Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) through non-specialist providers and telemedicine: a study protocol for a non-inferiority randomized controlled trial.

BACKGROUND: Depression and anxiety impact up to 1 in 5 pregnant and postpartum women worldwide. Yet, as few as 20% of these women are treated with frontline interventions such as evidence-based psychological treatments. Major barriers to uptake are the limited number of specialized mental health treatment providers in most settings, and problems with accessing in-person care, such as childcare or transportation. Task sharing of treatment to non-specialist providers with delivery on telemedicine platforms could address such barriers. However, the equivalence of these strategies to specialist and in-person models remains unproven. METHODS: This study protocol outlines the Scaling Up Maternal Mental healthcare by Increasing access to Treatment (SUMMIT) randomized trial. SUMMIT is a pragmatic, non-inferiority test of the comparable effectiveness of two types of providers (specialist vs. non-specialist) and delivery modes (telemedicine vs. in-person) of a brief, behavioral activation (BA) treatment for perinatal depressive and anxiety symptoms. Specialists (psychologists, psychiatrists, and social workers with ≥ 5 years of therapy experience) and non-specialists (nurses and midwives with no formal training in mental health care) were trained in the BA protocol, with the latter supervised by a BA expert during treatment delivery. Consenting pregnant and postpartum women with Edinburgh Postnatal Depression Scale (EPDS) score of ≥ 10 (N = 1368) will be randomized to one of four arms (telemedicine specialist, telemedicine non-specialist, in-person specialist, in-person non-specialist), stratified by pregnancy status (antenatal/postnatal) and study site. The primary outcome is participant-reported depressive symptoms (EPDS) at 3 months post-randomization. Secondary outcomes are maternal symptoms of anxiety and trauma symptoms, perceived social support, activation levels and quality of life at 3-, 6-, and 12-month post-randomization, and depressive symptoms at 6- and 12-month post-randomization. Primary analyses are per-protocol and intent-to-treat. The study has successfully continued despite the COVID-19 pandemic, with needed adaptations, including temporary suspension of the in-person arms and ongoing randomization to telemedicine arms. DISCUSSION: The SUMMIT trial is expected to generate evidence on the non-inferiority of BA delivered by a non-specialist provider compared to specialist and telemedicine compared to in-person. If confirmed, results could pave the way to a dramatic increase in access to treatment for perinatal depression and anxiety. TRIAL REGISTRATION: ClinicalTrials.gov NCT04153864 . Registered on November 6, 2019.

Repetitive transcranial magnetic stimulation for the treatment of postpartum depression.

BACKGROUND: Postpartum depression (PPD) is a common and gravely disabling health concern. Repetitive transcranial magnetic stimulation (rTMS) is an FDA approved treatment for major depression and may be a valuable tool in the treatment of PPD. The treatment effect of rTMS is rapid, generally well tolerated, without systemic effects, and without medication exposure to a fetus and/or breastfed infant. METHODS: Six women with PPD received 20 sessions of 10 Hz rTMS over the left dorsolateral prefrontal cortex (DLPFC) over a 4 week period. Psychiatric rating scales (BDI, EPDS, STATI), cognitive assessments (MMSE, Trails B, List Generation) and breastfeeding practices were surveyed at baseline and post rTMS treatment. BDI and EPDS were obtained weekly, as well as 3 months and 6 months post study conclusion. RESULTS: Average BDI, EPDS, and STAI scores declined over the 4-week duration of rTMS treatment. Of the six patients, four achieved remission as assessed by EPDS and one achieved remission and two responded as assessed by BDI. Mean BDI and EPDS scores at 3 and 6 months follow-up remained below levels at study entry. No evidence of cognitive changes or breastfeeding disruptions. LIMITATIONS: This was an exploratory study with small sample size with no sham control arm. Daily administration of rTMS provides potential for confounding of behavioral activation in the otherwise often isolative postpartum period. CONCLUSIONS: rTMS was safe and well tolerated among participants with evidence of sustained improvements in depression and anxiety scores. This study supports rTMS as a promising non-pharmacologic treatment modality for perinatal depression.

Adverse life events, psychiatric history, and biological predictors of postpartum depression in an ethnically diverse sample of postpartum women.

BACKGROUND: Race, psychiatric history, and adverse life events have all been independently associated with postpartum depression (PPD). However, the role these play together in Black and Latina women remains inadequately studied. Therefore, we performed a case-control study of PPD, including comprehensive assessments of symptoms and biomarkers, while examining the effects of genetic ancestry. METHODS: We recruited our sample (549 cases, 968 controls) at 6 weeks postpartum from obstetrical clinics in North Carolina. PPD status was determined using the MINI-plus. Psychiatric history was extracted from medical records. Participants were administered self-report instruments to assess depression (Edinburgh Postnatal Depression Scale) and adverse life events. Levels of estradiol, progesterone, brain-derived neurotrophic factor, oxytocin, and allopregnanalone were assayed. Principal components from genotype data were used to estimate genetic ancestry and logistic regression was used to identify predictors of PPD. RESULTS: This population was racially diverse (68% Black, 13% Latina, 18% European). Genetic ancestry was not a predictor of PPD. Case status was predicted by a history of major depression (p = 4.01E-14), lifetime anxiety disorder diagnosis (p = 1.25E-34), and adverse life events (p = 6.06E-06). There were no significant differences between groups in any hormones or neurosteroids. CONCLUSIONS: Psychiatric history and multiple exposures to adverse life events were significant predictors of PPD in a population of minority and low-income women. Genetic ancestry and hormone levels were not predictive of case status. Increased genetic vulnerability in conjunction with risk factors may predict the onset of PPD, whereas genetic ancestry does not appear predictive.

Adverse life events increase risk for postpartum psychiatric episodes: A population-based epidemiologic study.

BACKGROUND: Trauma histories may increase risk of perinatal psychiatric episodes. We designed an epidemiological population-based cohort study to explore if adverse childhood experiences (ACE) in girls increases risk of later postpartum psychiatric episodes. METHODS: Using Danish registers, we identified women born in Denmark between January 1980 and December 1998 (129,439 childbirths). Exposure variables were ACE between ages 0 and 15 including: (1) family disruption, (2) parental somatic illness, (3) parental labor market exclusion, (4) parental criminality, (5) parental death, (6) placement in out-of-home care, (7) parental psychopathology excluding substance use, and (8) parental substance use disorder. Primary outcome was first occurrence of in- or outpatient contact 0-6 months postpartum at a psychiatric treatment facility with any psychiatric diagnoses, ICD-10, F00-F99 (N = 651). We conducted survival analyses using Cox proportional hazard regressions of postpartum psychiatric episodes. RESULTS: Approximately 52% of the sample experienced ACE, significantly increasing risk of any postpartum psychiatric diagnosis. Highest risks were observed among women who experienced out-of-home placement, hazard ratio (HR) 2.57 (95% CI: 1.90-3.48). Women experiencing two adverse life events had higher risks of postpartum psychiatric diagnosis HR: 1.88 (95% CI: 1.51-2.36), compared to those with one ACE, HR: 1.24 (95% CI: 1.03-49) and no ACE, HR: 1.00 (reference group). CONCLUSIONS: ACE primarily due to parental psychopathology and disability contributes to increased risk of postpartum psychiatric episodes; and greater numbers of ACE increases risk for postpartum psychiatric illness with an observed dose-response effect. Future work should explore genetic and environmental factors that increase risk and/or confer resilience.

Obstetrical, pregnancy and socio-economic predictors for new-onset severe postpartum psychiatric disorders in primiparous women.

BACKGROUND: Childbirth is a potent trigger for the onset of psychiatric illness in women including postpartum depression (PPD) and postpartum psychosis (PP). Medical complications occurring during pregnancy and/or childbirth have been linked to postpartum psychiatric illness and sociodemographic factors. We evaluated if pregnancy and obstetrical predictors have similar effects on different types of postpartum psychiatric disorders. METHOD: A population-based cohort study using Danish registers was conducted in 392 458 primiparous women with a singleton delivery between 1995 and 2012 and no previous psychiatric history. The main outcome was first-onset postpartum psychiatric episodes. Incidence rate ratios (IRRs) were calculated for any psychiatric contact in four quarters for the first year postpartum. RESULTS: PPD and postpartum acute stress reactions were associated with pregnancy and obstetrical complications. For PPD, hyperemesis gravidarum [IRR 2.69, 95% confidence interval (CI) 1.93-3.73], gestational hypertension (IRR 1.84, 95% CI 1.33-2.55), pre-eclampsia (IRR 1.45, 95% CI 1.14-1.84) and Cesarean section (C-section) (IRR 1.32, 95% CI 1.13-1.53) were associated with increased risk. For postpartum acute stress, hyperemesis gravidarum (IRR 1.93, 95% CI 1.38-2.71), preterm birth (IRR 1.51, 95% CI 1.30-1.75), gestational diabetes (IRR 1.42, 95% CI 1.03-1.97) and C-section (IRR 1.36, 95% CI 1.20-1.55) were associated with increased risk. In contrast, risk of PP was not associated with pregnancy or obstetrical complications. CONCLUSIONS: Pregnancy and obstetrical complications can increase the risk for PPD and acute stress reactions but not PP. Identification of postpartum women requiring secondary care is needed to develop targeted approaches for screening and treatment. Future work should focus on understanding the contributions of psychological stressors and underlying biology on the development of postpartum psychiatric illness.

Maternal Childhood Sexual Trauma and Early Parenting: Prenatal and Postnatal Associations.

Existing research suggests that approximately 19% of females experience childhood sexual trauma (CST). Little is known, however, about the parenting behaviour of mothers who have experienced CST. Using propensity-matched controls, the present study examines prenatal psychosocial distress, postnatal depressive symptomatology, and caregiving behaviours of women reporting CST at or before the age of 14. Data for these analyses were obtained from mother reports and from observational protocols from a longitudinal study of low-income, rural families. Propensity score methodology was used to create a contrast group matched on family of origin variables in an effort to isolate and examine the long-term associations of CST beyond the effects of other childhood adversities such as poverty. Study findings provide evidence that women with CST histories report greater prenatal psychosocial distress compared to women without trauma histories. Findings further provide evidence for a spillover process from prenatal distress to the broader caregiving system including less sensitive parenting through postnatal depressive symptoms for women with CST histories. These results highlight the importance of screening for CST and psychosocial distress and depression prenatally. Interventions for women with CST histories and directions for future study are proposed.

The impact of education, country, race and ethnicity on the self-report of postpartum depression using the Edinburgh Postnatal Depression Scale.

BACKGROUND: Universal screening for postpartum depression is recommended in many countries. Knowledge of whether the disclosure of depressive symptoms in the postpartum period differs across cultures could improve detection and provide new insights into the pathogenesis. Moreover, it is a necessary step to evaluate the universal use of screening instruments in research and clinical practice. In the current study we sought to assess whether the Edinburgh Postnatal Depression Scale (EPDS), the most widely used screening tool for postpartum depression, measures the same underlying construct across cultural groups in a large international dataset. METHOD: Ordinal regression and measurement invariance were used to explore the association between culture, operationalized as education, ethnicity/race and continent, and endorsement of depressive symptoms using the EPDS on 8209 new mothers from Europe and the USA. RESULTS: Education, but not ethnicity/race, influenced the reporting of postpartum depression [difference between robust comparative fit indexes (∆*CFI) 0.01), but not between European countries (∆*CFI < 0.01). CONCLUSIONS: Investigators and clinicians should be aware of the potential differences in expression of phenotype of postpartum depression that women of different educational backgrounds may manifest. The increasing cultural heterogeneity of societies together with the tendency towards globalization requires a culturally sensitive approach to patients, research and policies, that takes into account, beyond rhetoric, the context of a person's experiences and the context in which the research is conducted.

Perinatal psychiatric episodes: a population-based study on treatment incidence and prevalence.

Perinatal psychiatric episodes comprise various disorders and symptom severity, which are diagnosed and treated in multiple treatment settings. To date, no studies have quantified the incidence and prevalence of perinatal psychiatric episodes treated in primary and secondary care, which we aimed to do in the present study. We designed a descriptive prospective study and included information from Danish population registers to study first-time ever and recurrent psychiatric episodes during the perinatal period, including treatment at psychiatric facilities and general practitioners (GPs). This was done for all women who had records of one or more singleton births from 1998 until 2012. In total, we had information on 822 439 children born to 491 242 unique mothers. Results showed first-time psychiatric episodes treated at inpatient facilities were rare during pregnancy, but increased significantly shortly following childbirth (0.02 vs 0.25 per 1000 births). In comparison, first-time psychiatric episodes treated at outpatient facilities were more common, and showed little variation across pregnancy and postpartum. For every single birth resulting in postpartum episodes treated at inpatient psychiatric facilities, 2.5 births were followed by an episode treated at outpatient psychiatric facility and 12 births by GP-provided pharmacological treatment. We interpret our results the following way: treated severe and moderate psychiatric disorders have different risk patterns in relation to pregnancy and childbirth, which suggests differences in the underlying etiology. We further speculate varying treatment incidence and prevalence in pregnancy vs postpartum may indicate that the current Diagnostic and Statistical Manual of Mental Disorders-5 peripartum specifier not adequately describes at-risk periods across moderate and severe perinatal psychiatric episodes.

Treatment of severe perinatal mood disorders on a specialized perinatal psychiatry inpatient unit.

Perinatal patients with bipolar and psychotic mood disorder exacerbations are challenging to treat and often receive suboptimal care. We sought to examine the treatment patterns and outcomes on one of the only US-based Perinatal Psychiatry Inpatient Units (PPIU). Perinatal patients admitted to the PPIU completed self-report measures at admission and before discharge. Retrospective chart reviews extracted history, diagnoses (current and past), and medication treatment. Patients who had discharge diagnoses of bipolar disorder, major depression with psychotic features, or postpartum psychosis were included. Forty-seven met the diagnostic inclusion criteria. Over an average length of stay (ALOS) of 9.96 days, there was significant improvement in depressive and anxiety symptoms and daily functioning (Work and Social Adjustment Scale). Psychiatric comorbidity was common. Polypharmacy was utilized in 87 %. The most common medications prescribed at discharge were antipsychotics, alone or in combination with mood stabilizers or antidepressants. ECT was performed in 10 % of cases. The complexity of patients with severe mood disorders or psychosis admitted to the PPIU supports individualized treatment plans that address both primary diagnosis and psychiatric comorbidities. Our results provide important information that can be disseminated to others to improve clinical outcomes for severe perinatal mood disorders.

Obstetric and gynecologic problems associated with eating disorders.

OBJECTIVE: This article summarizes the literature on obstetric and gynecologic complications associated with eating disorders. METHOD: We performed a comprehensive search of the current literature on obstetric and gynecologic complications associated with eating disorders using PubMed. More recent randomized-controlled trials and larger data sets received priority. We also chose those that we felt would be the most relevant to providers. RESULTS: Common obstetric and gynecologic complications for women with eating disorders include infertility, unplanned pregnancy, miscarriage, poor nutrition during pregnancy, having a baby with small head circumference, postpartum depression and anxiety, sexual dysfunction and complications in the treatment for gynecologic cancers. There are also unique associations by eating disorder diagnosis, such as earlier cessation of breastfeeding in anorexia nervosa; increased polycystic ovarian syndrome in bulimia nervosa; and complications of obesity as a result of binge eating disorder. DISCUSSION: We focus on possible biological and psychosocial factors underpinning risk for poor obstetric and gynecological outcomes in eating disorders. Understanding these factors may improve both our understanding of the reproductive needs of women with eating disorders and their medical outcomes. We also highlight the importance of building multidisciplinary teams to provide comprehensive care to women with eating disorders during the reproductive years.

Pre-eclampsia and first-onset postpartum psychiatric episodes: a Danish population-based cohort study.

BACKGROUND: Recent evidence suggests that postpartum psychiatric episodes may share similar etiological mechanisms with immune-related disorders. Pre-eclampsia is one of the most prevalent immune-related disorders of pregnancy. Multiple clinical features are shared between pre-eclampsia and postpartum psychiatric disorders, most prominently a strong link to first pregnancies. Therefore, we aimed to study if pre-eclampsia is a risk factor for first-onset postpartum psychiatric episodes. METHOD: We conducted a cohort study using the Danish population registry, with a total of 400 717 primiparous women with a singleton delivery between 1995 and 2011. First-lifetime childbirth was the main exposure variable and the outcome of interest was first-onset postpartum psychiatric episodes. The main outcome measures were monthly incidence rate ratios (IRRs), with the period 11-12 months after birth as the reference category. Adjustments were made for age, calendar period, reproductive history, and perinatal maternal health including somatic and obstetric co-morbidity. RESULTS: Primiparous women were at particularly high risk of first-onset psychiatric episodes during the first month postpartum [IRR 2.93, 95% confidence interval (CI) 2.53-3.40] and pre-eclampsia added to that risk (IRR 4.21, 95% CI 2.89-6.13). Having both pre-eclampsia and a somatic co-morbidity resulted in the highest risk of psychiatric episodes during the 3-month period after childbirth (IRR 4.81, 95% CI 2.72-8.50). CONCLUSIONS: We confirmed an association between pre-eclampsia and postpartum psychiatric episodes. The possible explanations for this association, which are not mutually exclusive, include the psychological impact of a serious medical condition such as pre-eclampsia and the neurobiological impact of pre-eclampsia-related vascular pathology and inflammation.

Oxytocin and HPA stress axis reactivity in postpartum women.

BACKGROUND: Lactation is thought to buffer stress reactivity via oxytocin (OT). Dysregulation of the HPA axis has been reported in women with postpartum depression (PPD). The co-occurrence of PPD and lactation failure suggests that abnormalities in OT signaling may play a role in PPD. We hypothesized that abnormal OT signaling is implicated in dysregulated HPA axis reactivity among postpartum women with mood symptoms. In a prospective perinatal cohort, we tested associations between OT levels during breastfeeding and stress reactivity. METHODS: We recruited 52 pregnant women who intended to breastfeed, among whom 47 underwent a standardized stressor, the Trier Social Stress Test (TSST), at 8 weeks postpartum. 39 were breastfeeding at time of TSST. We assessed mood symptoms using validated instruments and defined as symptomatic women with EPDS ≥ 10 and/or Spielberger ≥ 34. Following IV placement for blood draws, women breastfed their infants and then underwent the TSST. Mothers' hormone responses were quantified. RESULTS: Among symptomatic breastfeeding women (N=11; asymptomatic N=28), we found lower OT levels during breastfeeding (p<0.05) and higher CORT levels (p<0.05) both during breastfeeding and the TSST, as compared to asymptomatic breastfeeding women. In a mixed effects model examining CORT reactivity by symptom group and OT AUC, we observed a paradoxical response in symptomatic breastfeeding women during the TSST (group × time × OT AUC p<0.05); higher OT AUC was associated with higher CORT. CONCLUSIONS: In all breastfeeding women, the surge of OT during feeding appears to buffer subsequent stress-induced CORT secretion. However, in symptomatic breastfeeding women, we found a positive correlation between OT AUC and CORT, instead of the expected negative correlation, which we found among asymptomatic women.

St. John's Wort: clinical status in psychiatry.

Depression and anxiety are among the top 10 health problems for which complementary and alternative therapies (CATs) are most frequently used, and medicinal herbs are among the most popular of these treatments. St. John's wort (Hypericum perforatum) is a perennial herb that has become a widely used depression therapy. Extracts of hypericum have shown affinity for receptors within multiple neurochemical systems. The primary active substance responsible for the antidepressant effect is not well defined, but most work has concentrated specifically on the hypericin and hyperforin components. Although hypericum has demonstrated significant antidepressant and antianxiety effects in multiple studies, there are several recent studies that do not support the previous evidence. In all reported studies, hypericum extracts have been well tolerated. In addition, new psychiatric uses for hypericum in obsessive-compulsive disorder, generalized anxiety disorder, menopausal symptoms, and alcohol dependence have been reported. Because patients are choosing to pursue CAT as a first-line therapy, psychiatrists will need to have a better understanding of phytomedicines used for treating depression and anxiety, and thus be better prepared to serve as effective allies of their patients.

Completeness of response and quality of life in mood and anxiety disorders.

Mental health care has traditionally focused on the need to document relief of specific symptoms of a psychiatric disorder, as well as how the patient functions in social roles. Recently, there has been increased attention paid to the issue of quality of life (QOL) and psychiatric illness. There has been a growing recognition that different treatment options may vary in their effects on the patient's ability to function in multiple life domains. Studies focusing on the QOL in patients suffering from mood and anxiety disorders have become more prevalent. Depression and anxiety disorders impose a substantial cost on society in terms of both psychiatric service costs as well as the loss of the individual to society through lost work production. However, a change in the severity of depression or anxiety often correlates with a change in disability and health service utilization. Lately, there have been a number of treatment studies of anxiety and depressive disorders that have examined the effect of treatment on QOL. Although treatment may reduce the severity and frequency of target symptoms, the patient's assessment of QOL helps to differentiate a true treatment response and remission from a partial response. The evaluation of what constitutes an adequate treatment response or remission is complicated and likely requires multiple assessment instruments in order to develop a complete understanding. In both anxiety and depressive disorders, the patient suffers from impaired functioning, which results in increased healthcare utilization. Because these patients do respond to treatment, the idea of "wellness" as a high end state treatment outcome should be an important consideration when selecting a treatment option.

Symptom-specific effects of fluoxetine in post-traumatic stress disorder.

The selective serotonin reuptake inhibitors have become a first line treatment for post-traumatic stress disorder (PTSD). In a recent double-blind study in civilians, fluoxetine produced clinically and statistically significant effects on all general measures of PTSD. We examined the specific effects of fluoxetine versus placebo in the above mentioned study of PTSD clusters and individual symptoms. Individuals were included if they met criteria for PTSD according to the Structured Clinical Interview for DSM-III-R (SCID). Symptoms were assessed at sequential time points by the Structured Interview for PTSD (SIP), a clinician interview based assessment, and a self-report scale, the Davidson Trauma Scale (DTS). A total of 53 patients were included in the analysis. On the SIP and DTS, fluoxetine was found to produce statistically significant changes on all clusters. Significant effects for fluoxetine were noted on 10 items of the DTS, and 8 items of the SIP. The SIP and DTS had 6 items in common that were significant. Fluoxetine exerts a broad spectrum effect in reducing all the symptom clusters of PTSD in this sample. The symptoms of being physically upset at reminders of the trauma, avoiding thoughts of the trauma, having difficulty enjoying things, feeling distant/estranged, having a sense of foreshortened future, and impaired concentration, were the symptoms most responsive to the effects of treatment with fluoxetine on both scales.

The underrecognition and undertreatment of depression: what is the breadth and depth of the problem?

Currently, 1 in 6 of the population will, at some point during their lives, suffer from major depression. By the year 2020, it has been estimated that major depression will be the second most important cause of disability worldwide. Major depression is associated not only with significant morbidity, but with comorbid chronic illnesses and lost productivity because of excess mortality and morbidity. The most important reason for the recognition and adequate treatment of depression is that symptoms can be effectively controlled. Despite this, patients are frequently neither recognized nor treated adequately. Underdiagnosis and undertreatment of major depression can be associated with factors relating to patients, their physicians, and the health care systems that provide their care. The treatment of depressed patients with appropriate agents, at appropriate doses, for appropriate periods of time, and incorporating appropriate nonpharmacologic strategies, is cost-effective. Since much of the management of depression occurs in primary care, approaches aimed at improving the overall management of the condition have a major role to play in lessening the burden of the disease.