Long-Term Safety and Efficacy of Initial and Repeat Treatment Courses With Zuranolone in Adult Patients With Major Depressive Disorder: Interim Results From the Open-Label, Phase 3 SHORELINE Study.

Objective: Zuranolone is a positive allosteric modulator of both synaptic and extrasynaptic γ-aminobutyric acid (GABA) type A receptors and a neuroactive steroid approved in the United States as an oral, once-daily, 14-day treatment course for adults with postpartum depression and under investigation for adults with major depressive disorder (MDD). Interim results from the open-label, longitudinal, phase 3 SHORELINE Study (NCT03864614) that evaluated the long-term safety and efficacy of zuranolone in adults with MDD are reported.Methods: This interim report includes patients who were enrolled and had the opportunity to be on study for up to 1 year between February 2019 and September 2021. Adults aged 18-75 years with MDD diagnosed per DSM-5 criteria and a 17-item Hamilton Rating Scale for Depression (HAMD-17) total score ≥ 20 received an initial 30-mg or 50-mg 14-day zuranolone course. HAMD-17 responders (≥ 50% reduction from baseline) at Day (D)15 of the initial treatment period were allowed to continue in the study beyond D28 and were followed up for ≤ 1 year, during which repeat treatment courses were permitted. The primary endpoint was safety and tolerability of the initial and repeat treatment courses through 1 year. Secondary endpoints included change from baseline (CFB) in HAMD-17 total score and need for repeat treatment course(s).Results: As of September 2021, among patients in the 30-mg (n = 725) and 50-mg (n = 199) Cohorts who received a zuranolone dose, 493 (68.0%) and 137 (68.8%), respectively, reported a treatment-emergent adverse event (TEAE); most patients who experienced TEAEs reported mild/moderate events (30-mg Cohort, 90.9% [448/493]; 50-mg Cohort, 85.4% [117/137]). Mean (standard deviation) CFB HAMD-17 total score at D15 of the initial treatment period was -15.2 (7.1) and -16.0 (6.0) for the 30-mg and 50-mg Cohorts, respectively; similar improvements were observed after repeat treatment courses. The proportion of patients who received only 1 treatment course during their time on study was 42.9% (210/489) in the 30-mg Cohort and 54.8% (80/146) in the 50-mg Cohort; 57.1% (279/489) and 45.2% (66/146) patients, respectively, received 2-5 total treatment courses. The majority of patients who initially responded to zuranolone received ≤ 2 total treatment courses (30-mg Cohort, 68.5% [335/489]; 50-mg Cohort, 79.5% [116/146]).Conclusions: Of patients who experienced TEAEs, most reported mild or moderately severe events, and responders to zuranolone experienced improvements in depressive symptoms with initial and repeat treatment courses.Trial Registration: ClinicalTrials.gov identifier: NCT03864614.

Working with Survivors of Sex Trafficking: Mental Health Implications.

Human trafficking is one of the largest criminal enterprises in the world, generating an estimated $150 billion in illegal profits annually. Sex trafficking is the most common form of human trafficking, and survivors experience significant physical, emotional, and sexual trauma that places them at increased risk of poor health outcomes. As sex trafficking continues to disproportionately impact the physical and mental health of individuals belonging to marginalized groups, a multidisciplinary approach to combat trafficking will require collaboration between health services, law enforcement, and social services. Therefore, medical professionals should be familiar with screening protocols for trafficking and evidence based, trauma-informed mental health treatment interventions.

Does Symptom-Onset Treatment With Sertraline Improve Functional Impairment for Individuals With Premenstrual Dysphoric Disorder?: A Randomized Controlled Trial.

PURPOSE/BACKGROUND: Daily treatment with sertraline improves functional impairment among individuals with premenstrual dysphoric disorder (PMDD). We do not know whether treatment initiated at symptom onset also improves functional impairment. METHODS/PROCEDURES: This 3-site, double blind, randomized, clinical trial compared sertraline (25-100 mg) to similar appearing placebo, both administered at symptom onset, for reduction of PMDD symptoms. Ninety participants were allocated to sertraline and 94 participants to placebo. Functional outcomes from the Daily Ratings of the Severity of Problems included (1) reduced productivity or efficiency at work, school, home, or daily routine; (2) interference with hobbies or social activities; and (3) interference with relationships. Items were measured from 1 (no interference) to 6 (extreme interference) and averaged for the final 5 luteal phase days. This secondary analysis examined whether improvement in functional domains was greater for those allocated to sertraline compared with placebo. Second, we used causal mediation analyses to explore whether specific PMDD symptoms mediated functional improvement. RESULTS/FINDINGS: Only relationship functioning improved significantly with active treatment between baseline and the end of the second cycle (active group mean [SD] change, -1.39 [1.38]; placebo group mean change, -0.76 [1.20]; ß = -0.40; SE, 0.15; P = 0.009). The total effect of treatment on interference was -0.37 (95% confidence interval [CI], -0.66 to -0.09; P = 0.011). Given the nonsignificant direct effect (0.11; 95% CI, -0.07 to 0.29; P = 0.24) and significant indirect effect (-0.48; 95% CI, -0.71 to -0.24; P < 0.001), amelioration of anger/irritability likely mediated reductions in relationship interference. IMPLICATIONS/CONCLUSIONS: That anger/irritability mediates impairments in relationship functioning has face validity but should be replicated in other data sets. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00536198 .

Multidisciplinary Management of Menopause: Symposium Proceedings.

This proceeding summarizes a symposium on multidisciplinary management of menopause held on July 30, 2021 as part of the Health of Women 2021 conference. The workshop featured presentations by national experts who provided insights into multidisciplinary approaches to the management of menopause, vasomotor symptoms and genitourinary syndrome of menopause, bone health (including osteoporosis, muscular strength, and mobility), as well as sexual and psychological health during menopause. In this study, we highlight the major points of each presentation and the resultant discussion.

Evaluation of an Electronic Health Record Alert to Improve Screening and Management of Cardiovascular Disease and Stroke Factors in a High-Risk Population.

OBJECTIVES: Cardiovascular disease and stroke risk factor screening and management by primary care providers (PCPs) have a significant impact on their patients' health. The objective of this study was to investigate the effectiveness of an electronic health record (EHR) cardiovascular disease and stroke risk alert in improving the ability of PCPs to manage risk factors among women and men aged 45 years and older. METHODS: PCPs at a tertiary care hospital were randomized. The intervention group received an EHR alert, which calculated the individual patient risk and provided an order set incorporating the American Heart Association and American Stroke Association guidelines, whereas the control group used the EHR in the usual manner. Multilevel analysis compared the rate of prescriptions between the intervention and control groups. RESULTS: A total of 23 PCPs were randomized: 12 in the intervention group and 11 in the control group, attending to 7190 patients between September 2016 and January 2017. None of the providers in the intervention group used the programmed order set. Intervention group providers were significantly more likely to prescribe smoking cessation medication to women than to the control group (adjusted odds ratio 2.37, 95% confidence interval 1.23-4.57). There were no statistically significant differences between the intervention and control groups in the rate of other medication prescriptions. CONCLUSIONS: As measured by prescriptions for medications, other than those for smoking cessation, the EHR alert was not shown to be successful in increasing the management of high-risk patients. Physicians receiving numerous messages in the EHR may experience alert desensitization.

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)).

Prenatal Depression Severity and Postpartum Care Utilization in a Medicaid Population.

Background: Postpartum visits are a necessary continuum of medical care for women who are diagnosed with depression during pregnancy. However, postpartum care utilization is typically lower in populations who face adverse events and it is unclear to what extent having depression during pregnancy may compromise postpartum visit follow-up. Our study examined the association between severity of prenatal depression and postpartum care utilization among women on Medicaid. Materials and Methods: Data from a university-based, nonprofit managed care organization (2008-2012) were analyzed (N = 846). Prenatal depression severity and postpartum care utilization were determined using the International Classification of Diseases, Ninth Revision (ICD-9) codes, from medical claims records. Bivariate and multivariable logistic regression was conducted. Odds ratios and 95% confidence intervals (CIs) were calculated. Results: The majority (64.2%) of women received a mild/moderate prenatal depression diagnosis and 52.5% of the total sample attended their postpartum care visit. After adjusting for confounders, we found decreased odds of postpartum care utilization among women with less severe diagnoses. Women with a mild/moderate prenatal depression diagnosis were 12% less likely to attend the postpartum care visit compared with women with a severe prenatal depression diagnosis (adjusted odds ratio = 0.88, 95% CI = 0.65-1.19). However, this finding was not statistically significant. Conclusions: Our study did not yield evidence of a statistically significant relationship between prenatal depression severity and postpartum visit attendance among a sample of Medicaid beneficiaries. Additional research is needed to assess the association between prenatal depression severity and postpartum care use to enhance continuity of services for Medicaid-insured women into the postpartum period.

Clinical Characteristics and Treatment Response to Lisdexamfetamine Dimesylate Versus Placebo in Adults With Binge Eating Disorder: Analysis by Gender and Age.

OBJECTIVE: To describe clinical characteristics and lisdexamfetamine dimesylate (LDX) treatment effects, based on gender and age, in adults diagnosed with moderate to severe binge eating disorder (BED). METHODS: Adults diagnosed with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision-defined BED of moderate to severe severity were randomized to 12 weeks of dose-optimized LDX (50 or 70 mg) or placebo in 2 studies (conducted from November 26, 2012, to September 25, 2013 [study 1] and from November 26, 2012, to September 20, 2013 [study 2]). These post hoc analyses pooled data by gender (men vs women) and age (< 40 vs ≥ 40 years) across studies; reported P values are nominal (descriptive and unadjusted). RESULTS: The pooled safety analysis and full analysis sets included 745 and 724 participants, respectively (men, n = 105 and n = 97; women, n = 640 and n = 627; < 40 years, n = 398 and n = 386; ≥ 40 years, n = 347 and n = 338). Across subgroups, most participants had a body mass index ≥ 30 kg/m² (63.0%-75.5%). The mean baseline number of binge eating days/wk was comparable across gender (4.6-4.7) and age (4.6-4.9), as was Yale-Brown Obsessive Compulsive Scale modified for Binge Eating (Y-BOCS-BE) total score (gender, 20.42-21.70; age, 21.40-21.63). Least squares mean (95% CI) treatment differences nominally favored LDX in all subgroups (all P < .001) for changes from baseline in binge eating days/wk at weeks 11-12 and in Y-BOCS-BE total score at week 12; no interactions by gender or age were reported. Consistent with the overall profile of LDX, across all subgroups LDX was associated with higher frequencies of treatment-emergent adverse events than placebo and with increases in blood pressure and pulse. CONCLUSIONS: Across gender and age, participants exhibited comparable clinical characteristics and responses to dose-optimized LDX compared with placebo. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT01718483 and NCT01718509.

Guidelines for the Evaluation and Treatment of Perimenopausal Depression: Summary and Recommendations.

There is a new appreciation of the perimenopause-defined as the early and late menopause transition stages as well as the early postmenopause-as a window of vulnerability for the development of both depressive symptoms and major depressive episodes. However, clinical recommendations on how to identify, characterize and treat clinical depression are lacking. To address this gap, an expert panel was convened to systematically review the published literature and develop guidelines on the evaluation and management of perimenopausal depression. The areas addressed included: (1) epidemiology; (2) clinical presentation; (3) therapeutic effects of antidepressants; (4) effects of hormone therapy; and (5) efficacy of other therapies (e.g., psychotherapy, exercise, and natural health products). Overall, evidence generally suggests that most midlife women who experience a major depressive episode during the perimenopause have experienced a prior episode of depression. Midlife depression presents with classic depressive symptoms commonly in combination with menopause symptoms (i.e., vasomotor symptoms, sleep disturbance), and psychosocial challenges. Menopause symptoms complicate, co-occur, and overlap with the presentation of depression. Diagnosis involves identification of menopausal stage, assessment of co-occurring psychiatric and menopause symptoms, appreciation of the psychosocial factors common in midlife, differential diagnoses, and the use of validated screening instruments. Proven therapeutic options for depression (i.e., antidepressants, psychotherapy) are the front-line treatments for perimenopausal depression. Although estrogen therapy is not approved to treat perimenopausal depression, there is evidence that it has antidepressant effects in perimenopausal women, particularly those with concomitant vasomotor symptoms. Data on estrogen plus progestin are sparse and inconclusive.

Working Together to Address Women's Health in Research and Drug Development: Summary of the 2017 Women's Health Congress Preconference Symposium.

Historically, women have been underrepresented in clinical research, requiring physicians to extrapolate medical recommendations for women from clinical research done in cohorts consisting predominantly of male participants. While government-funded clinical research has achieved gender parity in phase-3 clinical trials across many biomedical disciplines, improvements are still needed in several facets of women's health research, such as the inclusion of women in early-phase clinical trials, the inclusion of pregnant women and women with physical and intellectual disabilities, the consideration of sex as a biological variable in preclinical research, and the analysis and reporting of sex and gender differences across the full biomedical research continuum. The National Institutes of Health (NIH) Office of Research on Women's Health and the Office of Women's Health of the U.S. Food and Drug Administration (FDA) cosponsored a preconference symposium at the 25th Annual Women's Health Congress, held in Arlington, VA in April, 2017, to highlight gains made and remaining needs regarding the representation of women in clinical research, to introduce innovative procedures and technologies, and to outline revised policy for future studies. Six speakers presented information on a range of subjects related to the representation of women in clinical research and federal initiatives to advance precision medicine. Topics included the following: the return on investment from the NIH-funded Women's Health Initiative; progress in including women in clinical trials for FDA-approved drugs and products; the importance of clinical trials in pregnant women; FDA initiatives to report drug safety during pregnancy; the NIH-funded All of Us Research Program; and efforts to enhance FDA transparency and communications, including the introduction of Drug Trials Snapshots. This article summarizes the major points of the presentations and the discussions that followed.

Guidelines for the evaluation and treatment of perimenopausal depression: summary and recommendations.

There is a new appreciation of the perimenopause - defined as the early and late menopause transition stages as well as the early postmenopause - as a window of vulnerability for the development of both depressive symptoms and major depressive episodes. However, clinical recommendations on how to identify, characterize and treat clinical depression are lacking. To address this gap, an expert panel was convened to systematically review the published literature and develop guidelines on the evaluation and management of perimenopausal depression. The areas addressed included: 1) epidemiology; 2) clinical presentation; 3) therapeutic effects of antidepressants; 4) effects of hormone therapy; and 5) efficacy of other therapies (eg, psychotherapy, exercise, and natural health products). Overall, evidence generally suggests that most midlife women who experience a major depressive episode during the perimenopause have experienced a prior episode of depression. Midlife depression presents with classic depressive symptoms commonly in combination with menopause symptoms (ie, vasomotor symptoms, sleep disturbance), and psychosocial challenges. Menopause symptoms complicate, co-occur, and overlap with the presentation of depression. Diagnosis involves identification of menopausal stage, assessment of co-occurring psychiatric and menopause symptoms, appreciation of the psychosocial factors common in midlife, differential diagnoses, and the use of validated screening instruments. Proven therapeutic options for depression (ie, antidepressants, psychotherapy) are the front-line treatments for perimenopausal depression. Although estrogen therapy is not approved to treat perimenopausal depression, there is evidence that it has antidepressant effects in perimenopausal women, particularly those with concomitant vasomotor symptoms. Data on estrogen plus progestin are sparse and inconclusive.

Identifying clinical net benefit of psychotropic medication use with latent variable techniques: Evidence from Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

BACKGROUND: Poor medication adherence is common among individuals with Bipolar Disorder (BD). Understanding the sources of heterogeneity in clinical net benefit (CNB) and how it is related to psychotropic medications can provide new insight into ways to improve adherence. METHODS: Data come from the baseline assessments of the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Latent class analysis identified groups of CNB, and validity of this construct was assessed using the SF-36. Adherence was defined as taking 75% or more of medications as prescribed. Associations between CNB and adherence were tested using multiple logistic regression adjusting for sociodemographic characteristics. RESULTS: Five classes of CNB were identified: High (24%), Moderately high (12%), Moderate (26%), Moderately low (27%) and Low (12%). Adherence to psychotropic medications did not differ across classes (71% to 75%, χ2 = 3.43, p = 0.488). Medication regimens differed by class: 57% of the High CNB were taking ≤2 medications, whereas 49% of the Low CNB were taking ≥4. CNB classes had good concordance with the SF-36. LIMITATIONS: Missing data limited measures used to define CNB. Participants' perceptions of their illness and treatment were not assessed. CONCLUSIONS: This novel operationalization of CNB has construct validity as indicated by the SF-36. Although CNB and polypharmacy regimens are heterogeneous in this sample, adherence is similar across CNB. Studying adherent individuals, despite suboptimal CNB, may provide novel insights into aspects influencing adherence.

Correlates of Postpartum Visits Among Medicaid Recipients: An Analysis Using Claims Data from a Managed Care Organization.

BACKGROUND: The postpartum care visit (PPCV) plays an important role in ensuring the well-being of mother and infant. This study sought to assess correlates of PPCV attendance among women who are at high risk of nonattendance. MATERIALS AND METHODS: This study used deidentified medical claims data from Virginia Premier-a nonprofit Managed Care Organization that provides health insurance for Medicaid beneficiaries. The association between various correlates and PPCV attendance was examined using multiple logistic regression analyses. RESULTS: Of the 25,692 women in the study, more than half (50.5%) did not attend a postpartum visit. Racial/ethnic minorities and women receiving the majority of their care at hospitals, Health Departments, or Federally Qualified Health Centers were more likely to attend their postpartum visit. Women who smoked and those who did not attend prenatal care had reduced odds of postpartum visit attendance. Age, education, and delivery method were not found to be significantly associated with PPCV attendance. CONCLUSIONS: Our results highlight factors associated with attendance of PPCVs in low income populations. The continued disparity in postpartum care utilization compels additional efforts to improve access to health services across socioeconomic and demographic boundaries.

A Report of the 24th Annual Congress on Women's Health-Workshop on Transforming Women's Health: From Research to Practice.

Sex and gender are critical contributors to overall health and disease, and considering both in research informs the development of prevention strategies and treatment interventions for both men and women. The National Institutes of Health (NIH) Office of Research on Women's Health sponsored a preconference workshop on this topic at the 24th Annual Women's Health Congress, which was held in Crystal City, VA, in April 2016. The workshop featured presentations by NIH intramural and extramural scientists who presented data on a variety of topics including polycystic kidney disease, vaccine protection, depression, drug addiction, and cardiovascular disease. In this publication, we discuss the major points of each presentation and demonstrate the importance of considering sex and gender in biomedical research.

Guías para evaluación y tratamiento de depresión perimenopausica parte 2 / Guidelines for evaluation and treatment of perimenopausal depression: part2

Resumen Hay una nueva apreciación de la perimenopausia, definida como las etapas de transición temprana y tardía de la menopausia, también como la posmenopausia temprana, como una ventana de vulnerabilidad para el desarrollo de síntomas depresivos y episodios depresivos mayores. Sin embargo, las recomendaciones clínicas sobre cómo identificar, caracterizar y tratar la depresión clínica están faltando. Para abordar esta brecha, se convocó un panel de expertos para revisar sistemáticamente la literatura publicada y desarrollar lineamientos sobre la evaluación y manejo de la depresión perimenopáusica. Las áreas abordadas incluyeron: 1) epidemiología; 2) presentación clínica; 3) efectos terapéuticos de los antidepresivos; 4) efectos de la terapia hormonal; y 5) la eficacia de otras terapias (por ejemplo, psicoterapia, ejercicio y productos naturales para la salud). En general, la evidencia sugiere que la mayoría de las mujeres de mediana edad que experimentan un episodio depresivo mayor durante la perimenopausia han tenido un episodio previo de depresión. La depresión de la mediana edad se presenta con síntomas depresivos clásicos comúnmente en combinación con síntomas de la menopausia (es decir, síntomas vasomotores, trastornos del sueño) y problemas psicosociales. Los síntomas de la menopausia se complican, coexisten y se superponen con la presentación de la depresión. El diagnóstico implica la identificación de la etapa menopáusica, la evaluación de los síntomas psiquiátricos y de la menopausia (los cuales son concurrentes), apreciación de los factores psicosociales comunes en la mediana edad, diagnósticos diferenciales y el uso de pruebas de detección con instrumentos validadas. Las opciones terapéuticas probadas para la depresión (es decir, antidepresivos, psicoterapia) son la primera línea de tratamientos para la depresión perimenopáusica. Aunque la terapia con estrógenos no está aprobada para tratar la perimenopausia, existe evidencia de que tiene efectos antidepresivos en mujeres perimenopáusicas, particularmente en aquellas con síntomas vasomotores concomitantes. Los datos sobre estrógeno más progestina son escasos y no concluyentes.

Abstract There is a new appreciation of the perimenopause ­ defined as the early and late menopause transition stages as well as the early postmenopause - as a windowof vulnerability for the development of both depressive symptoms and major depressive episodes. However, clinical recommendations on how to identify, characterize and treat clinical depression are lacking. To address this gap, an expert panel was convened to systematically review the published literature and develop guidelines on the evaluation and management of perimenopausal depression. The areas addressed included: 1) epidemiology; 2) clinical presentation; 3) therapeutic effects of antidepressants; 4) effects ofhormonetherapy;and5)efficacyofothertherapies(eg,psychotherapy,exercise,andnatural health products). Overall, evidence generally suggests that most midlife women who experience a major depressive episode during the perimenopause have experienced a prior episode of depression. Midlife depression presents with classic depressive symptoms commonly in combination with menopause symptoms (ie, vasomotor symptoms, sleep disturbance), and psychosocial challenges. Menopause symptoms complicate, co-occur, and overlap with the presentation of depression. Diagnosis involves identification of menopausal stage, assessment of co-occurring psychiatric and menopause symptoms, appreciation of the psychosocial factors common in midlife, differential diagnoses, and the use of validated screening instruments. Proven therapeutic options for depression (ie, antidepressants, psychotherapy) are the front-line treatments for perimenopausal depression. Although estrogen therapy is not approved to treat perimenopausal depression, there is evidence that it has antidepressant effects in perimenopausal women particularly those with concomitant vasomotor symptoms. Data on estrogen plus progestin are sparse and inconclusive.

Consenso. Parte I Guías para evaluación y tratamiento de depresión perimenopausica: recomendaciones / Consensus. Part I Guidelines for evaluation and treatment of perimenopausal depression: recommendations

Hay una nueva apreciación de la perimenopausia, definida como las etapas de transición temprana y tardía de la menopausia, también como la posmenopausia temprana, como una ventana de vulnerabilidad para el desarrollo de síntomas depresivos y episodios depresivos mayores. Sin embargo, las recomendaciones clínicas sobre cómo identificar, caracterizar y tratar la depresión clínica están faltando. Para abordar esta brecha, se convocó un panel de expertos para revisar sistemáticamente la literatura publicada y desarrollar lineamientos sobre la evaluación y manejo de la depresión perimenopáusica. Las áreas abordadas incluyeron: 1) epidemiología; 2) presentación clínica; 3) efectos terapéuticos de los antidepresivos; 4) efectos de la terapia hormonal; y 5) la eficacia de otras terapias (por ejemplo, psicoterapia, ejercicio y productos naturales para la salud). En general, la evidencia sugiere que la mayoría de las mujeres de mediana edad que experimentan un episodio depresivo mayor durante la perimenopausia han tenido un episodio previo de depresión. La depresión de la mediana edad se presenta con síntomas depresivos clásicos comúnmente en combinación con síntomas de la menopausia (es decir, síntomas vasomotores, trastornos del sueño) y problemas psicosociales. Los síntomas de la menopausia se complican, coexisten y se superponen con la presentación de la depresión. El diagnóstico implica la identificación de la etapa menopáusica, la evaluación de los síntomas psiquiátricos y de la menopausia (los cuales son concurrentes), apreciación de los factores psicosociales comunes en la mediana edad, diagnósticos diferenciales y el uso de pruebas de detección con instrumentos validadas. Las opciones terapéuticas probadas para la depresión (es decir, antidepresivos, psicoterapia) son la primera línea de tratamientos para la depresión perimenopáusica. Aunque la terapia con estrógenos no está aprobada para tratar la perimenopausia, existe evidencia de que tiene efectos antidepresivos en mujeres perimenopáusicas, particularmente en aquellas con síntomas vasomotores concomitantes. Los datos sobre estrógeno más progestina son escasos y no concluyentes.

There is a new appreciation of the perimenopause ­ defined as the early and late menopause transition stages as well as the early postmenopause - as a windowof vulnerability for the development of both depressive symptoms and major depressive episodes. However, clinical recommendations on how to identify, characterize and treat clinical depression are lacking. To address this gap, an expert panel was convened to systematically review the published literature and develop guidelines on the evaluation and management of perimenopausal depression. The areas addressed included: 1) epidemiology; 2) clinical presentation; 3) therapeutic effects of antidepressants; 4) effects of hormone therapy; and 5) efficacy of other therapies (eg, psychotherapy, exercise, and natural health products). Overall, evidence generally suggests that most midlife women who experience a major depressive episode during the perimenopause have experienced a prior episode of depression. Midlife depression presents with classic depressive symptoms commonly in combination with menopause symptoms (ie, vasomotor symptoms, sleep disturbance), and psychosocial challenges. Menopause symptoms complicate, co-occur, and overlap with the presentation of depression. Diagnosis involves identification of menopausal stage, assessment of co-occurring psychiatric and menopause symptoms, appreciation of the psychosocial factors common in midlife, differential diagnoses, and the use of validated screening instruments. Proven therapeutic options for depression (ie, antidepressants, psychotherapy) are the front-line treatments for perimenopausal depression. Although estrogen therapy is not approved to treat perimenopausal depression, there is evidence that it has antidepressant effects in perimenopausal women, particularly those with concomitant vasomotor symptoms. Data on estrogen plus progestin are sparse and inconclusive.

Effect of Flibanserin Treatment on Body Weight in Premenopausal and Postmenopausal Women with Hypoactive Sexual Desire Disorder: A Post Hoc Analysis.

BACKGROUND: Flibanserin, a 5-HT1A agonist and 5-HT2A antagonist, is indicated for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. This post hoc analysis evaluated the effect of flibanserin treatment on body weight in premenopausal and postmenopausal women with HSDD. MATERIALS AND METHODS: This analysis included three 24-week, double-blind, placebo-controlled studies of flibanserin 100 mg each bedtime (qhs) in premenopausal women, a similarly designed study in postmenopausal women, and a 52-week, open-label extension study in premenopausal women. RESULTS: In a pooled analysis of premenopausal women, mean baseline body mass index (BMI) was 27.0 kg/m2 in the flibanserin group (n = 1227) and 26.8 kg/m2 in the placebo group (n = 1238). Among patients who completed 24 weeks of treatment, least squares (LS) mean weight change was -1.4 kg in the flibanserin group (n = 1010) and -0.1 kg in the placebo group (n = 1066; p < 0.0001). Weight loss ≥5% from baseline was reported in 21.0% of patients who received flibanserin and 7.8% of patients who received placebo; weight loss ≥10% was reported in 3.8% and 2.0% of patients, respectively. In postmenopausal women, mean baseline BMI was 27.7 kg/m2 in the flibanserin group (n = 467) and 27.3 kg/m2 in the placebo group (n = 480). LS mean weight change at week 24 was -1.8 kg in the flibanserin group (n = 385) and -0.1 kg in the placebo group (n = 425; p < 0.0001), with weight loss ≥5% reported in 24.7% and 7.3% of patients, respectively, and weight loss ≥10% reported in 5.2% and 1.7%, respectively. In HSDD patients with >12 months (n = 880) and >18 months (n = 637) of exposure to flibanserin, mean weight change was -1.0 and -1.2 kg, respectively; 25.4% and 26.9% of patients, respectively, experienced weight loss ≥5% from baseline, and 7.8% and 8.4%, respectively, experienced weight loss ≥10%. CONCLUSIONS: Women treated with flibanserin for HSDD may experience weight loss.