). The primary outcome measure was the change on the 6-item Hamilton Depression Rating Scale 24 hours after treatment. Outcomes at day 3 were also assessed. FINDINGS/RESULTS: The 6-item Hamilton Depression Rating Scale change scores at 24 hours were inversely associated with BMI (-0.28 ± 0.12, P = 0.02). With BMI operationalized categorically, both obese (-4.15 ± 1.41, P = 0.004) and overweight (-1.99 ± 1.14, P = 0.08) categories were inversely related to the 6-item Hamilton Depression Rating Scale change score at 24 hours, statistically significant for the obese category, as compared with the reference group. Similar but weaker findings were observed at 72 hours after infusion. IMPLICATIONS/CONCLUSIONS: Higher BMI and obesity were associated with a more robust acute antidepressant response to ketamine. This may have clinical relevance for a great number of patients who have both MDD and obesity. CLINICAL TRIAL REGISTRATION: NCT01920555.

Double-blind, placebo-controlled, proof-of-concept trial of a kappa-selective opioid receptor antagonist augmentation in treatment-resistant depression.

BACKGROUND: Kappa-opioid antagonism may possess antidepressant properties. We assessed, in a proof-of-concept pilot trial among patients with major depressive disorder with inadequate response to antidepressants, the efficacy of adjunctive CERC-501 (formerly LY2456302), a kappaselective opioid receptor antagonist. METHODS: In a Sequential Parallel Comparison Design study, patients were pre-randomized to: a) 10 mg/d of CERC-501 for 6 days, b) 20 mg/d of CERC-501 for 6 days, c) placebo for 3 days followed by 10 mg/d of CERC- 501 for 3 days, d) placebo for 3 days followed by 20 mg/d of CERC-501 for 3 days, or e) placebo for 6 days. RESULTS: The study was terminated early by the National Institute of Mental Health due to slow enrollment (N = 8). The weighted mean difference of changes (drug vs placebo) in the 6-item Hamilton Depression Rating Scale (HAMD-6) (primary outcome measure) (1.28), Montgomery-Åsberg Depression Rating Scale (MADRS) (2.33), Perceived Stress Scale (1.01), Symptoms of Depression Questionnaire (9.17), Positive Affect Scale (PAS) (6.39), Symptom Questionnaire (SQ) Depression scale (2.94), SQ Anger- Hostility scale (1.67), and Patient-Reported Outcomes Measurement Information System Satisfaction with Participation in Discretionary Social Activities (4.67) scores were all numerically but not statistically greater for CERC-501 than for placebo. CONCLUSIONS: Although the small sample size limits the ability to draw conclusions, results suggest that CERC-501 may have antidepressant effects. Additional studies are necessary to further explore these effects of CERC-501.

Efficacy of intravenous ketamine treatment in anxious versus nonanxious unipolar treatment-resistant depression.

OBJECTIVE: To examine the effect of high baseline anxiety on response to ketamine versus midazolam (active placebo) in treatment-resistant depression (TRD). METHODS: In a multisite, double-blind, placebo-controlled trial, 99 subjects with TRD were randomized to one of five arms: a single dose of intravenous ketamine 0.1, 0.2, 0.5, 1.0 mg/kg, or midazolam 0.045 mg/kg. The primary outcome measure was change in the six-item Hamilton Rating Scale for Depression (HAMD6). A linear mixed effects model was used to examine the effect of anxious depression baseline status (defined by a Hamilton Depression Rating Scale Anxiety-Somatization score ≥7) on response to ketamine versus midazolam at 1 and 3 days postinfusion. RESULTS: N = 45 subjects had anxious TRD, compared to N = 54 subjects without high anxiety at baseline. No statistically significant interaction effect was found between treatment group assignment (combined ketamine treatment groups versus midazolam) and anxious/nonanxious status on HAMD6 score at either days 1 or 3 postinfusion (Day 1: F(1, 84) = 0.02, P = 0.88; Day 3: F(1, 82) = 0.12, P = 0.73). CONCLUSION: In contrast with what is observed with traditional antidepressants, response to ketamine may be similar in both anxious and nonanxious TRD subjects. These pilot results suggest the potential utility of ketamine in the treatment of anxious TRD.

Humanitarian space and well-being: effectiveness of training on a psychosocial intervention for host community-refugee interaction.

Social and fieldworkers face enormous challenges in assisting millions of Syrian refugees in Lebanon since the Syrian war in 2011. We sought to assess the feasibility and acceptability of an adapted version of the SMART-3RP (Stress Management Relaxation Response Resilience Training) training to address the emotional and physical burden on the humanitarian field. Data were collected using the Symptom Checklist-90 (SCL-90), blood pressure, pulse and a brief qualitative survey at months 0, 3, 6 and 9. We compared mean SCL-90 scores and physiological measures from these time points and subjected qualitative data to a thematic analysis. Mean values of all measures decreased from months 0 to 9, with significance in SCL-90 changes increasing at each visit. Qualitative themes included decreased stress, increased positivity and problem-solving skills, interpersonal and personal benefits of mindfulness practice and the need to continue and expand the programme. Qualitative and quantitative analyses showed a decrease in stress perception and blood pressure, demonstrating the physiological benefits of mind body approaches. We highlight the importance of self-care for humanitarian workers as the basis for the mission's success. We invite additional research to confirm these findings and their implications for the humanitarian field.

Racial/Ethnic Differences in Insomnia Trajectories Among U.S. Older Adults.

OBJECTIVES: Insomnia is reported to be more prevalent in minority racial/ethnic groups. Little is known, however, about racial/ethnic differences in changes in insomnia severity over time, particularly among older adults. We examined racial/ethnic differences in trajectories of insomnia severity among middle-aged and older adults. DESIGN: Data were drawn from five waves of the Health and Retirement Study (2002-2010), a nationally representative longitudinal biennial survey of adults aged > 50 years. SETTING: Population-based. PARTICIPANTS: 22,252 participants from non-Hispanic white, non-Hispanic black, Hispanic, and other racial/ethnic groups. MEASUREMENTS: Participants reported the severity of four insomnia symptoms; summed scores ranged from 4 (no insomnia) to 12 (severe insomnia). We assessed change in insomnia across the five waves as a function of race/ethnicity. RESULTS: Across all participants, insomnia severity scores increased 0.19 points (95% CI: 0.14-0.24; t = 7.52; design df = 56; p < 0.001) over time after adjustment for sex, race/ethnicity, education, and baseline age. After adjusting for the number of accumulated health conditions and body mass index, this trend decreased substantially and even changed direction (B = -0.24; 95% CI: -0.29 to -0.19; t = -9.22; design df = 56; p < 0.001). The increasing trajectory was significantly more pronounced in Hispanics compared with non-Hispanic whites, even after adjustment for number of accumulated health conditions, body mass index, and number of depressive symptoms. CONCLUSIONS: Although insomnia severity increases with age-largely due to the accumulation of health conditions-this trend appears more pronounced among Hispanic older adults than in non-Hispanic whites. Further research is needed to determine the reasons for a different insomnia trajectory among Hispanics.

Personality and cognitive decline in the Baltimore Epidemiologic Catchment Area follow-up study.

OBJECTIVE: To determine the association between personality domains and 11-year cognitive decline in a sample from a population-based study. METHOD: Data from Waves 3 (1993-1996) and 4 (2003-2004) of the Baltimore cohort of the Epidemiologic Catchment Area (ECA) study were used for analyses. The sample included 561 adults (mean age ± SD: 45.2 ± 10.78 years) who completed the NEO Personality Inventory-Revised prior to Wave 4. Participants also completed the Mini-Mental State Examination (MMSE) and immediate and delayed word recall tests at Wave 3, and at Wave 4, 10.9 ± 0.6 years later. RESULTS: In models adjusted for baseline cognitive performance, demographic characteristics, medical conditions, depressive symptoms, and psychotropic medication use, each 10-point increase in Neuroticism T-scores was associated with a 0.15-point decrease in MMSE scores (B = -0.15, 95% confidence interval [CI]: -0.30, -0.01), whereas each 10-point increase in Conscientiousness T-scores was associated with a 0.18-point increase on the MMSE (B = 0.18, 95% CI: 0.04, 0.32) and a 0.21-point increase in immediate recall (B = 0.21, 95% CI: 0.003, 0.41) between baseline and follow-up. CONCLUSION: Findings suggest that greater Neuroticism is associated with decline, and greater Conscientiousness is associated with improvement in performance on measures of general cognitive function and memory in adults. Further studies are needed to determine the extent to which personality traits in midlife are associated with clinically significant cognitive outcomes in older adults, such as mild cognitive impairment and dementia, and to identify potential mediators of the association between personality and cognitive trajectories.

Early maternal depressive symptoms and child growth trajectories: a longitudinal analysis of a nationally representative US birth cohort.

BACKGROUND: Maternal depressive symptoms are negatively associated with early child growth in developing countries; however, few studies have examined this relation in developed countries or used a longitudinal design with data past the second year of the child's life. We investigated if and when early maternal depressive symptoms affect average growth in young children up to age 6 in a nationally representative sample of US children. METHODS: Using data from 6,550 singleton births from the Early Childhood Longitudinal Study -- Birth Cohort (ECLS-B), we fit growth trajectory models with random effects to examine the relation between maternal depressive symptoms at 9 months based on the twelve-item version of the Center for Epidemiologic Studies Depression Scale (CES-D) and child height and body mass index (BMI) to age 6 years. RESULTS: Mothers with moderate/severe depressive symptoms at 9 months postpartum had children with shorter stature at this same point in time [average 0.26 cm shorter; 95% CI: 5 cm, 48 cm] than mothers without depressive symptoms; children whose mothers reported postpartum depressive symptoms remained significantly shorter throughout the child's first 6 years. CONCLUSIONS: Results suggest that the first year postpartum is a critical window for addressing maternal depressive symptoms in order to optimize child growth. Future studies should investigate the role of caregiving and feeding practices as potential mechanisms linking maternal depressive symptoms and child growth trajectories.

Antidepressants in the acute treatment of post-traumatic stress disorder in adults: a systematic review and meta-analysis.

Currently, there are few pharmacotherapy options for clinicians treating post-traumatic stress disorder (PTSD), and antidepressants are usually the medication of choice. This meta-analysis aimed to review the efficacy of antidepressants in the acute treatment of PTSD in adults while investigating the contribution of study design and placebo response to the findings of these studies. Randomized, double-blind, placebo-controlled clinical trials that compared antidepressants with placebo for acute treatment of PTSD were selected. Standardized mean difference (SMD) in change in Clinician-Administered PTSD Scale scores were pooled after examining for heterogeneity. A random-effects meta-analysis was performed. Twenty-nine antidepressant-placebo comparisons, involving 4575 subjects, were analyzed. The SMD among all studies was 0.25, a small to medium effect size, lower than that in studies of antidepressants in adult major depressive disorder. The SMDs for low and high mean placebo responses, were 0.27 and 0.22, respectively. The overall SMD for paroxetine studies was in the moderate range (0.43) and that for sertraline studies was in the small range (0.12). Our findings suggest that antidepressants have modest efficacy in alleviating PTSD symptoms. Patient-level meta-analyses are required to further explore the potential clinical relevance of sertraline for PTSD.

Sleep, function and HIV: a multi-method assessment.

Amongst HIV+ individuals, sleep complaints have been recognized as common and debilitating; but have rarely been formally assessed or compared to controls using validated sleep tools. In this study we conducted structured interview for sleep disorders, polysomnography, 2-week home (ambulatory) monitoring and validated sleep/functional questionnaires. 56 % (14/25) of HIV+ participants and 0 % (0/19) of controls fulfilled the diagnostic criteria for insomnia. Insomnia severity scores were correlated with fatigue and anxiety symptoms. Sleep latency on 2-week actigraphy was significantly longer (P = 0.027) for HIV+ participants and associated with lower MOS-HIV scores. Sleep quality was significantly reduced in HIV+ participants based on validated questionnaires of overall sleep quality (P = 0.0017) and insomnia related symptoms (P < 0.001) even after adjusting for education and affective symptoms. HIV+ individuals are suffering with under-diagnosed sleep disorders that are negatively impacting quality of life and functional capabilities. Further studies aimed at improving recognition of sleep disorders and implementation of efficacious medical and behavioral treatment could improve functioning and disease management.

A United Nations General Assembly Special Session for mental, neurological, and substance use disorders: the time has come.

Mental, neurological, and substance use (MNS) disorders are leading causes of the global burden of disease and profoundly impact the social and economic well-being of individuals and communities. The majority of people affected by MNS disorders globally do not have access to evidence-based interventions and many experience discrimination and abuses of their human rights. A United Nations General Assembly Special Session (UNGASS) is needed to focus global attention on MNS disorders as a core development issue requiring commitments to improve access to care, promote human rights, and strengthen the evidence on effective prevention and treatment.

Economic evaluation of a task-shifting intervention for common mental disorders in India.

OBJECTIVE: To carry out an economic evaluation of a task-shifting intervention for the treatment of depressive and anxiety disorders in primary-care settings in Goa, India. METHODS: Cost-utility and cost-effectiveness analyses based on generalized linear models were performed within a trial set in 24 public and private primary-care facilities. Subjects were randomly assigned to an intervention or a control arm. Eligible subjects in the intervention arm were given psycho-education, case management, interpersonal psychotherapy and/or antidepressants by lay health workers. Subjects in the control arm were treated by physicians. The use of health-care resources, the disability of each subject and degree of psychiatric morbidity, as measured by the Revised Clinical Interview Schedule, were determined at 2, 6 and 12 months. FINDINGS: Complete data, from all three follow-ups, were collected from 1243 (75.4%) and 938 (81.7%) of the subjects enrolled in the study facilities from the public and private sectors, respectively. Within the public facilities, subjects in the intervention arm showed greater improvement in all the health outcomes investigated than those in the control arm. Time costs were also significantly lower in the intervention arm than in the control arm, whereas health system costs in the two arms were similar. Within the private facilities, however, the effectiveness and costs recorded in the two arms were similar. CONCLUSION: Within public primary-care facilities in Goa, the use of lay health workers in the care of subjects with common mental disorders was not only cost-effective but also cost-saving.

Infant malnutrition predicts conduct problems in adolescents.

OBJECTIVES: The purpose of this study was to compare the prevalence of conduct problems in a well-documented sample of Barbadian adolescents malnourished as infants and a demographic comparison group and to determine the extent to which cognitive impairment and environmental factors account for this association. METHODS: Behavioral symptoms were assessed using a 76-item self-report scale in 56 Barbadian youth (11-17 years of age) with histories of protein-energy malnutrition (PEM) limited to the first year of life and 60 healthy classmates. Group comparisons were carried out by longitudinal and cross-sectional multiple regression analyses at 3 time points in childhood and adolescence. RESULTS: Self-reported conduct problems were more prevalent among previously malnourished youth (P < 0.01). Childhood IQ and home environmental circumstances partially mediated the association with malnutrition. Teacher-reported classroom behaviors at earlier ages were significantly correlated with youth conduct problems, confirming the continuity of conduct problems through childhood and adolescence. DISCUSSION: Self-reported conduct problems are elevated in children and adolescents with histories of early childhood malnutrition. Later vulnerability to increased conduct problems appears to be mediated by the more proximal neurobehavioral effects of the malnutrition on cognitive function and by adverse conditions in the early home environment.

Antidepressants in children and adolescents with major depressive disorder and the influence of placebo response: A meta-analysis.

BACKGROUND: There are few available antidepressants for pediatric Major Depressive Disorder (MDD). The objective of this systematic review and meta-analysis was to review industry-funded studies of antidepressants in children and adolescents with MDD, and to better understand the contribution of study design and placebo response to the findings of these studies. METHODS: Randomized, double-blind, placebo-controlled clinical trials that compared antidepressant with placebo for the acute treatment of MDD in children and/or adolescents were selected. Estimates of the standardized mean difference (SMD) in change in Children's Depression Rating Scale-Revised scores were pooled, after examining for heterogeneity. A random-effects meta-analysis was completed. RESULTS: Thirty-four antidepressant-placebo comparisons, involving 6161 subjects, were included. The SMD among all studies was 0.12 (CI 0.08, 0.17; p < 0.001), a very small effect size, lower than that seen in studies of adults with MDD. When the meta-analysis was limited to studies with a low mean placebo response, the SMD increased to 0.19 and further increased to 0.22 when studies with at least a 50% chance of receiving placebo were included. LIMITATIONS: Many studies focused on older children and younger adolescents. Our findings may not reflect antidepressant efficacy in older adolescents. CONCLUSIONS: The modest SMD identified in this analysis may reflect study design factors and the application of antidepressants developed for adults to pediatric patients. Given the urgent clinical need for more pediatric MDD treatments, the influence of placebo response and the need for drug development tailored to this population should be considered in pediatric MDD trial design.

Rapidity of Symptom Improvement With Intranasal Esketamine for Major Depressive Disorder: A Systematic Review and Meta-Analysis.

Objective: Rapid-acting treatment options are needed for major depressive disorder (MDD). The objective of this systematic review and meta-analysis was to estimate the magnitude of the treatment effect for intranasal esketamine over placebo at 24 hours after the first dose and at endpoint.Data Sources: PubMed, abstracts of major psychiatric meetings, and ClinicalTrials.gov were searched up to November 2020 with no language constraints, cross-referencing the term intranasal with esketamine and randomized.Study Selection: Of 27 studies reviewed, 8 articles, with a total of 1,437 patients with MDD, met study criteria and were included in the meta-analysis.Data Extraction: Randomized, double-blind clinical trials comparing adjunctive treatment of standard antidepressants with intranasal esketamine for MDD, using intranasal placebo augmentation as a comparator, were selected.Results: Estimates of the standardized mean difference (SMD) in change scores were pooled after examining for homogeneity using the test statistic proposed by DerSimonian and Laird. Findings of the random effects model were presented. Augmentation of standard antidepressants with intranasal esketamine resulted in greater Montgomery-Asberg Depression Rating Scale (MADRS) score reduction than adjunctive intranasal placebo at 24 hours. Across the trials, the SMD was 0.34 (95% CI = 0.11 to 0.46, P < .0001) with a 2.9-point greater mean MADRS score reduction following intranasal esketamine versus active control plus intranasal saline. A similar finding was evident at endpoint.Conclusions: This updated systematic review and meta-analysis found that augmentation of antidepressants with intranasal esketamine was statistically and clinically more effective in reducing depression severity than augmentation with placebo, at both 24 hours and study endpoint. Future studies are needed to evaluate dose-response relationship for esketamine.

The effect of single administration of intravenous ketamine augmentation on suicidal ideation in treatment-resistant unipolar depression: Results from a randomized double-blind study.

This study aimed to assess the effect of a single infusion of intravenous (IV) ketamine on suicidal ideation in patients with treatment-resistant depression (TRD). Patients with TRD were randomized in a double-blind fashion to a single infusion of IV ketamine or IV midazolam placebo. Suicidal ideation was measured using the Montgomery-Asberg Depression Rating Scale (MADRS) suicide item at 3, 5, 7, 14 and 30 days post infusion. Clinically significant suicidal ideation was defined as a MADRS suicide item score ≥2. Forty patients who received IV ketamine and 16 who received IV midazolam had suicide item scores of ≥2 at baseline (IV ketamine group mean 2.90±0.74; IV midazolam group 2.69±0.70). The mean suicide scores of these groups differed significantly from each other on day 30; the IV ketamine group had a lower mean score than controls (2.03±1.59 vs. 3.00±1.41, t-test p = 0.049; Hedges' g 0.71). Among patients with a suicide score of ≥2 at baseline and <2 at day 3, the two groups did not differ significantly on mean scores changes at days 3, 5, 7, 14 or 30. Recurrence of suicidal ideation was extensive in both treatment groups. A single infusion of IV ketamine may reduce suicidal ideation in TRD out to 30 days post infusion, but early anti-suicidal effects appear to diminish rapidly. This post-hoc analysis was not powered to compare different doses of ketamine. A single infusion of IV ketamine might have a role as an adjunct to standard treatments in patients with TRD and suicidal ideation. Trial registration: NCT01920555.