Barriers to care and treatment experiences among individuals with postpartum psychosis.

PURPOSE: Postpartum psychosis (PP) is a severe psychiatric disorder affecting 1-2 per 1,000 deliveries. Prompt access to healthcare and timely initiation of treatment are crucial to minimizing harm and improving outcomes. This analysis seeks to fill gaps in knowledge surrounding barriers to care and treatment experiences among this population. METHODS: Participants were individuals with histories of PP who enrolled in the Massachusetts General Hospital Postpartum Psychosis Project (MGHP3). The MGHP3 Healthcare Access Survey, a cross-sectional questionnaire, assesses barriers to care, treatment-seeking behaviors, and experiences with treatment. Descriptive statistics were utilized to describe sample characteristics. RESULTS: 139 participants provided 146 episode-specific survey responses. Lack of available services was cited as the greatest barrier to care for PP. Among those who sought treatment, obstetric providers (34.5%) and emergency medical professionals (29.4%) were the most common initial points of contact. 82.2% of the respondents went to an emergency room or crisis center during their episode(s). Most (61.8%) reported being given insufficient information to manage their PP. Approximately half of participants were hospitalized (55.5%), the majority of whom had no access to their infant during hospitalization (70.4%). Of those breastfeeding or pumping at admission, 31.3% were not given access to a breast pump. 44.4% dealt with delivery-related medical issues during their hospitalization. CONCLUSION: This report is the first of its kind to assess key public health domains among individuals with PP. Findings point to several directions for future research and clinical practice to improve treatment timeliness and quality, potentially improving long-term outcomes related to this serious illness.

Risk of Major Malformations Following First-Trimester Exposure to Olanzapine: Preliminary Data From the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications.

PURPOSE/BACKGROUND: Since its US Food and Drug Administration approval in 1996, olanzapine has been one of the most commonly prescribed atypical antipsychotics, making a better understanding of its reproductive safety profile critical. The goal of the current analysis was to determine the risk of major malformations among infants exposed to olanzapine during pregnancy compared with a group of nonexposed infants. METHODS/PROCEDURES: The National Pregnancy Registry for Psychiatric Medications is a prospective pharmacovigilance program in which pregnant women are enrolled and interviewed during pregnancy and the postpartum period. Labor and delivery and pediatric medical records were screened for evidence of major malformations followed by adjudication by a dysmorphologist blinded to medication exposure. Infants with first-trimester exposure to olanzapine were compared with controls without second-generation antipsychotic exposure. FINDINGS/RESULTS: As of April 18, 2022, 2619 women have enrolled in the study. At the time of data extraction, 49 olanzapine-exposed infants and 1156 infants in the comparison group were eligible for these analyses. There were no major malformations associated with olanzapine exposure in the first trimester. The absolute risk for major malformations in the exposure group was 0.00% (95% confidence interval, 0.00-7.25) for olanzapine compared with 1.64% (95% confidence interval, 0.99-2.55) in the control group. IMPLICATIONS/CONCLUSIONS: In this prospective cohort, no major malformations were associated with olanzapine exposure during the first trimester. Although these data are preliminary and cannot rule out more modest effects, they are nonetheless important, adding to the growing reproductive safety data for olanzapine.

Risk of Major Malformations in Infants After First-Trimester Exposure to Stimulants: Results From the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications.

PURPOSE/BACKGROUND: The prevalence of attention-deficit/hyperactivity disorder in adult females is 3% to 4%. Attention-deficit/hyperactivity disorder is highly comorbid with other psychiatric disorders such as mood, anxiety, and substance use disorders. For reproductive-aged women, the treatment of attention-deficit/hyperactivity disorder with stimulant medications may be considered during pregnancy or breastfeeding, although historically, data are lacking to inform these decisions. The aim of this investigation was to determine the risk of major malformations in infants after first-trimester prescription stimulant exposure in a small but rigorously characterized sample. METHODS/PROCEDURES: The Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications systematically ascertains information from pregnant females including demographic information, medical and psychiatric history, use of prescription medications, and other information relevant to fetal outcomes. Participants provide verbal informed consent and are interviewed twice during gestation and again at approximately 3 months postpartum. The primary outcome of interest is the presence of a major malformation identified within 6 months after birth. Redacted cases of major malformations are reviewed by a dysmorphologist blinded to medication exposure. FINDINGS/RESULTS: A total of N = 1988 women were eligible for this analysis, including the following exposures: n = 173 to mixed amphetamine salts; n = 40 to lisdexamfetamine; n = 45 to methylphenidate; n = 3 to dexmethylphenidate; and n = 1755 controls. The odds ratio of a major malformation among infants after first-trimester exposure to any stimulant was 0.39 (95% confidence interval, 0.09-1.61) compared with controls. There were no major malformations observed in infants exposed to lisdexamfetamine, methylphenidate, or dexmethylphenidate. IMPLICATIONS/CONCLUSIONS: Although preliminary, this analysis from an ongoing pregnancy registry provides reassurance that these stimulants do not appear to have major teratogenic effects. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01246765 .

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.

Risk of major malformations in infants after first-trimester exposure to benzodiazepines: Results from the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications.

BACKGROUND: Perinatal anxiety affects 20% of women, and untreated maternal mental illness can cause deleterious effects for women and their children. Benzodiazepines are commonly used to treat anxiety disorders. The reported risk of congenital malformations after in utero benzodiazepine exposure has been inconsistent. METHODS: The Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications prospectively enrolls pregnant women with psychiatric illness who take one or more psychiatric medications. Participants are interviewed twice during pregnancy and at 12 weeks postpartum. Women taking any benzodiazepine during the first trimester of pregnancy were compared with a group of women taking psychiatric medication(s) other than benzodiazepines during pregnancy. RESULTS: A total of 1053 women were eligible for this analysis; N = 151 women who had taken a benzodiazepine during the first trimester, and the comparison group was N = 902 women. There were 5 (3.21%) major malformations in the exposure group and 32 (3.46%) in the comparison group (odds ratio 0.92; 95% confidence interval 0.35-2.41). CONCLUSION: This ongoing pregnancy registry offers reassurance that benzodiazepines do not appear to have major teratogenic effects. The precision of relative risk estimate will improve as the number of participants increases. This and other pregnancy registries will better inform the reproductive safety of benzodiazepines.

Neurobehavioral follow-up of children exposed to selective serotonin reuptake inhibitors in utero.

BACKGROUND: Systematic data regarding long-term neurobehavioral effects of maternal antidepressant use during pregnancy are sparse. The aim of this study was to evaluate the impact of gestational exposure to antidepressants on later neurodevelopmental function. METHODS: This study describes a cohort of mother-child dyads (44 mothers, 54 children) in which maternal depressive symptoms and medication exposures were prospectively collected across pregnancy and the postpartum period. Children age 6 to 17 were assessed using validated instruments across domains of childhood behavior and executive memory and functioning. RESULTS: No associations were found between maternal use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy and atypical neurodevelopment of children. Borderline clinical or clinical ranges of internalizing symptoms were associated with exposure to a higher maternal depressive symptom burden during pregnancy compared with those in the normal range. Compared with age- and sex-matched controls, the SSRI-exposed group showed superior performance on executive function tasks; findings did not demonstrate elevated risk for abnormal neurodevelopment in children age 6 to 17 exposed to SSRIs in utero. Deviations from the norm were instead associated with higher in utero exposure to maternal depression burden. CONCLUSIONS: This study highlights the need for rigorous studies of long-term outcomes after fetal antidepressant exposure.

Body dissatisfaction and disordered eating in the perinatal period: an underrecognized high-risk timeframe and the opportunity to intervene.

The normal physical changes associated with pregnancy may increase the risk of body dissatisfaction, which is associated with negative mental health outcomes including depression and disordered eating. The purpose of this study was to explore body image and eating concerns among a sample of participants in pregnancy and postpartum and to assess interest and suggestions for a relevant intervention. This was a cross-sectional survey study requiring 10-15 min to complete. Individuals were eligible to participate in the study if they were pregnant or within 1 year postpartum, between the ages of 18 and 45, able to read and write in English, and provided online informed consent. The survey included measures and open-text questions to explore body image, eating behaviors, and related concerns in the perinatal period and to inform the development of an intervention. There were 161 participants, and over 50% were dissatisfied with their body image; 52% were among pregnant participants and 56.2% of postpartum participants. Approximately 80% reported that they would have appreciated the opportunity to participate in a program focused on body acceptance or expectations of body changes in pregnancy and postpartum. We identified intervention preferences as well as commonly reported themes regarding experiences of body image and eating concerns in pregnancy and postpartum. Body dissatisfaction and eating concerns are prevalent issues in pregnancy and postpartum, and our findings underscore an opportunity to tailor an intervention relevant to body image and disordered eating for the perinatal population.

Pregnancy outcomes after first-trimester exposure to buspirone: prospective longitudinal outcomes from the MGH National Pregnancy Registry for Psychiatric Medications.

Buspirone is commonly used to treat anxiety disorders among reproductive-aged women. To date, the reproductive safety of buspirone in humans has been particularly sparse. We sought to provide preliminary data from the Massachusetts General Hospital National Pregnancy Registry for Psychiatric Medications (NPRPM) on the risk of major malformations after first-trimester buspirone exposure. The NPRPM enrolls pregnant women with psychiatric disorders to prospectively assess for major congenital malformations after in utero exposure to psychotropics. Women are interviewed twice during pregnancy and once at 12 weeks postpartum. Data regarding women who took buspirone during the first trimester were extracted from the NPRPM database. Data were assessed as a rigorously ascertained case series to determine the incidence of major malformations among those exposed to buspirone. The primary outcome was obtained by maternal postpartum interview and medical record review. As of January 6, 2022, N = 97 women enrolled in the registry took buspirone during their first trimester. Of these women, 68 were evaluable and eligible for this analysis. Four women had twins, resulting in 72 infants. Among this sample, there were no malformations present. These preliminary data represent the only prospectively ascertained sample of pregnancy outcomes after first-trimester buspirone exposure. Albeit a small sample, no major malformations were observed in this cohort. The rigorous prospective ascertainment of outcomes is a strength of this study. Future analyses are planned that will include larger numbers of women with exposures to buspirone and comparison with control groups matched for demographic and diagnostic variables.

Efficacy and safety of esketamine nasal spray by sex in patients with treatment-resistant depression: findings from short-term randomized, controlled trials.

The objective of this analysis was to determine if there are sex differences with esketamine for treatment-resistant depression (TRD). Post hoc analyses of three randomized, controlled studies of esketamine in patients with TRD (TRANSFORM-1, TRANSFORM-2 [18-64 years], TRANSFORM-3 [≥ 65 years]) were performed. In each 4-week study, adults with TRD were randomized to esketamine or placebo nasal spray, each with a newly initiated oral antidepressant. Change from baseline to day 28 in Montgomery-Åsberg Depression Rating Scale (MADRS) total score was assessed by sex in pooled data from TRANSFORM-1/TRANSFORM-2 and separately in data from TRANSFORM-3 using a mixed-effects model for repeated measures. Use of hormonal therapy was assessed in all women, and menopausal status was assessed in women in TRANSFORM-1/TRANSFORM-2. Altogether, 702 adults (464 women) received ≥ 1 dose of intranasal study drug and antidepressant. Mean MADRS total score (SD) decreased from baseline to day 28, more so among patients treated with esketamine/antidepressant vs. antidepressant/placebo in both women and men: TRANSFORM-1/TRANSFORM-2 women-esketamine/antidepressant -20.3 (13.19) vs. antidepressant/placebo -15.8 (14.67), men-esketamine/antidepressant -18.3 (14.08) vs. antidepressant/placebo -16.0 (14.30); TRANSFORM-3 women-esketamine/antidepressant -9.9 (13.34) vs. antidepressant/placebo -6.9 (9.65), men-esketamine/antidepressant -10.3 (11.96) vs. antidepressant/placebo -5.5 (7.64). There was no significant sex effect or treatment-by-sex interaction (p > 0.35). The most common adverse events in esketamine-treated patients were nausea, dissociation, dizziness, and vertigo, each reported at a rate higher in women than men. The analyses support antidepressant efficacy and overall safety of esketamine nasal spray are similar between women and men with TRD. The TRANSFORM studies are registered at clinicaltrials.gov (identifiers: NCT02417064 (first posted 15 April 2015; last updated 4 May 2020), NCT02418585 (first posted 16 April 2015; last updated 2 June 2020), and NCT02422186 (first posted 21 April 2015; last updated 29 September 2021)).

Breastfeeding practices among women taking second-generation antipsychotics: findings from the National Pregnancy Registry for Atypical Antipsychotics.

The purpose of this study is to examine initiation rates of breastfeeding and other breastfeeding outcomes among women taking second generation antipsychotics (SGAs). Participants were enrolled in the National Pregnancy Registry for Atypical Antipsychotics; an ongoing prospective cohort study enrolling women age 18-45 years who are exposed and unexposed to SGAs during pregnancy. A 3-month postpartum interview collects information regarding breastfeeding behaviors. Specifically, women are asked the following questions about ever breastfeeding, still breastfeeding at 3 months postpartum, and whether women are breastfeeding exclusively, bottle-feeding exclusively, or breast and bottle feeding. Descriptive statistics were used to summarize demographic variables and breastfeeding practices. Rates of breastfeeding initiation and continuation were higher among participants who did not use SGAs. Among women not on SGAs, 88.2% of women reported "ever breastfeeding" compared to 59.3% of women on an SGA. At 3 months postpartum, 47% of women on a non-SGA were exclusively breastfeeding compared to 23% of women on an SGA. While the majority of women on an SGA initiated breastfeeding, breastfeeding rates were considerably lower than for women who were not on a SGA. More research is needed on the safety of lactation and use of combinations of psychotropics for women in pregnancy and postpartum.

Correction: Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD).

Supplementary Figure 1 and Supplementary Tables 1-4 have been re-uploaded so as to reflect the versions supplied during proofs stage. The publisher apologizes for the error in versioning. The HTML version of the paper has been updated.

Double-blind, placebo-controlled, dose-ranging trial of intravenous ketamine as adjunctive therapy in treatment-resistant depression (TRD).

Numerous placebo-controlled studies have demonstrated the ability of ketamine, an NMDA receptor antagonist, to induce rapid (within hours), transient antidepressant effects when administered intravenously (IV) at subanesthetic doses (0.5 mg/kg over 40 min). However, the optimal antidepressant dose remains unknown. We aimed to compare to active placebo the rapid acting antidepressant properties of a broad range of subanesthetic doses of IV ketamine among outpatients with treatment-resistant depression (TRD). A range of IV ketamine doses were compared to active placebo in the treatment of adult TRD over a 3-day period following a single infusion over 40 min. This was an outpatient study conducted across six US academic sites. Outpatients were 18-70 years old with TRD, defined as failure to achieve a satisfactory response (e.g., less than 50% improvement of depression symptoms) to at least two adequate treatment courses during the current depressive episode. Following a washout period, 99 eligible subjects were randomly assigned to one of the five arms in a 1:1:1:1:1 fashion: a single intravenous dose of ketamine 0.1 mg/kg (n = 18), a single dose of ketamine 0.2 mg/kg (n = 20), a single dose of ketamine 0.5 mg/kg (n = 22), a single dose of ketamine 1.0 mg/kg (n = 20), and a single dose of midazolam 0.045 mg/kg (active placebo) (n = 19). The study assessments (HAM-D-6, MADRS, SDQ, PAS, CGI-S, and CGI-I) were performed at days 0, 1, 3 (endpoint), 5, 7, 14, and 30 to assess the safety and efficacy. The overall group × time interaction effect was significant for the primary outcome measure, the HAM-D-6. In post hoc pairwise comparisons controlling for multiple comparisons, standard dose (0.5 mg/kg) and high dose (1 mg/kg) of intravenous ketamine were superior to active placebo; a low dose (0.1 mg/kg) was significant only prior to adjustment (p = 0.02, p-adj = 0.14, d = -0.82 at day 1). Most of the interaction effect was due to differences at day 1, with no significant adjusted pairwise differences at day 3. This pattern generally held for secondary outcomes. The infusions of ketamine were relatively well tolerated compared to active placebo, except for greater dissociative symptoms and transient blood pressure elevations with the higher doses. Our results suggest that there is evidence for the efficacy of the 0.5 mg/kg and 1.0 mg/kg subanesthetic doses of IV ketamine and no clear or consistent evidence for clinically meaningful efficacy of lower doses of IV ketamine. Trial Registration: NCT01920555.

Postpartum depression screening: Treatment engagement, barriers to care, and change in depressive symptoms.

BACKGROUND: Postpartum depression (PPD) is a common condition associated with childbirth, yet many women do not receive the treatment they need. Despite the growing practice of PPD screening, treatment and clinical outcomes among patients identified as likely having PPD remain unclear. METHOD: Women who were systematically screened and scored ≥12 on the Edinburgh Postnatal Depression Scale (EPDS)-indicative of possible PPD-at their routine 6-week postpartum visit were eligible to participate and were contacted after 3 months for a follow-up interview and assessment. RESULTS: A total of 33 women participated in the study, out of 100 who scored ≥12 on the EPDS. Among the participants, 70% reported they received a referral to a health care provider for PPD, and nearly one-half said that they received psychotherapy and/or were prescribed a psychotropic. The 2 most commonly described barriers to treatment were perceptions of not needing or wanting help and concerns about breastfeeding while taking psychotropics. Nearly 40% of women scored ≥12 on the EPDS at the follow-up interview. CONCLUSIONS: Further systematic research on outcomes after PPD screening is needed to ensure that screening translates into meaningfully improved clinical outcomes.

Reproductive safety of aripiprazole: data from the Massachusetts General Hospital National Pregnancy Registry for Atypical Antipsychotics.

Aripiprazole has become one of the most commonly prescribed psychotropics, making a more comprehensive understanding of its reproductive safety profile a priority. The goal of the current analysis was to determine the risk of major malformations in infants exposed during the first trimester of pregnancy to aripiprazole compared to infants whose mothers had psychiatric diagnoses but did not use an atypical antipsychotic during pregnancy. The National Pregnancy Registry for Atypical Antipsychotics is a prospective pharmacovigilance program in which pregnant women are enrolled and interviewed during pregnancy and the postpartum period. Medical records are assessed to confirm presence or absence of major malformations. Pregnant women ages 18-45 with psychiatric diagnoses are enrolled. As of April 2020, N = 848 women who had delivered infants were eligible for analyses. A total of 158 women with first trimester exposure to aripiprazole were compared to 690 controls. For 163 infants born to women in the exposed group, seven major malformations were confirmed (4.29%), compared to fourteen of the 690 unexposed infants (1.99%). The unadjusted odds ratio for major malformations between aripiprazole-exposed and unexposed infants was 2.21 (95% confidence interval [CI] = (0.88, 5.57) The adjusted odds ratio for major malformations was 1.35 (95% confidence interval [CI] = (0.43, 4.20). After adjustment for confounding variables, the risk of major malformations after first trimester exposure to aripiprazole was not significant compared to controls. While these results are reassuring, they are limited by relatively small numbers of participants. Future analyses with larger numbers are expected to provide more of a complete and precise reproductive safety profile regarding aripiprazole use during pregnancy. Trial registration: clinicaltrials.gov NCT01246765.

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.

Improvement of sexual functioning during treatment of MDD with adjunctive pimavanserin: A secondary analysis.

BACKGROUND: Sexual dysfunction is common among patients with major depressive disorder (MDD). In the CLARITY study, the safety and efficacy of adjunctive pimavanserin, an inverse agonist at 5-HT2A receptors, were demonstrated when added to existing treatment for MDD. This analysis provides a detailed assessment of the effects of pimavanserin on sexual function from the CLARITY study. METHODS: Patients with a diagnosis of MDD in a depressive episode, inadequate response to ongoing antidepressant therapy, and a Montgomery-Åsberg Depression Rating Scale total score >20 were randomized to pimavanserin 34 mg/day or placebo added to ongoing treatment with an immediate revision of all selective serotonin or serotonin-norepinephrine for 5 weeks (Stage 1), and nonresponders (<50% improvement from baseline in Hamilton Depression Rating Scale [HAMD-17]) were re-randomized for an additional 5 week (Stage 2). Effects of pimavanserin on the Massachusetts General Hospital Sexual Functioning Index (MGH-SFI) and HAMD-17 Item 14 (sexual interest) were examined. RESULTS: Among 203 patients (51 on pimavanserin; 152 on placebo), pimavanserin demonstrated significant improvement from baseline to Week 5 on the MGH-SFI (least square [LS]mean difference -0.634, 95% confidence interval [CI] [-0.964, -0.304]; p = .0002; effect size [ES], Cohen's d: .614). Across Stages 1 and 2, the weighted LSmean difference was -0.468 (95% CI [-0.720, -0.216]; p = .0003) for pimavanserin versus placebo. Mean changes from baseline to Week 5 for MGH-SFI Items 1, 2, 3, and 5 and HAMD Item 14 were significantly (p < .05) greater with pimavanserin versus placebo. CONCLUSIONS: Adjunctive pimavanserin improved sexual function in patients with MDD. Adding pimavanserin to ongoing treatment for MDD may be especially useful for patients experiencing sexual dysfunction.

International Society for Nutritional Psychiatry Research Practice Guidelines for Omega-3 Fatty Acids in the Treatment of Major Depressive Disorder.

Major depressive disorder (MDD) is a complex mental illness with unmet therapeutic needs. The antidepressant effects of ω-3 polyunsaturated fatty acids (n-3 PUFAs) have been widely reported. The subcommittee of the International Society for Nutritional Psychiatry Research organized an expert panel and conducted a literature review and a Delphi process to develop a consensus-based practice guideline for clinical use of n-3 PUFAs in MDD. The guideline focuses on 5 thematic areas: general concepts, acute treatment strategy, depression recurrence monitoring and prevention, use in special populations, and potential safety issues. The key practice guidelines contend that: (1) clinicians and other practitioners are advised to conduct a clinical interview to validate clinical diagnoses, physical conditions, and measurement-based psychopathological assessments in the therapeutic settings when recommending n-3 PUFAs in depression treatment; (2) with respect to formulation and dosage, both pure eicosapentaenoic acid (EPA) or an EPA/docosahexaenoic acid (DHA) combination of a ratio higher than 2 (EPA/DHA >2) are considered effective, and the recommended dosages should be 1-2 g of net EPA daily, from either pure EPA or an EPA/DHA (>2:1) formula; (3) the quality of n-3 PUFAs may affect therapeutic activity; and (4) potential adverse effects, such as gastrointestinal and dermatological conditions, should be monitored, as well as obtaining comprehensive metabolic panels. The expert consensus panel has agreed on using n-3 PUFAs in MDD treatment for pregnant women, children, and the elderly, and prevention in high-risk populations. Personalizing the clinical application of n-3 PUFAs in subgroups of MDD with a low Omega-3 Index or high levels of inflammatory markers might be regarded as areas that deserve future research.

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.

A prenatal supplement with methylfolate for the treatment and prevention of depression in women trying to conceive and during pregnancy.

BACKGROUND: Women often seek antidepressant alternatives for major depressive disorder (MDD) in anticipation of or during pregnancy. In this preliminary study, EnBrace HR, a prenatal supplement containing methylfolate, was investigated for depressive relapse prevention and for acute treatment of MDD in women planning pregnancy or during pregnancy. METHODS: This 12-week open-label study included women with histories of MDD who were planning pregnancy or pregnant < 28 weeks. At enrollment, Group 1 participants were well (not depressed) and planned to discontinue antidepressants for pregnancy. Group 2 participants were depressed. Primary outcome variables by group included MDD relapse and depressive symptoms, verified with the Mini-International Neuropsychiatric Interview and the Montgomery-Åsberg Depression Rating Scale (MADRS), respectively. Biomarkers of inflammation and the folate cycle were collected. RESULTS: Group 1 participants (N = 11) experienced lower rates of depressive relapse (27.3% P = .005) than expected from a historical comparison group and no significant changes in MADRS scores. Group 2 participants (N = 6) experienced significant improvements in MADRS scores (P = .001), with 5 (83.3%) improving >50% and 1 improving 33.3%. One adverse event occurred, a hospitalization for depression. CONCLUSIONS: Results suggest EnBrace HR is a well-tolerated intervention with potential efficacy for prevention and treatment of perinatal depression. Larger controlled trials are necessary.

Course of major depressive disorder after pregnancy and the postpartum period.

BACKGROUND: Maternal major depressive disorder (MDD) has an adverse effect on child development and increases risk for child psychopathology. It is paramount to understand the course of maternal depression during the childhood years particularly before, during, and after pregnancy. OBJECTIVE: To follow the course of MDD in women with prior histories of depression followed during an index pregnancy. METHODS: Subjects were women with histories of MDD who had participated in prior prospective, observational studies during pregnancy. In the follow-up, participants completed a structured interview that addressed (1) the course of MDD since their index pregnancy, (2) new psychiatric diagnoses, and (3) the course of MDD and treatment across subsequent pregnancies. RESULTS: Out of 129 eligible women, 48.8% participated (N = 63) with an average/mean time of 12.9 years (SD = 1.9, 8.8-16.7) elapsed since participation in the prior pregnancy studies. Although approximately one third reported sustained remission from MDD since the pregnancy during which they had been originally followed, of the remaining two thirds of women who reported subsequent depressive episodes, almost one fifth (∼12% of the total sample) endorsed depression more than 50% of the time following their index pregnancy. A total of 6.3% of the women with previous validated diagnoses of MDD reported new diagnoses of bipolar disorder. Women reported similar treatment choices regarding the use of antidepressants during pregnancies subsequent to the one followed in the previous study. CONCLUSION: Women with MDD experienced high rates of recurrent depression across the childbearing years. This represents a critical variable for clinical care and research.