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Depression, with or without concomitant anxiety, is one of the most burdensome medical conditions worldwide. Depression affects women more often than men and may cause significant impairment. Reproductive phase-related windows of vulnerability for depression (new or recurrent) have been recognized, including the menopause transition. Midlife depression is likely influenced by both menopause- and nonmenopause-related factors. Antidepressants and cognitive behavioral therapy remain first-line treatment options for moderate to severe major depressive disorder at any time, with proven efficacy and tolerability in midlife women. Transdermal estradiol can also be part of the treatment armamentarium, but its use as a prophylaxis against midlife depressive symptoms, although promising, warrants further investigation.

Background Patients who present to emergency departments after intentional self-harm are at an increased risk of dying by suicide. This applies particularly to men, who represent nearly two-thirds of those who die by suicide in Ontario. One way of potentially addressing this gap is to offer a course of blended problem-solving therapy, comprised of a brief course of evidence-based psychotherapy for individuals at risk for suicide, facilitated by the use of a patient-facing smartphone application and a clinician-facing “dashboard.” This approach has the potential to combine the benefits of face-to-face therapy and technology to create a novel intervention. Methods This is a cohort study nested within a larger pragmatic multicentre pre- and post-design cluster randomised trial. Suicidal ideation assessed by the Beck Scale for Suicide Ideation is the primary outcome variable. Secondary outcome measures include depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder 7-item scale), post-traumatic stress disorder (Primary Care PTSD Screen), health-related quality of life (EuroQol 5-dimension 5-level questionnaire), meaning in life (Experienced Meaning in Life Scale), perceived social supports (Multidimensional Scale of Perceived Social Support), alcohol use (Alcohol Use Disorders Identification Test), drug use (Drug Abuse Screening Test Short Form 10), problem-solving skills (Social Problem-Solving Inventory–Revised Short Form), and self-reported healthcare costs, as well as health service use measured using Ontario administrative health data. A process evaluation will also be conducted following study completion. Discussion The cohort study will test whether better adherence to the intervention results in better outcomes. The value of the cohort study design is that we can examine in more detail certain subgroups or other variables that are not available in the larger cluster randomised trial. This trial will aim to improve standards by informing best practice in management of men who self-harm and present to hospitals in Ontario. Trial registration ClinicalTrials.gov, NCT03473535. Registered on March 22, 2018.

Most ovulatory women experience premenstrual symptoms (premenstrual syndrome, molimina) which indicate impending menstruation and are of little clinical relevance because they do not affect quality of life. A few women, however, experience significant physical and/or psychological symptoms before menstruation that, if left untreated, would result in deterioration in functioning and relationships. The precise etiology remains elusive, although new theories are gaining support in pre-clinical and early clinical trials. Refined diagnostic criteria allow better discrimination of this condition from other psychiatric diagnoses and the selection of symptom appropriate therapies that afford relief for most women. Pharmacotherapies (particularly selective serotonin reuptake inhibitors and SNRIs) represent the first-line treatment for premenstrual dysphoric disorder and severe, mood-related premenstrual syndrome. Continuous combined oral contraceptives have limited evidence for usefulness in premenstrual dysphoric disorder, whereas medical ovarian suppression is often recommended for patients who fail to respond or cannot tolerate first-line treatments (e.g., selective serotonin reuptake inhibitors). The use of cognitive behavioural therapies is promising, but it remains limited by sparse data and restricted access to trained professionals. A proper diagnosis (particularly the distinction from other underlying psychiatric conditions) is crucial for the implementation of effective therapy and alleviation of this impairing condition.

Objective Provide strategies for improving the care of perimenopausal and postmenopausal women based on the most recent published evidence. Target Population Perimenopausal and postmenopausal women. Benefits, Harms, and Costs Target population will benefit from the most recent published scientific evidence provided via the information from their health care provider. No harms or costs are involved with this information since women will have the opportunity to choose among the different therapeutic options for the management of the symptoms and morbidities associated with menopause, including the option to choose no treatment. Evidence Databases consulted were PubMed, MEDLINE, and the Cochrane Library for the years 2002–2020, and MeSH search terms were specific for each topic developed through the 7 chapters. Validation Methods The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations of strong and weak recommendations). Intended Audience physicians, including gynaecologists, obstetricians, family physicians, internists, emergency medicine specialists; nurses, including registered nurses and nurse practitioners; pharmacists; medical trainees, including medical students, residents, fellows; and other providers of health care for the target population. SUMMARY STATEMENTS 1 The perimenopausal period is a window of vulnerability for the development of depressive symptoms and major depressive episodes, even in women with no history of depression (high). 2 Factors related and unrelated to menopause contribute to the occurrence and severity of mood symptoms in mid-life. Factors related to menopause are those that are context-related or timing-related, such as vasomotor symptoms, sleep disturbances, and health problems, whereas those unrelated to menopause represent a continuum of risk that precedes menopause, or longitudinal risk factors, such as unemployment, smoking, and lifetime history of anxiety (high). 3 Recent large-scale studies show an elevated risk of depression in women following hysterectomy, with or without oophorectomy. A history of primary ovarian insufficiency, which occurs in 1% of women, is also associated with an increased risk of depression (high). 4 Poor sleep quality, as measured both subjectively and objectively, is common among women in the perimenopausal and postmenopausal periods (high). 5 Cognitive symptoms, such as worsening memory and slower cognitive speed, are often reported among newly menopausal women, and these symptoms have been demonstrated in prospective, longitudinal studies (moderate). RECOMMENDATIONS 1 Proven therapeutic options for depression at any life stage (i.e., antidepressants, cognitive behavioural therapy, and other behaviour-based psychotherapies) should remain the first-line treatment options for depressive symptoms and episodes during the menopausal transition and postmenopausal years (strong, high). 2 For women experiencing recurrent episodes of depression during the perimenopausal period, selection of antidepressants should consider the patient's response to and toleration of previous trials of antidepressants (strong, moderate). 3 For women experiencing new-onset depression, both adverse effects (e.g., sexual dysfunction, weight changes) and drug–drug interactions (e.g., between specific selective serotonin reuptake inhibitors and tamoxifen) specific to this population should be considered (strong, moderate). 4 There is some evidence that hormone therapy has antidepressant effects similar in magnitude to those observed with classic antidepressant agents in perimenopausal women with depression, with or without concomitant vasomotor symptoms (strong, high). However, hormone therapy is ineffective in treating depressive disorders in postmenopausal women, suggesting a possible window of opportunity for the antidepressant benefits of hormone therapy in perimenopause (strong, moderate). 5 The approach to poor sleep during the menopausal transition should initially include education about sleep hygiene, and primary sleep disorders should be ruled out (strong, high). 6 Vasomotor symptoms are a significant contributor to sleep disruption and should be addressed; hormone therapy may improve sleep when vasomotor symptoms are present (strong, high). 7 Several other therapies for sleep have shown benefit, including cognitive behavioural therapy–insomnia (strong, high), aerobic exercise, eszopiclone, venlafaxine, black cohosh, and valerian root (strong, moderate). 8 For women with cognitive complaints, lifestyle modifications are recommended to decrease the risk of cognitive decline. These include increasing aerobic exercise and including vegetables in the diet more often, as well as limiting the potential influence of hypertension, diabetes, and atherosclerotic disease (strong, high). 9 Menopausal hormone therapy has not been shown to significantly improve measures of cognitive function over several years of use (strong, moderate).

Depression is a disabling condition, which often leads to significant personal, societal, and economic costs. Windows of vulnerability for depression in women likely are associated with an increased sensitivity experienced by some women to changes in the hormonal milieu that occur during the luteal phase of their cycles, during the postpartum period, and/or during the menopause transition. The controversy surrounding a menopause-related depression has been fueled by conflicting methodologies used to characterize reproductive staging or assess psychiatric conditions during midlife years.

As a recurrent, cyclical phenomenon, premenstrual syndrome (PMS) affects a significant proportion of women of the reproductive age, and leads to regular monthly days of functional impairment. Symptoms of PMS include somatic and psychological symptoms, such as headaches, sleep disturbances, social withdrawal and mood changes, during the late luteal phase of the menstrual cycle, which alleviate during the follicular phase. This study investigated neurocognitive functioning in women with moderate to severe PMS symptoms (n=13) compared to women with mild/no PMS (n=27) through administration of a battery of neuropsychological tests during the asymptomatic follicular phase of the menstrual cycle. Relative to women with mild/no PMS symptoms, women with moderate to severe PMS showed significantly poorer accuracy and more errors of omission on the N-0-back, as well as more errors of omission on the N-2-back task, indicating the presence of impairment in selective attention and working memory. This study provides evidence of persistent, subtle working memory and selective attention difficulties in those with moderate to severe PMS during the follicular phase of the menstrual cycle.

This prognostic study of patients with major depressive disorder estimates how accurately an outcome of escitalopram treatment can be predicted from electroencephalographic data., Key Points Question Is it possible to predict whether the condition of a patient with depression will improve after escitalopram treatment by analyzing their resting-state electroencephalographic signals? Findings In this prognostic study of data from 122 patients diagnosed with major depressive disorder, support vector machine classifiers demonstrated an accuracy of 82.4% for predicting escitalopram treatment outcome. Meaning When complemented by appropriate analysis methods, resting-state electroencephalographic recordings may be instrumental in improving treatment of patients with depression., Importance Social and economic costs of depression are exacerbated by prolonged periods spent identifying treatments that would be effective for a particular patient. Thus, a tool that reliably predicts an individual patient’s response to treatment could significantly reduce the burden of depression. Objective To estimate how accurately an outcome of escitalopram treatment can be predicted from electroencephalographic (EEG) data on patients with depression. Design, Setting, and Participants This prognostic study used a support vector machine classifier to predict treatment outcome using data from the first Canadian Biomarker Integration Network in Depression (CAN-BIND-1) study. The CAN-BIND-1 study comprised 180 patients (aged 18-60 years) diagnosed with major depressive disorder who had completed 8 weeks of treatment. Of this group, 122 patients had EEG data recorded before the treatment; 115 also had EEG data recorded after the first 2 weeks of treatment. Interventions All participants completed 8 weeks of open-label escitalopram (10-20 mg) treatment. Main Outcomes and Measures The ability of EEG data to predict treatment outcome, measured as accuracy, specificity, and sensitivity of the classifier at baseline and after the first 2 weeks of treatment. The treatment outcome was defined in terms of change in symptom severity, measured by the Montgomery-Åsberg Depression Rating Scale, before and after 8 weeks of treatment. A patient was designated as a responder if the Montgomery-Åsberg Depression Rating Scale score decreased by at least 50% during the 8 weeks and as a nonresponder if the score decrease was less than 50%. Results Of the 122 participants who completed a baseline EEG recording (mean [SD] age, 36.3 [12.7] years; 76 [62.3%] female), the classifier was able to identify responders with an estimated accuracy of 79.2% (sensitivity, 67.3%; specificity, 91.0%) when using only the baseline EEG data. For a subset of 115 participants who had additional EEG data recorded after the first 2 weeks of treatment, use of these data increased the accuracy to 82.4% (sensitivity, 79.2%; specificity, 85.5%). Conclusions and Relevance These findings demonstrate the potential utility of EEG as a treatment planning tool for escitalopram therapy. Further development of the classification tools presented in this study holds the promise of expediting the search for optimal treatment for each patient.

Introduction: Insomnia in Major Depressive Disorder (MDD) is highly prevalent and associated with increased suffering and functional impairment. Effective, evidence-based treatments for insomnia in MDD are an unmet need in clinical practice.Areas covered: Herein, the authors provide a review of the clinical correlates, putative neurobiological mechanisms and treatment options for the management of insomnia in individuals with MDD.Expert opinion: Sleep disturbances in MDD should be recognized as at least one of the following: (1) a domain of depressive psychopathology; (2) a consequence of rhythm disruptions; (3) a manifestation of comorbidities of sleep disturbances; (4) a manifestation of the influence of sex hormones in the brain in MDD; (5) a general medical comorbidity; and (6) a side effect of antidepressant medications. Assessment of insomnia in clinical practices is routinely performed with the use of non-structured interviews. Other methods such as standardized questionnaires and sleep diaries, along with complementary methods such as actigraphy and polysomnography are more scarcely applied. Smartphones and personal devices offer a promising strategy with the use of passive, long lasting, and ecologically valid assessments despite the lack of studies specifically targeting insomnia in individuals with MDD. New therapeutic approaches are essential, including novel targets such as orexins/hypocretins and the endocannabinoid system.

Depression affects one in every five adults in North America. Women are more affected than men, possibly because of genetics, coping strategies, and hormone variations. The concept of a menopause-associated depression, however, remains a complex and controversial topic. Although hormone therapy is not recommended as first-line therapy for depression in midlife women, estrogen-based hormone therapy may minimize the need for or enhance the response to antidepressant or behavior-based therapies in select perimenopausal women.

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.

e16062 Background: Testicular cancer survivors may experience long-term psychological distress related to their diagnosis and treatment. Measurement of mental health service use (MHS) is an objective way to quantify the incurred burden of psychological distress. Here we describe patterns of MHS use among survivors of testicular cancer in a single-payer health system. Methods: The Ontario Cancer Registry was linked to electronic treatment records to identify all incident cases of testicular cancer treated with orchiectomy in the Canadian province of Ontario during 2004-2010. Mental health clinical visits were identified from records of hospital admission, emergency room visits and out-patient physician billing records. Results: The study cohort included 1877 patients; mean age was 35 and 61% had pure seminoma. Two thirds of patients (66%, 1230/1877) were initially treated with active surveillance. In the 2-year period prior to orchiectomy, 24% (443/1877) of patients had MHS use. Post-orchiectomy, the prevalence of MHS use was 18% (331/1877), 23% (431/1877) and 30% (572/1877) at 6, 12 and 24 months, respectively. The use of MHS was greatest in the peri-diagnostic/surgical period. Rates of MHS visits, 3 months before, 0-3 months after, 4-6 months after and 2 years after orchiectomy were 11%, 14%, 10%, and 6%, respectively. Post-orchiectomy MHS use was greatest among those with baseline MHS use. The prevalence of MHS use for patients with and without baseline MHS use was 40% (175/443) vs 11% (156/1434, p < 0.001) at 6 months; 51% (225/443) vs 14% (206/1434, p < 0.001) at 12 months; and 61% (271/443) vs 21% (301/1434, p < 0.001) at 24 months post-orchiectomy. Post-orchiectomy MHS use did not vary by initial treatment strategy (active surveillance vs upfront treatment, p = 0.435). Older patients were more likely to have MHS visits at all time periods than younger patients; MHS rates at 6 months were 15% (93/631) vs 18% (112/625) vs 20% (126/621) for ages 16-29, 30-39, and 40+ years respectively (p = 0.035). Conclusions: MHS use among survivors of testicular cancer is common, particularly in the peri-diagnostic and surgical period. The rate of MHS use is highest among those patients with a history of prior MHS use. Clinicians should screen for the presence of psychological distress among survivors of testicular cancer.

Menopausal transition and early postmenopausal years have been described as a "window of vulnerability" for the development of depressive symptoms or depression (new or recurrent) in some women. This article aims to review contributing factors to the emergence of menopause-related depression, some of the key challenges to its proper identification and management, and evidence on effective treatment strategies.A body of evidence (animal data, epidemiologic studies, and clinical studies) was reviewed to disentangle some of the complex interactions between changes in sex hormones and reproductive function, physical health, and mood in midlife women. Special focus was given to the window of vulnerability framework.Despite evidence of a critical window for new onset of depression, a prior depressive episode (particularly if related to reproductive events) remains the strongest predictor of mood symptoms or depression during midlife years. Vasomotor symptoms, anxiety, and other health-related issues also modulate the risk for depression. Mechanistically, estrogen plays an important role in mood and cognitive regulation. Transdermal estradiol, as well as serotonergic and noradrenergic antidepressants, have shown efficacy in the management of depression in this population. Other evidence-based treatment options (hormonal, pharmacologic, and behavioral) are available to clinicians and health professionals.A more comprehensive diagnostic approach should be used in symptomatic midlife women. Ultimately, researchers hope to develop preventive strategies and treatments that could be tailored to multiple symptom domains and improve overall functioning.

Epidemiologic and clinic data have unequivocally supported the notion that women experience more psychiatric problems at some point in their lives compared with men, particularly mood and anxiety symptoms and sleep problems. It is also known that, for some women, such increased risk might be associated with reproductive cycle events such as the postpartum period or the menopausal transition. These periods are not only marked by substantial hormone variations but also quite often accompanied by stressful events and changes in personal, family and professional responsibilities. The complexity of these reproductive-related 'windows of vulnerability' poses a challenge to physicians and other professionals dedicated to women's health across the lifespan. The menopausal transition and early postmenopausal years constitute a characteristic example; during this period in life, dynamic changes in sex hormones and reproductive function co-occur with modifications in metabolism, sexuality, lifestyle behaviours and overall health, sometimes affecting a woman's quality of life and overall functioning. For most women, however, this transition has little or no significant impact on their mental wellness. A prior depressive episode--particularly if related to reproductive events--is the strongest predictor of mood symptoms or depression during menopausal years. Also, the presence and severity of vasomotor symptoms and other health-related issues appear to modulate the risk for depression in midlife women. Mechanistically, estrogen plays an important modulatory role in mood and cognitive regulation, hence the effects noted when midlife women are exposed to significant estrogen fluctuations or to estrogen-based therapies (use or withdrawal). Transdermal estradiol, as well as serotonergic and noradrenergic antidepressants, have shown efficacy in the management of depression in this population. Other evidence-based treatment options (hormonal, pharmacological, behavioural) are available to clinicians and health professionals who care for this population.

Background This study aims to compare the effectiveness of EEG frequency band activity including interhemispheric asymmetry and prefrontal theta cordance in predicting response to escitalopram therapy at 8-weeks post-treatment, in a multi-site initiative. Methods Resting state 64-channel EEG data were recorded from 44 patients with a diagnosis of major depressive disorder (MDD) as part of a larger, multisite discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). Clinical response was measured at 8-weeks post-treatment as change from baseline Montgomery-Asberg Depression Rating Scale (MADRS) score of 50% or more. EEG measures were analyzed at (1) pre-treatment baseline (2) 2 weeks post-treatment and (3) as an ‘‘early change” variable defined as change in EEG from baseline to 2 weeks post-treatment. Results At baseline, treatment responders showed elevated absolute alpha power in the left hemisphere while non-responders showed the opposite. Responders further exhibited a cortical asymmetry in the parietal region. Groups also differed in pre-treatment relative delta power with responders showing greater power in the right hemisphere over the left while non-responders showed the opposite. At 2 weeks post-treatment, responders exhibited greater absolute beta power in the left hemisphere relative to the right and the opposite was noted for non-responders. A reverse pattern was noted for absolute and relative delta power at 2 weeks post-treatment. Responders exhibited early reductions in relative alpha power and early increments in relative theta power. Non-responders showed a significant early increase in prefrontal theta cordance. Conclusions Hemispheric asymmetries in the alpha and delta bands at baseline and at 2 weeks post-treatment have moderately strong predictive utility in predicting response to antidepressant treatment.

Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers (“biomarkers”) of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication. The primary objective of this initial study (known as CAN-BIND-1) is to identify individual and integrated neuroimaging, electrophysiological, molecular, and clinical predictors of response to sequential antidepressant monotherapy and adjunctive therapy in MDD. CAN-BIND-1 is a multisite initiative involving 6 academic health centres working collaboratively with other universities and research centres. In the 16-week protocol, patients with MDD are treated with a first-line antidepressant (escitalopram 10–20 mg/d) that, if clinically warranted after eight weeks, is augmented with an evidence-based, add-on medication (aripiprazole 2–10 mg/d). Comprehensive datasets are obtained using clinical rating scales; behavioural, dimensional, and functioning/quality of life measures; neurocognitive testing; genomic, genetic, and proteomic profiling from blood samples; combined structural and functional magnetic resonance imaging; and electroencephalography. De-identified data from all sites are aggregated within a secure neuroinformatics platform for data integration, management, storage, and analyses. Statistical analyses will include multivariate and machine-learning techniques to identify predictors, moderators, and mediators of treatment response. From June 2013 to February 2015, a cohort of 134 participants (85 outpatients with MDD and 49 healthy participants) has been evaluated at baseline. The clinical characteristics of this cohort are similar to other studies of MDD. Recruitment at all sites is ongoing to a target sample of 290 participants. CAN-BIND will identify biomarkers of treatment response in MDD through extensive clinical, molecular, and imaging assessments, in order to improve treatment practice and clinical outcomes. It will also create an innovative, robust platform and database for future research. ClinicalTrials.gov identifier NCT01655706 . Registered July 27, 2012.

During the postpartum period, some women might be under a considerable amount of stress and at increased risk for on-set or exacerbation of obsessive-compulsive disorder (OCD). Little is known about the stress response correlates during the postpartum period and in patients with OCD. This study aimed to examine the cerebral, psychologic and endocrine correlates of the stress response in patients with OCD and during the postpartum period.Women with postpartum OCD, healthy postpartum women and healthy mothers past the postpartum period underwent functional magnetic resonance imaging while facing a reliable psychosocial stressor (the Montreal Imaging Stress Task). Stress-related psychologic and endocrine responses (i.e., cortisol) were obtained.We enrolled 12 women with postpartum OCD, 16 healthy postpartum women and 11 healthy mothers past the postpartum period in our study. Compared with healthy postpartum counterparts, postpartum women with OCD had a heightened self-reported and endocrine stress response associated with a distinct brain activation pattern in response to psychosocial stress involving the orbitofrontal and temporal cortices. Moreover, compared with mothers assessed in a period of time beyond the postpartum period, healthy postpartum women did not differ in psychologic and cortisol response to stress, but recruited different brain regions, such as the dorsolateral prefrontal cortex and the anterior cingulate cortex, during exposure to stress.Potential confounding factors, such as medication use, breastfeeding, parity and personality factors, may have modulated the stress-related endocrine response and could not be assessed in this study.Obsessive-compulsive disorder and the postpartum period differentially influence the brain circuitry underlying psychosocial stress as well as the psychologic and endocrine responses.

This NIA-sponsored workshop was aimed at understanding the impact of the menopausal transition on mood symptoms and cognitive disorders during the menopausal transition and identifying research priorities for further investigation. Longitudinal studies provide insights into the frequency of these problems in representative samples of midlife women. The majority of women do not experience serious depressive symptoms during the transition, but a subgroup of women is at increased risk. Slight changes in memory function and processing speed are evident during the transition, and physiological factors associated with hot flashes may contribute to memory problems. Clinical trial evidence indicates that estradiol therapy can be effective in treating perimenopausal depression. There is some limited evidence of a cognitive benefit with estrogen alone therapy in younger postmenopausal women, and stronger evidence that certain forms of combination hormone therapy produce modest deficits in verbal memory in younger and older women. Identifying a cognitively neutral or beneficial combination therapy for the treatment of menopausal symptoms in naturally menopausal women is an important goal for future research. Pharmacological challenge studies bridge the basic science and clinical literatures to provide insights into the extent to which changes in endogenous and exogenous hormones and other neurotransmitter systems contribute to cognitive and mood problems. Routine evaluation of depressive symptoms in perimenopausal women is warranted by the literature. Quick and valid screening tools for assessing depression in the clinic are available on-line and free of charge.

The menopausal transition is often marked by physical symptoms (e.g., vasomotor and sexual) and is sometimes accompanied by emotional changes that follow the decline in ovarian functioning. Although the absolute majority of women experience a smooth transition into postmenopausal years, this period in a woman's life has been associated, in some cases, with higher risk to develop depressive symptoms.

Onset/worsening of obsessive-compulsive disorder (OCD) during the perinatal period are frequently seen clinically. No specific tool assessing the unique content, context, severity, and onset of perinatal OCD exists. A self-report scale of perinatal obsessions and compulsions, the Perinatal Obsessive-Compulsive Scale (POCS), was developed and validated. A total of 162 women (67 pregnant, 95 postpartum) participated in this pilot study. They completed the POCS as well as the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). The POCS has good construct validity, reflected by representative items, high internal consistency, good concurrent validity and discriminative capacity. The most common obsessions were fear of having an unhealthy baby at birth, contamination, the baby being taken away, and infant death. Behavioral compulsions such as repeating rituals, asking for reassurance, checking, and cleaning mirrored these obsessions. The POCS helps clinicians detect perinatal OCD while giving perinatal women an opportunity to openly discuss socially sensitive issues.

The Premenstrual Symptoms Screening Tool was modified for use in adolescents and piloted in 578 girls at three international sites. Nearly one third (29.6%) reported experiencing severe PMS or PMDD, with irritability being the most commonly reported symptom. Rates of menstrual-related pain were high, particularly in those with severe PMS or PMDD. Severe PMS and PMDD present with similar rates and symptoms in adolescents as in adults, and the Premenstrual Symptoms Screening Tool modified for adolescents is a fast, reliable tool to screen for these syndromes in adolescents.

Postpartum onset and/or worsening of anxiety disorders, particularly of obsessive-compulsive disorder (OCD) are scarcely reported in the literature although frequently observed in the clinical setting. These obsessions and compulsions focus primarily on the newborn and create immense distress in the mother. Research on the stress response in postpartum mothers is limited and the neuroendocrine correlates of OCD in particular are unclear. The aim of this pilot study was to compare the physiological and subjective responses to a physical stressor, the Cold Pressor Test (CPT), in postpartum women with OCD in comparison to healthy controls. Saliva samples were collected during the CPT and analyzed for cortisol and alpha-amylase (AA). Statistical analyses demonstrated a significant main effect of time with the CPT eliciting an increase in cortisol (p=0.002) and alpha-amylase (p=0.02) with a lot of variance in cortisol and AA stress responses in women suffering from OCD; in addition, postpartum women with OCD had higher cortisol levels compared to controls (main effect of group t: p=0.001). Overall, women with OCD reported experiencing more subjective stress and anxiety (p=0.006 and p=0.002, respectively) and found the CPT more stressful than healthy postpartum women (p=0.05). This is the first study investigating the subjective and endocrine stress responses in postpartum women suffering from OCD. Our findings demonstrate cortisol hyperactivity and higher CPT-related subjective stress ratings in postpartum OCD women but no group difference in adrenergic activity and in the magnitude of the stress-related endocrine increases following a physical stressor.

SUMMARY Premenstrual mood symptoms are common and a small but significant proportion ofwomenexperiencerecurrentpremenstrualmoodsymptomsthataresevereenoughtocause substantial social and occupational dysfunction. There is convincing evidencefor important roles for biological and sociocultural variables in the development ofpremenstrual mood symptoms. There are several effective treatments, used aloneor in combination, that have been found to ameliorate psychological symptoms asso-ciated with the menstrual cycle. Further interdisciplinary research into risk factors forPMDD, and the interaction between them, will provide a more complete under-standing of the cause of this disorder, and ultimately guide future developments intreatment. REFERENCES 1. Delaney J, Lupton MJ, Toth E. The curse: a cultural history of menstruation. NewYork: E.P. Dutton; 1976.2. Chrisler JC, Johnston-Robledo I. Raging hormones? Feminist perspectives onpremenstrual syndrome and postpartum depression. In: Ballou M, Brown LS,editors. Rethinking mental health and disorder: feminist perspectives. NewYork: Guilford Press; 2002. p. 174–97.3. American Psychiatric Association. Diagnostic and statistical manual of mentaldisorders. Text revision (DSM-IV-TR). Fourth edition. Washington, DC: AmericanPsychiatric Association; 2000. p. 771–4.4. American College of Obstetricians and Gynecologists. Premenstrual syndrome.Patient Education Pamphlet, by the American College of Obstetriciansand Gynecologists; 2003. Available at: www.acog.org/publications/patient_education/bp057.cfm. Accessed February 16, 2010.5. Wittchen HU, Becker E, Lieb R, et al. Prevalence, incidence and stability ofpremenstrual dysphoric disorder in the community. Psychol Med 2002;32:119–32.6. Steiner M, Macdougall M, Brown E. The premenstrual symptoms screening tool(PSST) for clinicians. Arch Womens Ment Health 2003;6(3):203–9.7. Takeda T, Tasaka K, Sakata M, et al. Prevalence of premenstrual syndrome andpremenstrual dysphoric disorder in Japanese women. Arch Womens MentHealth 2006;9(4):209–12.8. Cohen LS, Soares CN, Otto MW, et al. Prevalence and predictors of premen-strual dysphoric disorder (PMDD) in older premenopausal women. The HarvardStudy of Moods and Cycles. J Affect Disord 2002;70:125–32.9. Rivera-Tovar AD, Frank E. Late luteal phase dysphoric disorder in youngwomen. Am J Psychiatry 1990;147:1634–6.10. Banerjee N, Roy KK, Takkar D. Premenstrual dysphoric disorder—a study fromIndia. Int J Fertil Womens Med 2000;45:342–4.

This pooled analysis evaluated the efficacy of desvenlafaxine (administered as desvenlafaxine succinate) for the treatment of major depressive disorder (MDD) in patients grouped by age and sex. Nine clinical trials were pooled. Outpatients 18 years or older with MDD received desvenlafaxine 50, 100, 200, or 400 mg/d (men = 709; women = 1096) or placebo (men = 399; women = 709) for 8 weeks. Data were analyzed by sex and by age groups of 40 years and younger, 41 to 54 years, 55 to 64 years, and 65 years and older. The primary outcome was change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D17) total score at the final evaluation. Secondary measures included response (> or =50% reduction in HAM-D17) and remission (HAM-D17 < or =7). No significant sex-treatment, age-treatment, or sex-age-treatment interactions were observed. Differences in the HAM-D17 change from baseline for desvenlafaxine versus placebo were -1.72 for women (P < 0.001) and -2.11 for men (P < 0.001); these changes were significant among women of the 18-to-40 (P = 0.01), 41-to-54 (P = 0.002), and 65-years-and-older subgroups (P = 0.02), and significant among men for the 18-to-40 (P = 0.03) and 41-to-54 subgroups (P = 0.002). The response rates for desvenlafaxine and placebo were 53% and 42% (P < 0.001), respectively, among women, and 53% and 41% (P < 0.001), respectively, among men; the remission rates were 31% and 21% (P < 0.001) and 34% and 26% (P = 0.007), respectively. The response rates were similar across age subgroups, with significant differences from placebo observed in the 18-to-40 (P < or = 0.05), 41-to-54 (P < or = 0.005), and 65-and-older subgroups (P = 0.02). The remission rates were significant versus placebo in the 41-to-54 (P = 0.006), 55-to-64 (P = 0.01), and 65-and-older (P = 0.02) subgroups among women but not in any age subgroup among men. Desvenlafaxine generally improved depressive symptoms across age and sex subgroups.

It has long been recognized that women are at a higher risk than men to develop depression and that such risk is particularly associated with reproductive cycle events. Recent long-term, prospective studies have demonstrated that the transition to menopause is associated with higher risk for new onset and recurrent depression. A number of biological and environmental factors are independent predictors for depression in this population, including the presence of hot flushes, sleep disturbance, history of severe premenstrual syndrome or postpartum blues, ethnicity, history of stressful life events, past history of depression, body mass index, socioeconomic status and the use of hormones and antidepressants. Accumulated evidence suggests that ovarian hormones modulate serotonin and noradrenaline neurotransmission, a process that may be associated with underlying pathophysiological processes involved in the emergence of depressive symptoms during periods of hormonal fluctuation in biologically predisposed subpopulations. Transdermal estradiol and serotonergic and noradrenergic antidepressants are efficacious in the treatment of depression and vasomotor symptoms in symptomatic, midlife women. The identification of individuals whom might be at a higher risk for depression during menopausal transition could guide preventive strategies for this population.

Women seem to have a heightened risk for developing sleep disorders compared with men; women also show a greater risk for developing some psychiatric problems including mood and anxiety disorders. The modulatory effects of sex hormones on sleep-wake behaviors and mood may contribute to this compounded risk and to the emergence of symptoms throughout the female reproductive life cycle. This article focuses on the clinical evidence for sleep disorders in women. Particular attention is paid to the hormonal and mood interactions with sleep disorders (sleep initiation and sleep maintenance) in the context of menstrual cycle changes, pregnancy, and in the menopausal years. Lastly, management strategies for sleep disorders in women are critically discussed.

Objective: Despite the efficacy of antidepressants, depression can break through premenstrually. Oral contraceptive pills (OCPs) stabilize reproductive hormones and treat premenstrual dysphoric disorder. Management of depression that breaks through premenstrually has not been studied. Method: Women taking antidepressants with successfully treated depression, except during the late luteal phase (Montgomery-Asberg Depression Rating Scale [MADRS] score ≥ 15) and high late-luteal phase (Daily Rating of Severity of Problems scores) were randomly assigned to open-label ethinyl estradiol (EE) 30 tig/day plus drospirenone 3 mg/day (EE/DRSP) for 21 days and double-blinded treatment with EE 30 μg/day or placebo for days 22 through 28 of 2 cycles. Participants were recruited from community and psychiatry outpatient clinics and enrolled into this study in 2004-2005. Results: Of 25 subjects who received EE/DRSP (N = 12 with EE and N = 13 with placebo), 21 completed treatment. For study completers, premenstrual MADRS (p =.0019) and Daily Rating of Severity of Problems scores (p =.0001) improved significantly in both groups. Outcome did not differ between groups. Conclusion: This study provides preliminary evidence that addition of EE/DRSP (± EE) to antidepressants may treat premenstrual breakthrough of depression. Stabilizing hormone levels with EE/DRSP may provide an important therapeutic option for women taking antidepressants whose symptoms break through premenstrually.

The menopausal transition may impose a challenge to clinicians and health professionals who are invested in improving women's quality of life; after all, this period in life is commonly marked by significant hormone fluctuations accompanied by bothersome vasomotor symptoms (e.g., hot flushes and night sweats) and other somatic complaints. In addition, more recent epidemiologic data demonstrate that some women transitioning to menopause may be at higher risk for developing depression when compared with their risk during premenopausal years; this increased risk appears to be true even among those who had never experienced depression before. In this article, putative contributing factors for this window of vulnerability for depression during the menopausal transition are critically reviewed. Hormonal and nonhormonal factors that may contribute to the occurrence of physical and/or psychiatric complaints during the menopausal transition are discussed. Lastly, existing evidence-based treatment strategies are summarized.

BACKGROUND: Postmenopausal women with depression frequently have co-occurring symptoms of hot flashes (vasomotor symptoms), sleep disturbance, anxiety, and pain. Treatment strategies that target all of these symptoms together have not been investigated to date. METHOD: Study participants were postmenopausal women, 40 to 60 years old, with major depressive disorder (DSM-IV criteria) and vasomotor symptoms. The study design included a 2-week, single-blind placebo run-in phase followed by an 8-week open-label flexible-dosing (60-120 mg per day) study of duloxetine for women who did not respond to placebo. The primary outcome measure was change in Montgomery-Asberg Depression Rating Scale (MADRS) score during 8 weeks of duloxetine therapy. Secondary outcome measures included changes in vasomotor symptoms, sleep quality, anxiety, and pain. Analyses were conducted using non-parametric methods. Patients were enrolled in the study from May 31, 2005, through May 22, 2006. RESULTS: Of 30 women eligible to participate in this study, 20 initiated treatment with open-label duloxetine. Fourteen (70.0%) of these women completed the study. There was a statistically significant decrease in MADRS scores after 8 weeks of treatment (p < .001), with scores declining from 19.0 (interquartile range [IQR] = 15.0-21.0) to 5.5 (IQR = 3.0-9.0). There was also a statistically significant improvement in vasomotor symptoms (p = .003), anxiety (p = .002), sleep quality (p < .001), and pain (p < .05). CONCLUSIONS: Postmenopausal women with depression and vasomotor symptoms had significant improvement in depression, vasomotor symptoms, sleep, anxiety, and pain after 8 weeks of open-label duloxetine therapy. Given the common co-occurrence of these symptoms in postmenopausal women, duloxetine may offer important therapeutic benefits for postmenopausal women who have depression and menopause-related symptoms.

This article is part of a Special Issue "Estradiol and cognition". Subjective changes in concentration and memory are commonly reported by women during the second or third trimesters of pregnancy, but the nature of the problem is poorly understood. We hypothesized that these self-reports might reflect difficulties in working memory (WM). It was further hypothesized that antepartum depression (depression arising during pregnancy) may play an etiological role, either on its own or due to secondary changes in endocrine function or sleep. Using WM tasks that emphasized executive control processes mediated by the prefrontal cortex (PFC) we compared pregnant women tested at 34-36 weeks of gestation (n = 28) with age- and education-matched non-pregnant controls (n = 26). All pregnant women were screened for depression. Evidence of a WM disturbance was found, and was evident only among pregnant women showing depressive symptoms. In contrast, pregnant women who were not depressed showed WM performance that equalled, or even significantly exceeded, non-pregnant controls. No significant differences were observed on control tests of other cognitive functions. Multiple regression revealed that serum estradiol concentrations, along with severity of depressive affect but not sleep disruption, significantly predicted variation in the WM scores. In agreement with studies of estradiol and WM in other contexts, higher estradiol was associated with better WM, while higher levels of depressive symptoms predicted poorer WM. We conclude that memory disturbance during gestation might not be as widespread as commonly believed, but can be seen among women experiencing antepartum depression. The high level of WM performance found in healthy, non-depressed, pregnant women is discussed from an adaptationist perspective.

Several epidemiologic surveys suggest that insomnia occurs more frequently in women than men [1–3]. Overall, women have a 1.3- to 1.8-fold greater risk for developing insomnia [4]. Insomnia and other sleep disturbances are reported during specific situations associated with the female reproductive cycle, such as symptomatic premenstrual periods [5], pregnancy [6,7], and menopause [8]. Sleep patterns may change in older women, and sleep disorders become more frequent. These changes possibly are influenced by the emergence of coexisting medical conditions and the presence of other hormonal, physiologic, and even psychosocial factors [9–11]. Some reports suggest that women are more likely to experience insomnia during peri- and early postmenopausal years [12]. Insomnia is a common complaint during the menopausal transition, affecting up to 60% of women [13–15]. Putative causes of insomnia associated with the menopausal transition and postmenopausal years include the occurrence or severity of nocturnal hot flashes, mood disorders, and sleepdisordered breathing [8,16–18]. This article reviews what currently is known about sleep problems in women, with emphasis on common sleep disorders of particular relevance to various lifespan stages throughout the female reproductive lifecycle. Existing evidence on the clinical characteristics, risk factors, and treatment options for insomnia and sleep-disordered breathing in women and the potential implications of hormonal changes for their clinical management are discussed. This review focuses primarily on disorders of initiation and maintenance of sleep, which are some of the most common presenting complaints to physician practices.

More than 1.7 million American women are expected to reach menopause each year. Recent Canadian statistics show that a 50-year-old woman can now expect to live until her mid-80s, which implies living at least one-third of her life after menopause. The menopausal transition is typically marked by intense hormonal fluctuations, accompanied by vasomotor symptoms (eg, hot flashes, night sweats), sleeps disturbance, and changes in sexual function, as well as increased risk for osteoporosis, cardiovascular disease, and cognitive decline. More importantly, recent studies have demonstrated a significant association between menopausal transition and a higher risk for developing depression. In the post-Women's Health Initiative Study era, physicians and patients are questioning the safety and efficacy of long-term hormone therapy use. This article reviews the current literature on the benefits and risks of using hormone therapy for the treatment of menopause-related mood disturbances and alternate strategies currently available for the management of menopause-related problems, including antidepressants, complementary and alternative medicine, and selective estrogen receptor modulators.

Background: We assessed the impact of menopausal status on treatment response and well-being in a cohort of outpatient women with major depressive disorder (DSM-III-R criteria), who received treatment with fluoxetine (20 mg/day for 8 weeks). Methods: Menopausal status was defined based on age, presence of menstrual irregularity or amenorrhea and vasomotor symptoms. Remission and response of depression were defined as a 17-item Hamilton Depression Rating Scale (HAM-D-17) score ≤7 and a HAM-D-17 decrease ≧50%, respectively. Well-being was assessed by self-rating with the Symptom Questionnaire. Remitters were followed up for 28 additional weeks. Results: No differences in rates of response and remission as well as in levels of well-being were observed among pre- (n = 121), peri- (n = 28) and postmenopausal (n = 35) women at the endpoint of the acute phase, even after adjustment for baseline depression severity. Residual symptoms, however, were significantly more common in postmenopausal women, except for the continuation phase endpoint. Differences in residual symptoms during the acute phase subsided after adjustment for baseline depression severity. Conclusions: Overall, menopausal status did not significantly affect the response to fluoxetine treatment and the degree of posttreatment well-being among major depressive disorder patients.

Background: Consistent data on the prevalence and predictors of premenstrual dysphoric disorder (PMDD) in the general population are lacking. Methods: Premenstrual symptoms of 4164 women (aged 36-44 years) were retrospectively assessed by the Moos Premenstrual Inventory. From this original sample, 976 subjects were further interviewed at which time demographic and lifestyle characteristics, gynecologic history, and medical conditions were examined. The Structured Clinical Interview for DSM-IV Axis I disorders (SCID) was used to assess past and current psychiatric morbidity. Additionally, 513 of these women completed a prospective evaluation of premenstrual symptoms by using the Daily Rating of Severity of Problems Form (DRSP). Results: The diagnosis of PMDD was confirmed in 33 of 513 women (6.4%) who completed the prospective evaluation with daily records. Fourteen subjects (2.7%) met criteria for PMDD without a previous history of depression. PMDD was associated with lower education (odds ratio (OR) 5 2.3, confidence interval (CI) 5 1.1- 4.9), a history of major depression (OR 5 3.6, CI 5 1.7-7.4), and current cigarette smoking (OR 5 4.1, CI 5 1.5-11.1). In addition, women not working outside the home were significantly less likely to meet criteria for PMDD (OR 5 0.2, CI 5 0.1-0.9). Limitations: Only 513 of 976 women agreed to have their symptoms documented prospectively. Symptoms were assessed over the course of one menstrual cycle. Conclusions: This study indicates a significant prevalence of PMDD in a large community-based sample. Given the associated impairment in social and occupational functioning seen in PMDD, these prevalence data provide a strong rationale for enhanced recognition and treatment of the disorder.  2002 Elsevier Science B.V. All rights reserved.

O processo de envelhecimento promove alterações significativas na produção e no equilíbrio dos níveis circulantes de diversos hormônios sexuais em homens e mulheres. Acredita-se que esses hormônios (estrógenos, progestógenos, testosterona, dehidroepiandrosterona [DHEA]) exercem papel modulador sobre diversas funções psíquicas, particularmente sobre o humor e a cognição. Alterações nesse papel modulador causadas por variações abruptas dos hormônios sexuais circulantes -- como as que ocorrem, por exemplo, durante a transição menopausal -- favorecem o surgimento de queixas depressivas. No entanto, a utilização terapêutica de hormônios sexuais pode promover alívio ou mesmo remissão de sintomas depressivos, como já foi caracterizado com o uso de estradiol em mulheres em perimenopausa e com a administração de testosterona após a menopausa. Este artigo aborda, por revisão da literatura, os diversos papéis atribuídos aos hormônios sexuais no desenvolvimento e tratamento das queixas depressivas. Estudos sobre a eficácia terapêutica de estrógenos, testosterona e DHEA nos quadros depressivos são discutidos de forma crítica. Em essência, existem resultados preliminares bastante promissores, particularmente quanto ao uso de estradiol e testosterona em subpopulações específicas para alívio de sintomas depressivos. Futuras investigações devem melhor definir a utilização de hormônios como agente depressivo monoterápico ou adjuntivo, bem como delinear os riscos e as contra-indicações associados a seu uso. It has been demonstrated that aging has a significant impact on sex hormones production. It is now accepted that these hormones (including estrogens, progestogens, testosterone, and dehydroepiandrosterone [DHEA]) may play a pivotal role in the modulation of brain functioning, especially on mood and cognition. Changes in these modulatory effects due to abrupt sex hormonal fluctuations-as seen in the menopausal transition-contribute to the occurrence of mood disturbances. Hormonal interventions seem to improve depressive symptoms, as already demonstrated in studies of perimenopausal women treated with estradiol, and postmenopausal women treated with testosterone. This article reviews the potential role of sex hormones in the occurrence and treatment of depressive symptoms. Clinical studies on the antidepressant benefit of estrogens, testosterone, and DHEA are critically discussed. In essence, there are preliminary but promising data on the use of estradiol and testosterone for the treatment of depression in some specific sub-populations. Further studies would help to better delineate their therapeutic use (as monotherapy or adjunctive treatment), and to identify their limitations due to clinical contra-indications or risk of serious adverse events.

We examined the characteristics of 33 women with a diagnosis of premenstrual dysphoric disorder (PMDD) who did (n = 19) or did not (n = 14) report a history of major depression. Five hundred thirteen older premenopausal women (ages 36-44) from a community-based sample completed a prospective evaluation of PMDD with daily records. The diagnosis of PMDD was confirmed in 33 women (6.3%), and 14 subjects met criteria for PMDD with no history of depression. Demographic characteristics, cigarette smoking, and menstrual and reproductive history of subjects with PMDD who did or did not report a history of depression were compared. Women with PMDD and no history of depression were more educated and more frequently had a marital disruption (p0.05). No significant differences were observed with respect to reproduction-related characteristics or past cigarette smoking. These preliminary data suggest the existence of characteristics particularly related to women who meet criteria for PMDD and have no history of depression. Given the significant psychosocial impairment commonly associated with PMDD symptoms and the existing data that support its classification and adequate treatment as a distinct clinical entity, further studies are needed to better identify predictors of this syndrome unrelated to a lifetime history of depression.

The management of psychiatric disturbances during pregnancy, particularly depression and bipolar disorders, is complex. This article reviews the existing data regarding the impact of an untreated psychiatric illness on the infant's development. In addition, the potential risks to the fetus due to prenatal exposure to different psychotropic agents, including antidepressants, mood stabilizers, antipsychotics, and benzodiazepines, are summarized. Moreover, this article emphasizes that no decision is risk-free, and the ultimate goal is to reduce the exposure to both the illness and the potential teratogenic effects of the treatment. Therefore, clinicians should seek a treatment strategy, which poses the least risk for both mother and infant.

OBJETIVOS: A perimenopausa é freqüentemente associada ao surgimento de alterações físicas e emocionais. Estudos prévios indicam uma associação entre variações dos hormônios folículo-estimulante (FSH), luteinizante (LH) bem como de estrógenos e o surgimento de transtornos do humor, particularmente depressão. Este estudo investigou a correlação entre mudanças nos níveis de estradiol (E2) e FSH e a sintomatologia depressiva em mulheres na perimenopausa. MÉTODOS: Cinqüenta mulheres foram recrutadas nos atendimentos de uma clínica de menopausa e de um serviço psiquiátrico para realização de ensaio clínico com uso de 17 b-estradiol ou placebo. Selecionaram-se mulheres em perimenopausa (idade entre 40 e 55 anos, presença de alterações vasomotoras, irregularidade menstrual nos últimos 6 meses e/ou amenorréia há no máximo 12 meses, níveis de FSH>20 UI/L) e com diagnóstico de transtorno depressivo pelo DSM-IV (transtorno depressivo maior, transtorno distímico ou transtorno depressivo sem outra especificação). Dosagens séricas iniciais e finais (semana 12) de FSH e E2, bem como avaliações da sintomatologia depressiva (escores da MADRS) foram analisadas e suas correlações investigadas. RESULTADOS: As pacientes apresentaram mudanças (p 20 IU/L) were selected from a larger sample of patients attending specialized gynecologic (n=101) and psychiatric (n=75) outpatient services. They were randomized to receive treatment with patches of placebo or 17 b-estradiol for 12 weeks. Serum levels of estradiol and FSH, and scores on the Montgomery-Åsberg Depression Scale (MADRS) were used as outcome measures. RESULTS: There was a significant correlation between changes in MADRS scores and changes in FSH (r de Pearson=0.554, p

BackgroundThe predictive value of early functional improvement for treatment success at week 8 was assessed in a pooled analysis in patients with major depressive disorder (MDD).MethodsData were pooled from 7 double-blind studies in adult patients with MDD randomly assigned to desvenlafaxine 50 mg/d or placebo. Four levels of treatment success were determined at week 8 for patients with baseline Sheehan Disability Scale (SDS) score > 12 (N = 2156): functional response (SDS ≤12 and ≥50% improvement in SDS), functional/depression response (SDS ≤12 and ≥50% improvement in both SDS and 17-item Hamilton Rating Scale for Depression [HAM-D17] score), functional remission (SDS < 7), and functional/depression remission (SDS < 7 and HAM-D17 ≤7). Week 2 improvement in SDS was evaluated as a predictor of later functional response/remission using receiver operating characteristic analysis. Odds ratios (ORs) of the predictability of improvement thresholds were computed from a logistic regression model.ResultsThe proportion of patients achieving each level of treatment success was significantly greater for patients treated with desvenlafaxine (40%, 32%, 23%, 15%, respectively) vs placebo (31%, 22%, 17%, 10%; all P ≤ 0.002). Early change in SDS was a highly significant predictor of functional response/remission (ORs, 0.958–0.970; all P < 0.0001).DiscussionPatients’ early functional response to desvenlafaxine 50 mg/d is predictive of treatment success.

OBJECTIVE This post hoc analysis assessed the predictive value of improvement in depressive scores at early time points for treatment outcomes at week 8 in patients with major depressive disorder treated with desvenlafaxine 50 mg/d or placebo. METHODS Pooled data from 6 double-blind, fixed-dose studies in adult patients with major depressive disorder. Patients were randomly assigned to desvenlafaxine or placebo. Primary end point was change in 17-item Hamilton Rating Scale for Depression (HAM-D17) scores from baseline to week 8 (or last observation carried forward). Optimal thresholds of improvement (percent change from baseline HAM-D17) at weeks 2 and 3 for predicting 4 levels of treatment success (≥ 45%, ≥ 50%, and ≥ 65% decrease from baseline HAM-D17, HAM-D17 ≤ 7) at week 8 (last observation carried forward) were determined using receiver operating characteristic analysis. Odds ratios of the predictability of improvement thresholds were computed from a logistic regression model adjusting for significant baseline predictors. RESULTS Desvenlafaxine 50 mg/d (n = 1207) had significantly greater rates of treatment success for each level of treatment success at 8 weeks compared with placebo (n = 1067). Optimal early improvement thresholds for weeks 2 (20%-30%) and 3 (28%-41%) were highly predictive of all 4 levels of treatment success after adjusting for significant baseline predictors (odds ratios, 0.951-0.960; all P < 0.0001). Negative predictive value of early improvement increased, and positive predictive value decreased, for increasingly stringent definitions of treatment success at week 8. CONCLUSIONS Clinical observations of patients' early response to desvenlafaxine 50 mg/d may have clinical value in predicting treatment success and guiding patient management.

Objectives: Immigrant women living in Canada present with higher rates of prenatal depressive symptomatology than Canadian-born women; however, the associated psychosocial correlates remain understudied. Antenatal depression and stress negatively affect maternal health and infant development, in part through changes in maternal hypothalamic–pituitary–adrenal (HPA) axis activity. We aimed to examine the factors associated with prenatal depressive symptoms, including altered HPA axis function, in an ethnically diverse community sample of Canadian immigrant women. Methods: Seventy-eight pregnant immigrant women were recruited from the community at 19 weeks' gestation and provided information on health, mood, stressful life events (SLEs), and social support. Fifty-seven of these women also provided saliva samples for measurement of the cortisol awakening response and nighttime cortisol levels. Results: Seventeen per cent of the sample had a high level of prenatal depressive symptoms, and these women reported more perceived stress, more somatic symptoms, lower social support, and were less often working or attending school during pregnancy. Controlling for wake time, parity, and region of origin, high levels of prenatal depressive symptoms were associated with elevated nighttime cortisol levels, whereas SLEs were not associated with any measures of HPA axis activity. Conclusions: High levels of prenatal depressive symptoms are common in immigrant women living in Canada, and are associated with identifiable factors. Preliminary evidence suggests a similar pattern of HPA axis activity characterizing depressive symptomatology in this subpopulation as previously seen in clinically depressed patients.

Neurobiological mechanisms underlying the development of major depressive disorder (MDD) may differ depending on age-of-onset. Our aim was to compare patients who differ in age-of-onset, while controlling for illness duration, and number of depressive episodes. By directly comparing early-(EOD) and late-onset (LOD) patients, we examined whether age-of-onset is associated with changes in the extent or spatial pattern of cortical thickness. Cross-sectional comparison of cortical thickness in EOD vs. LOD. Age-of-onset was determined based on self-report, with EOD defined as onset prior to age 25. Reduced cortical thickness in the dorsal-lateral prefrontal cortex (DLPFC), pre- and postcentral gyrus, and the lingual gyrus were found in EOD compared to healthy controls (p

Depression during midlife years may lead to significant sleep disturbances and adversely impact quality of life (QOL). In this report, we examined the effects of treatment with quetiapine extended release (XR), 150–300 mg/day, on sleep and QOL in 23 midlife women with major depressive disorder (MDD). Quetiapine XR improved subjective sleep distress, overall sleep parameters, and sleep-related QOL, ultimately leading to significant improvement in menopause-related QOL. While larger, controlled trials are still awaited, these preliminary results are encouraging and suggest that quetiapine XR may be a useful tool in treating symptomatic midlife women with MDD.

Objective: The purpose of this post hoc analysis was to compare the treatment effect size of eszopiclone 3 mg for insomnia in patients with a diagnosis of primary insomnia and in several of the psychiatric and medical conditions that are most commonly comorbid with insomnia. Method: Data were analyzed from 5 large, multicenter, randomized, double-blind, placebo-controlled studies of adult outpatients of at least 1 month duration published between 2006 and 2009. Diary-derived indices of sleep and daytime functioning and the Insomnia Severity Index were compared for patients with primary insomnia (DSM-IV-TR criteria, n = 828) and for those with insomnia comorbid with major depressive disorder (MDD, DSM-IV-TR criteria, n = 545), generalized anxiety disorder (GAD, DSM-IV-TR criteria, n = 595), perimenopause/postmenopause (Stages of Reproductive Aging Workshop criteria, n = 410), and rheumatoid arthritis (American College of Rheumatology criteria, n = 153). Cohen d effect sizes were calculated for each individual study as the between-treatment difference score divided by the pooled standard deviation. Results: Effect sizes ranged from 0.40 to 0.69 (small–medium) as early as week 1 and were maintained at 0.26–0.63 at week 4 for sleep latency, wake time after sleep onset, and total sleep time. Sleep latency and total sleep time effect sizes increased from week 1 to week 4 in the primary insomnia group. At week 4, effect sizes on all 3 parameters and the Insomnia Severity Index tended to be highest for the primary insomnia patients and tended to be lowest for patients with comorbid GAD and MDD. The effect sizes for daytime functioning were small for all insomnia patient groups. Conclusions: Eszopiclone 3 mg is an effective treatment for insomnia across 5 clinically diverse patient populations; however, magnitude of effect is mediated by underlying comorbidity and their treatments, with largest measures of effect seen in primary insomnia and lowest in MDD and GAD. These consistent results, and the fact that clinical trials were conducted in patients being treated as appropriate for their comorbid clinical conditions, support the results’ real-world generalizability and utility to clinical practice.