Prophylactic Management of Women With Bipolar Disorder During Pregnancy and the Perinatal Period: Clinical Scenario-Based Practical Recommendations From A Group of Perinatal Psychiatry Authors.

ABSTRACT: Many women with bipolar disorder experience episodes of illness or relapses over the perinatal period, especially in the immediate postpartum period. Risks associated with treated/untreated psychopathologies and fetal exposure to bipolar medications make the management of bipolar disorder during these periods challenging for clinicians and patients. In light of the available effectiveness and reproductive safety data, the current clinical update based on the opinions of a group of international perinatal psychiatry authors recommends general considerations and specific management strategies for each possible clinical scenario, including mixed features, predominant polarity, diagnosis of subtypes of bipolar disorder, severity of previous episodes, and risk of recurrence of mood episodes.

C-Reactive protein concentrations in reproductive-aged women with major mood disorders.

To examine associations between high sensitivity C-reactive protein (CRP) concentrations and depressive symptoms in reproductive-aged women with mood disorders. Women (N = 86) with major depressive or bipolar disorder in a specialized mood disorders program provided plasma samples which were analyzed for CRP concentrations and categorized by tertiles (T1, low; T2, middle; T3 high). Depressive symptoms were assessed with the Inventory of Depressive Symptoms. We hypothesized that CRP concentrations would be significantly associated with the following: (1) depressive symptoms; (2) pregnancy, (3) body mass index, and (4) counts of white blood cells and absolute neutrophils and percentage of segmented neutrophils. The distribution of CRP concentrations was highly skewed with a median of 2.45 mg/L and an interquartile range 0.90 - 8.17 mg/L. Elevated plasma levels of CRP were not associated with depressive symptoms, which did not differ by tertile group either before or after adjusting for BMI, pregnancy status, and their interactions. Women in T3 had 5 times greater odds of pregnancy compared to women in T1 (p = .021). However, women in T2 had 11% greater BMI on average (p = 0.023), and women in T3 had 47% greater BMI compared to those in T1 (p < 0.001). Women in T3 had higher mean white blood cell counts than those in T1 and T2, the percentage of neutrophils was higher in T2 and T3 compared to T1, and women in T3 had higher absolute neutrophil counts compared to T1. CRP concentrations varied widely and were significantly elevated in reproductive-aged women with high BMI and current pregnancy, but not with depressive symptoms in this sample of depressed women.

The Gut Microbiome in Bipolar Disorder and Pharmacotherapy Management.

The gut microbiome is a complex and dynamic community of commensal, symbiotic, and pathogenic microorganisms that exist in a bidirectional relationship with the host. Bacterial functions in the gut play a critical role in healthy host functioning, and its disruption can contribute to many medical conditions. The relationship between gut microbiota and the brain has gained attention in mental health due to the mounting evidence supporting the association of gut bacteria with mood and behavior. Patients with bipolar disorder exhibit an increased frequency of gastrointestinal illnesses such as inflammatory bowel disease, which mechanistically has been linked to microbial community function. While the heterogeneity in microbial communities between individuals might be associated with disease risk, it may also moderate the efficacy or adverse effects associated with the use of medication. The following review highlights published evidence linking the function of gut microbiota both to bipolar disorder risk and to the effect of medications that influence microbiota, inflammation, and mood symptoms.

Risk-Benefit assessment of infant exposure to lithium through breast milk: a systematic review of the literature.

The continuation of lithium while breastfeeding is a controversial topic, and clinical recommendations vary. A systematic review was completed of available data on lithium and breastfeeding to determine the degree of lithium exposure through breast milk and assess the potential risk to the infant. Databases, including PubMed MEDLINE, Embase, PsycINFO, Web of Science, Scopus, and Cochrane CENTRAL Register of Controlled Trials databases, were searched for articles on lithium and breastfeeding from the start dates of the databases through December 2018. Articles were included if the report included at least one maternal serum/plasma and/or breast milk lithium concentration and one infant serum/plasma lithium concentration. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Twelve articles, all case reports, were selected for inclusion out of 441 articles that were found and 230 that were reviewed from the search. Data are limited on the safety of lithium continuation while breastfeeding. Among the adverse effects reported, it is difficult to differentiate poor outcomes from factors affecting infant health, concomitant medications, and gestational lithium exposure. Recommendations on whether to continue lithium while breastfeeding must be personalized to the individual woman and her infant.

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

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

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

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

Placentophagy: therapeutic miracle or myth?

Postpartum women are consuming their placentas encapsulated, cooked, and raw for the prevention of postpartum depression (PPD), pain relief, and other health benefits. Placentophagy is supported by health advocates who assert that the placenta retains hormones and nutrients that are beneficial to the mother. A computerized search was conducted using PubMed, Medline Ovid, and PsychINFO between January 1950 and January 2014. Keywords included placentophagy, placentophagia, maternal placentophagia, maternal placentophagy, human placentophagia, and human placentophagy. A total of 49 articles were identified. Empirical studies of human or animal consumption of human placentas were included. Editorial commentaries were excluded. Animal placentophagy studies were chosen based on their relevance to human practice. Ten articles (four human, six animal) were selected for inclusion. A minority of women in developed countries perceive placentophagy to reduce PPD risk and enhance recovery. Experimental animal research in support of pain reduction has not been applied in humans. Studies investigating placenta consumption for facilitating uterine contraction, resumption of normal cyclic estrogen cycle, and milk production are inconclusive. The health benefits and risks of placentophagy require further investigation of the retained contents of raw, cooked, and encapsulated placenta and its effects on the postpartum woman.

Gender Diversity in the Psychiatric Workforce: It's Still a (White) Man's World in Psychiatry.

Academic psychiatry has slightly higher rates of women in the upper ranks and leadership positions than academic medicine as a whole but women continue to be seriously underrepresented. Psychiatry departments should take specific steps to address barriers for women in psychiatry including harassment and discrimination, Imposter Syndrome, lack of mentorship and sponsorship, work-life integration issues, and overinvolvement in nonpromotion generating activities. Addressing these barriers within academic psychiatry will improve the environment for all minorities.

Key Findings from Mental Health Research During the Menopause Transition for Racially and Ethnically Minoritized Women Living in the United States: A Scoping Review.

Background: Racially and ethnically minoritized (REM) women experience social and structural factors that may affect their response to mental health treatment and menopausal symptoms during the menopause transition (MT). This scoping review on mental health during the MT for REM women in the United States was conducted to characterize factors associated with mental health challenges. Materials and Methods: Five databases were searched. Articles were included if focused on MT in REM women in the United States and its territories with specific mental illnesses and published in English from 2005 to 2021. Titles and abstracts and full text were screened. Screening and data collection were completed in duplicate by two reviewers in Covidence. Results: Sixty-five articles were included and indicate that REM women experience a disproportionate burden of depressive symptoms during the MT. Less evidence is reported about anxiety, Post-Traumatic Stress Disorder, psychosis, schizophrenia, and other mental illnesses. The risk factors associated with mental illness during MT are social, structural, and biological. Treatment response to therapeutic interventions is often underpowered to explain REM differences. Conclusion: Depression during the MT is associated with negative outcomes that may impact REM women differentially. Incorporating theoretical frameworks (e.g., intersectionality, weathering) into mental health research will reduce the likelihood that scientists mislabel race as the cause of these inequities, when racism and intersecting systems of oppression are the root causes of differential expression of mental illness among REM women during the MT. There is a need for interdisciplinary research to advance the mental health of REM women.

Postpartum Depression: A Clinical Review of Impact and Current Treatment Solutions.

Depression during the first year postpartum (postpartum depression) impacts millions of women and their families worldwide. In this narrative review, we provide a summary of postpartum depression, examining the etiology and consequences, pharmacological and psychological treatments, and potential mechanisms of change and current barriers to care. Psychological treatments are effective and preferred by many perinatal patients over medications, but they often remain inaccessible. Key potential mechanisms underlying their effectiveness include treatment variables (e.g., dosage and therapeutic alliance) and patient behaviors (e.g., activation and avoidance and emotional regulation). Among pharmacological treatments, the selective serotonin reuptake inhibitor (SSRI) sertraline is generally the first-line antidepressant medication recommended to women in the postpartum period due to its minimal passage into breastmilk and the corresponding decades of safety data. Importantly, most antidepressant drugs are considered compatible with breastfeeding. Neurosteroids are emerging as an effective treatment for postpartum depression, although currently this treatment is not widely available. Barriers to widespread access to treatment include those that are systematic (e.g., lack of specialist providers), provider-driven (e.g., lack of flexibility in treatment delivery), and patient-driven (e.g., stigma and lack of time for treatment engagement). We propose virtual care, task-sharing to non-specialist treatment providers, and collaborative care models as potential solutions to enhance the reach and scalability of effective treatments to address the growing burden of postpartum depression worldwide and its negative impact on families and society.

Pharmacogenomic Characterization of Childbearing-Aged Individuals With Mood Disorders in a Tertiary Care Perinatal Mental Health Clinic.

Objective: The effectiveness of antidepressant treatment for mood disorders is often limited by either a poor response or the emergence of adverse effects. These complications often necessitate multiple drug trials. This clinical challenge intensifies during pregnancy, when medications must be selected to improve the likelihood of response and optimize reproductive outcomes. We determined the distribution of common pharmacogenetic variants, metabolizer phenotypes, past medication responses, and side effects in childbearing-aged individuals seeking treatment in a tertiary care perinatal mental health clinic.Methods: Sixty treatment-seeking women (based on sex at birth) with DSM-5- defined bipolar disorder (n = 28) or major depressive disorder (n = 32) provided DNA samples and completed psychiatric diagnostic and severity assessments between April 2014 and December 2017. Samples were genotyped for single-nucleotide variants in drug metabolizing enzyme genes of commonly prescribed antidepressants (cytochrome P450 [CYP] 1A2, 2B6, 2C9, 2C19, 2D6, 3A4, and 3A5), and the frequency of normative metabolizer status was compared to reference populations data from Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. The Antidepressant Treatment History Form was used to record historic medication trials and side effects.Results: A significantly greater proportion of extensive metabolizers for CYP2B6 was observed in the study population when compared to CPIC population frequency databases in Caucasians (0.64 vs 0.43 [95% CI: 0.49-0.76]; P value = .006) and African Americans (0.71 vs 0.33 [95% CI: 0.29-0.96]; P value = .045). No significant association was found between metabolizer phenotype and the likelihood of a medication side effect.Conclusion: Pharmacogenomic testing may have value for personalized prescribing in individuals capable of or considering pregnancy.

Optimization of the Mood Disorder Questionnaire in identification of perinatal bipolar disorder.

BACKGROUND: The recognition of bipolar disorder during the perinatal period is often challenging because birthing people most commonly present in a depressive episode. The phenotypic expression of episodes of bipolar depression is difficult to differentiate from major depressive disorder and can lead to misdiagnosis and inappropriate treatment. The Mood Disorder Questionnaire is a readily available screening tool for bipolar disorder that has been validated in previous studies for use in the general and perinatal populations. However, the discriminatory capacity of the Mood Disorder Questionnaire for perinatal people who screen positive for depression in nonpsychiatric settings is still unclear. OBJECTIVE: This study aimed to evaluate the discriminatory capacity of the Mood Disorder Questionnaire to identify bipolar disorder in perinatal people who screen positive for depression on the Patient Health Questionnaire-9. STUDY DESIGN: This retrospective cohort study included individuals enrolled in the Collaborative Care Model for Perinatal Depression Support Services, a collaborative care program for perinatal mental health services implemented in a quaternary care setting, from January 2017 to April 2021. All individuals completed the Mood Disorder Questionnaire and psychiatric evaluation by a licensed clinical social worker. Clinical and sociodemographic characteristics were compared between those with and without a clinical diagnosis of bipolar disorder using bivariable analyses. The discriminatory capacity and test characteristics of the Mood Disorder Questionnaire were assessed at each score cutoff using the gold standard of a psychiatric clinical evaluation for comparison. RESULTS: From January 2017 to April 2021, 1510 birthing people were enrolled in the Collaborative Care Model for Perinatal Depression Support Services and included in this study. Among this group, 62 (4.1%) were diagnosed with bipolar disorder by psychiatric clinical evaluation using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnostic criteria. A score of ≥7 on question 1 is often used in the general population to identify bipolar disorder, which has a 60% sensitivity and 88% specificity in our perinatal sample with an area under the receiver operating characteristic curve of 0.74 (95% confidence interval, 0.72-0.76). Lowering the threshold to ≥4 improves sensitivity to 81% and the discriminatory capacity to an area under the receiver operating characteristic curve of 0.75 (95% confidence interval, 0.70-0.80), at the expense of a reduction in specificity to 69%. CONCLUSION: The administration of the Mood Disorder Questionnaire in the perinatal period can help to identify which individuals who have screened positive for depression on the Patient Health Questionnaire-9 are at risk of a bipolar or unipolar disorder. In this context, lowering the Mood Disorder Questionnaire score threshold from that used in the nonperinatal population down to 4 improves test characteristics and reduces the risk of a missed diagnosis of bipolar disorder.

Gender Diversity in the Psychiatric Workforce: It's Still a (White) Man's World in Psychiatry.

Academic psychiatry has slightly higher rates of women in the upper ranks and leadership positions than academic medicine as a whole but women continue to be seriously underrepresented. Psychiatry departments should take specific steps to address barriers for women in psychiatry including harassment and discrimination, Imposter Syndrome, lack of mentorship and sponsorship, work-life integration issues, and overinvolvement in nonpromotion generating activities. Addressing these barriers within academic psychiatry will improve the environment for all minorities.

Perinatal use of lurasidone for the treatment of bipolar disorder.

Atypical antipsychotics are commonly prescribed for the treatment of severe mental illnesses during pregnancy. Evidence regarding the impact of physiologic changes during pregnancy on the concentration of atypical antipsychotics is limited, specifically in the case of lurasidone. Data to guide dosing in pregnancy that maximizes efficacy and minimizes adverse effects are lacking. This case report presents perinatal changes in the concentration of lurasidone and the implications for Bipolar Disorder (BD) illness course in a primiparous woman. Monitoring of lurasidone serum concentrations and recurrence of BD symptoms after the second trimester of pregnancy until the third postpartum month was completed. Lurasidone serum concentrations ranged from 0 to 4.7 ng/mL during pregnancy and increased to 10-12 ng/mL postpartum. The subject presented with worsening anxiety and depressive symptoms during the second trimester of pregnancy which resulted in a 40 mg daily dose increase during the second half of her pregnancy. Despite the decrease in lurasidone to the preconception dose post-delivery, the concentrations were higher postpartum compared to pregnancy. The decrease in lurasidone serum concentrations during pregnancy may increase the risk of worsening BD symptoms and suggests the need for determination of whether therapeutic monitoring and dose titration during pregnancy decreases illness exacerbation. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Lithium Pharmacokinetics in the Perinatal Patient With Bipolar Disorder.

The pharmacokinetics of lithium, the gold standard for the treatment of bipolar disorder, are well described in nonpregnant patients. Because lithium is commonly prescribed to women of childbearing age, more data are essential to characterize lithium pharmacokinetics during the perinatal period. Lithium is primarily eliminated by the kidney. As a result, shifts in lithium elimination clearance parallel pregnancy-related changes in glomerular filtration rate. Lithium's narrow therapeutic window increases the risk for therapeutic failure and toxicity when lithium elimination clearance is altered. To characterize the pharmacokinetics of lithium in pregnancy and postpartum, 3 women treated with lithium for bipolar disorder completed serial blood sampling protocols during each trimester of pregnancy and at least once postpartum. The trajectory of lithium elimination clearance, creatinine clearance, and serum lithium concentrations were determined. Manic, depressive, and anxiety symptoms were also assessed at each study visit. Compared to the nonpregnant state, lithium elimination clearance increased an average of 63.5% by the third trimester. Lithium elimination clearance was inversely related to changes in serum lithium concentration. Mood symptoms worsened with declines in serum lithium concentration. Lithium elimination clearance returned to baseline at 4 to 9 weeks postpartum. To maintain lithium effectiveness during pregnancy and prevent toxicity postpartum, lithium therapeutic drug monitoring and dose adjustments are warranted.

Perspectives on Mental Illness Stigma Among African Immigrant Pregnant and Post-Partum Women in an Urban Setting: A Brief Report.

Purpose: This study assessed the perspectives of pregnant and postpartum African immigrant women on mental illness. Methods: We conducted a focus group session (n=14) among pregnant and postpartum African immigrant women in June 2020. We used an inductive driven thematic analysis to identify themes related to mental health stigma. Results: Five core themes emerged: conceptualization of mental health, community stigmatizing attitudes, biopsychosocial stressors, management of mental health, and methods to reduce stigma. Conclusion: Understanding the perspectives of pregnant African immigrant women at the intersection of their race, ethnicity, gender, and migration are necessary to improve engagement with mental health services.

Associations Between Implementation of the Collaborative Care Model and Disparities in Perinatal Depression Care.

OBJECTIVE: To evaluate whether perinatal collaborative care model implementation was associated with a reduction in racial disparities in depression care. METHODS: This retrospective cohort study included pregnant and postpartum people who self-identified as either Black or White, and received prenatal care at academic faculty offices affiliated with an urban quaternary medical center. Individuals were divided into two cohorts to reflect the epochs of implementation. The primary outcome was the frequency of depression screening. The secondary outcome was the frequency of provision of a treatment recommendation for those with a positive depression screen. Antenatal and postpartum care were analyzed separately. A propensity score was used in multivariable models to control for confounders chosen a priori across implementation epoch. Interaction terms were created between race and implementation epoch to identify whether effect modification was present. Subgroup analyses were performed for outcomes with significant race-by-epoch interaction terms. RESULTS: Of the 4,710 individuals included in these analyses, 4,135 (87.8%) self-identified as White and 575 (12.2%) self-identified as Black. Before implementation, Black individuals were more likely to receive screening (adjusted odds ratio [aOR] 2.44) but less likely to have a treatment recommended when a positive screen was identified (aOR 0.05). In multivariable models, race-by-epoch interaction terms were significant for both antenatal screening (P<.001) and antenatal treatment recommendation (P=.045), demonstrating that implementation of the perinatal collaborative care model was associated with reductions in extant racial disparities. After implementation, there were no significant differences by race (referent=White) in screening for antenatal depression (aOR 1.22, 95% CI 0.89-1.68) or treatment recommendations for those who screened positive (aOR 0.64, 95% CI 0.27-1.53). Race-by-epoch interaction terms were not significant in multivariable models for either postpartum screening or treatment recommendation. CONCLUSION: Implementation of the perinatal collaborative care model is associated with a mitigation of racial disparities in antenatal depression care and may be an equity-promoting intervention for maternal health.

Medical Mistrust in Perinatal Mental Health.

ABSTRACT: Despite the advancement of telemedicine and recent innovations in treatment, minoritized women continue to bear a disproportionate burden of pregnancy-related psychiatric conditions and complications, which the pandemic has further exacerbated. Research demonstrates that medical mistrust and systemic racism play central roles in the underutilization of services by racially and ethnically diverse women during pregnancy and postpartum. To effectively address these disparities, it is imperative to understand the drivers of medical mistrust in perinatal health care systems. This Perspectives article describes the historical context of medical mistrust in psychiatric and obstetric health systems and offers solutions to mitigate mistrust and the impact of systemic racism on perinatal care.

A comparison of symptoms of bipolar and unipolar depression in postpartum women.

BACKGROUND: Distinguishing postpartum women with bipolar from unipolar depression remains challenging, particularly in obstetrical and primary care settings. The post-birth period carries the highest lifetime risk for the onset or recurrence of Bipolar Disorder (BD). Characterization of differences between unipolar and bipolar depression symptom presentation and severity is critical to differentiate the two disorders. METHODS: We performed a secondary analysis of a study of 10,000 women screened by phone with the Edinburgh Postnatal Depression Scale at 4-6 weeks post-birth. Screen-positive mothers completed the Structured Clinical Interview for DSM-4 and those diagnosed with BD and unipolar Major Depressive Disorder (UD) were included. Depressive symptoms were assessed with the 29-item Structured Interview Guide for the Hamilton Rating Scale for Depression (SIGH-ADS). RESULTS: The sample consisted of 728 women with UD and 272 women with BD. Women with BD had significantly elevated levels of depression severity due to the higher scores on 8 of the 29 SIGH-ADS symptoms. Compared to UD, women with BD had significantly higher rates of comorbid anxiety disorders and were twice as likely to report sexual and/or physical abuse. LIMITATIONS: Only women who screened positive for depression were included in this analysis. Postpartum women with unstable living situations, who were hospitalized or did not respond to contact attempts did not contribute data. CONCLUSIONS: Severity of specific symptom constellations may be a useful guide for interviewing postpartum depressed women along with the presence of anxiety disorder comorbidity and physical and/or sexual abuse.