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Biomedical subjects

Claudio N Soares

Publications and source records attributed to Claudio N Soares.

At least 19 recordsLinked to original sources

Exploring sex differences in endocannabinoid system biomarkers and their relationship with antidepressant treatment outcomes in major depressive disorder: a CAN-BIND 1 secondary analysis.

BACKGROUND: Sex differences in major depressive disorder (MDD) are well documented, but it remains unclear whether sex-related variation in peripheral endocannabinoid system (ECS)-related biomarkers is detectable in MDD. OBJECTIVES: To examine baseline sex differences in ECS-related mRNA expression, DNA methylation, and single nucleotide polymorphisms (SNPs) in MDD, and associations between baseline ECS markers and antidepressant outcomes in sex-stratified analyses. METHODS: Among 178 participants with MDD from CAN-BIND-1, all received escitalopram for 8 weeks; non-responders then received adjunctive aripiprazole from Weeks 8-16.Response was defined as ≥ 50% reduction in MADRS score, and remission as MADRS ≤ 10. ANCOVAs examined baseline sex differences and sex-stratified biomarker associations with percent MADRS reduction at Weeks 8 and 16, as well as categorical response and remission outcomes. Covariates included site, baseline MADRS, age, and ethnicity. False discovery rate correction was applied. RESULTS: Baseline sex differences in methylation were observed for CACNA1H, GABRB2, MAGL, and GABRR2, though none survived correction. No baseline sex differences in mRNA expression or SNPs were detected after correction. Lower baseline DAGLA mRNA in males was associated with greater Week 8 symptom improvement (FDR corrected). This association was not observed in females. No associations with response or remission at Weeks 8 or 16 survived correction. IMPLICATIONS: Baseline sex differences in peripheral ECS-related markers were not detected in this sample. Larger studies are needed to verify whether ECS-related biomarkers, particularly DAGLA, contribute to antidepressant outcomes in a sex-specific manner.

Humans↗

Risk for new onset of depression during the menopausal transition: the Harvard study of moods and cycles.

CONTEXT: Transition to menopause has long been considered a period of increased risk for depressive symptoms. However, it is unclear whether this period is one of increased risk for major depressive disorder, particularly for women who have not had a previous episode of depression. OBJECTIVE: To examine the association between the menopausal transition and onset of first lifetime episode of depression among women with no history of mood disturbance. DESIGN: Longitudinal, prospective cohort study. SETTING: A population-based cross-sectional sample. PARTICIPANTS: Premenopausal women, 36 to 45 years of age, with no lifetime diagnosis of major depression (N = 460), residing in 7 Boston, Mass, metropolitan area communities. Main Outcome Measure Incidence of new onset of depression based on structured clinical interviews, Center for Epidemiologic Studies Depression Scale scores, and an operational construct for depression. RESULTS: Premenopausal women with no lifetime history of major depression who entered the perimenopause were twice as likely to develop significant depressive symptoms as women who remained premenopausal, after adjustment for age at study enrollment and history of negative life events. The increased risk for depression was somewhat greater in women with self-reported vasomotor symptoms. CONCLUSIONS: The current study suggests that within a similarly aged population of women with no lifetime history of depression, those who enter the menopausal transition earlier have a significant risk for first onset of depression. Further studies are needed to determine more definitively whether other factors, such as the presence of vasomotor symptoms, use of hormone therapy, and the occurrence of adverse life events, independently modify this risk. Physical symptoms associated with the menopausal transition and mood changes seen during this period may affect many women as they age and may lead to a significant burden of illness.

Adult↗

Sleep disorders in women: clinical evidence and treatment strategies.

Sleep disorders are more prevalent in women than in men. Sex hormones modulate sleep-wake behaviors and mood and may contribute to heightened risk across the life cycle of women. Sleep disorders may have a unique expression in women, emerging throughout their reproductive life cycle. These conditions require careful treatment strategy to manage medical, hormonal, and behavioral contributing factors to poor sleep efficiency and impaired quality of life. This review focuses on clinical evidence for sleep disorders in women and discusses existing evidence of risk factors and treatment options for insomnia and sleep-disordered breathing in women.

Adult↗

Eszopiclone in patients with insomnia during perimenopause and early postmenopause: a randomized controlled trial.

OBJECTIVE: To evaluate eszopiclone 3 mg for treatment of insomnia in perimenopausal and early postmenopausal women, as well as the impact of insomnia treatment on mood, menopause-related symptoms, and quality of life. METHODS: This was a double-blind, placebo-controlled study with 410 women (aged 40-60; perimenopausal or early postmenopausal) who reported insomnia defined as sleep latency of at least 45 minutes and total sleep time less than or equal to 6 hours per night for at least 3 nights per week over the previous month. Patients were randomly assigned to eszopiclone 3 mg or placebo nightly for 4 weeks. Sleep data were collected once a day. Physician global assessments of menopause, menopause-specific questionnaire, Greene Climacteric Scale, the Montgomery Asberg Depression Rating Scale, and the Sheehan Disability Scale were collected at baseline and end of treatment. RESULTS: Patients receiving eszopiclone reported improvements in sleep induction, sleep maintenance, sleep duration, sleep quality, and next-day functioning relative to placebo (P<.05). Patients receiving eszopiclone reported fewer total awakenings and awakenings due to hot flushes (P<.05). Eszopiclone use led to greater improvement in Montgomery Asberg Depression Rating Scale scores (P<.05) and physician global assessments of menopause scores (P<.001); total Greene Climacteric Scale score and the vasomotor and psychological sub-scores (P<.05); vasomotor and physical domains of the menopause-specific questionnaire (P<.05); and family life/home domain of the Sheehan Disability Scale (P<.05). CONCLUSION: In this study, eszopiclone provided significant improvements in sleep and positively impacted mood, quality of life, and menopause-related symptoms in perimenopausal and early postmenopausal women with insomnia. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov www.clinicaltrials.gov NCT00366093 LEVEL OF EVIDENCE: I.

Affect↗

Women and reproductive-related trauma.

Women are at higher risk for developing posttraumatic stress disorder (PTSD) than men, leading to significant psychosocial burden and healthcare-related costs. Research has shown an association between the negative impact of traumatic experiences and the reproductive life cycle in women. Pregnant women with a history of abuse/trauma frequently report intrusive reemergence of symptoms. Women who experience miscarriage may present with even higher prevalence rates of PTSD symptoms. Both psychologic and physiologic factors are believed to be relevant to the development of peripartum posttraumatic stress symptoms. Much less is known, however, about treatment. A case series of patients who presented with PTSD symptoms in the context of reproductive-related traumatic events (e.g., miscarriage, stillbirth) or who experienced reemergence of symptoms during pregnancy is presented, including treatment strategies.

Abortion, Spontaneous↗

Diagnosis and management of mood disorders during the menopausal transition.

Recent census data indicate that, in the United States, an increasing number of women--almost 1.5 million each year--are reaching menopause. The menopausal transition is marked by intense hormonal fluctuations, and may be accompanied by vasomotor complaints, sleep disturbances, changes in sexual function, and increased risk for osteoporosis and cardiovascular disease. In addition, there is evidence of increased risk for developing depression, even among women who never experienced depressive symptoms before. Thus depression during the perimenopause may have a substantial impact on personal, family, and professional spheres of life. A challenge to clinicians and health professionals lies in the identification of the most tolerable treatments to manage depression and improve quality of life in an aging population. Any treatment strategy should take into account not only the spectrum of side effects that may complicate treatment but also other menopause-related factors (e.g., vasomotor symptoms, psychosocial stressors) that may modulate risk for the development of mood disturbance. This article reviews the current literature on the prevalence and risk factors associated with depression during the menopausal transition. The benefits and risks of using hormonal and nonhormonal strategies for the management of depression and other menopause-related somatic symptoms are critically reviewed.

Antidepressive Agents↗

[Trauma & the reproductive lifecycle in women].

Women are at significantly higher risk for developing post-traumatic stress disorder (PTSD) than men, resulting in increased psychosocial burden and healthcare related costs. Recent research has shown complex interactions between the impact of traumatic experiences, and the reproductive lifecycle in women. For example, women suffering from premenstrual dysphoric disorder (PMDD) who also report a history of sexual or physical abuse are more likely to present with different neuroendocrine reactivity to stressors, when compared to premenstrual dysphoric disorder subjects without prior history of trauma or abuse or non-premenstrual dysphoric disorder subjects. In addition, women with a history of abuse or trauma may experience re-emergence of symptoms during pregnancy. Lastly, females who experience miscarriage may present with even higher prevalence rates of post-traumatic stress disorder symptoms. In this manuscript we examine the existing data on gender differences in post-traumatic stress disorder, with particular focus on psychological and physiological factors that might be relevant to the development of symptoms after exposure to traumatic events associated with the reproductive life cycle. Current options available for the treatment of such symptoms, including group and counselling therapies and debriefing are critically reviewed.

Abortion, Spontaneous↗

Bupropion SR for the treatment of postpartum depression: a pilot study.

Despite the prevalence of postpartum depression, few studies have assessed the efficacy of antidepressants for the treatment of this disorder. Failure to treat postpartum depression (PPD) places the woman at risk for chronic depression and may have adverse effects on child wellbeing and development. Eight female outpatients aged 18-45 yr were enrolled in an 8-wk open-label trial of bupropion SR for PPD. All patients met DSM-IV criteria for major depression with onset within 3 months of delivery and scored 17 or greater on the Hamilton Depression Rating Scale (HAMD) at baseline. Those with onset of depressive symptoms during pregnancy, psychotic symptoms, or significant medical illness were excluded. Median scores on the HAMD declined from 20.5 (range 15-38) at baseline to 10.0 (range 1-20) at end-point (p<0.05, Wilcoxon signed-ranks test; LOCF). Six out of the eight subjects demonstrated a > or =50% decrease in HAMD scores from baseline; three subjects achieved remission (HAMD score of < or =7) at week 8. Median final dosage of bupropion SR was 262.5 (range 37.5-300). Bupropion SR was well tolerated, and no subjects discontinued treatment as a result of medication side-effects. Bupropion SR represents an effective and well-tolerated antidepressant for the treatment of PPD.

Adolescent↗

Treatment of menopause-related mood disturbances.

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.

Estrogen Replacement Therapy↗

Antidepressant response and well-being in pre-, peri- and postmenopausal women with major depressive disorder treated with fluoxetine.

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 or=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.

Adult↗

Menopause and mood.

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Antidepressive Agents↗

Efficacy and tolerability of premenstrual use of venlafaxine (flexible dose) in the treatment of premenstrual dysphoric disorder.

The objective of this study was to examine the efficacy and tolerability of intermittent dosing of venlafaxine for the treatment of premenstrual dysphoric disorder. One hundred and twenty-four women aged 18 to 45 years, with regular menstrual cycles and who reported significant premenstrual symptoms, were assessed prospectively to confirm their diagnosis of premenstrual dysphoric disorder. Twenty subjects with confirmed premenstrual dysphoric disorder entered a single-blind, placebo phase (1 cycle). Placebo nonresponders (n = 12) received 2 cycles of intermittent (premenstrual) treatment with venlafaxine (75 to 112.5 mg/d). Subjects initiated treatment 14 days before the anticipated onset of menses and discontinued it on the second day of bleeding. Doses could be adjusted after cycle 1 based on subjects' response and tolerability. Response to treatment was assessed based on changes in the Daily Rating Severity of Problems and Premenstrual Tension Syndrome Questionnaire scores from baseline (before the placebo cycle), as well as Clinical Global Impression-Severity scores. Discontinuation symptoms were assessed between treatment cycles, using the Discontinuation-Emergent Signs and Symptoms questionnaire. Eleven subjects concluded 2 cycles of intermittent dosing with venlafaxine. Nine subjects (81.8%) showed satisfactory response based on Clinical Global Impression of < or = 2. Changes in Daily Rating Severity of Problems scores and subscores (depression, physical symptoms, and anger) and in Premenstrual Tension Syndrome Questionnaire scores were significant (P < 0.05 for all comparisons, Wilcoxon tests). Intermittent treatment was well tolerated. This preliminary report suggests that premenstrual use of venlafaxine is an efficacious and well-tolerated treatment for premenstrual dysphoric disorder.

Adult↗

Depression and its influence on reproductive endocrine and menstrual cycle markers associated with perimenopause: the Harvard Study of Moods and Cycles.

BACKGROUND: Few studies have determined the impact of a lifetime history of major depression on an early transition to menopause. METHODS: Reproductive and psychiatric interviews and early follicular-phase blood specimens were obtained at study enrollment and every 6 months during 36 months of follow-up from 332 women with and 644 women without a history of major depression, 36 to 45 years of age. We used menstrual cycle markers to determine inception of perimenopause, defined as time from study enrollment to a follow-up interview with: (1) 7-day or more change in menstrual cycle length; (2) a change in menstrual flow amount or duration; or (3) amenorrhea lasting at least 3 months. RESULTS: Women with a history of depression had 1.2 times the rate of perimenopause of women with no such history (95% confidence interval, 0.9-1.6). Compared with nondepressed women, depressed women with more pronounced depressive symptoms at study enrollment (Hamilton Rating Scale for Depression scores >8) had twice the risk of an earlier perimenopausal transition. Among the women with greater depressive symptoms (Hamilton scores >8), those who also reported use of antidepressants had nearly 3 times the risk of an earlier perimenopausal transition (hazard ratio, 2.7; 95% confidence interval, 1.5-4.8) of nondepressed women. Women with a lifetime history of depression also had higher follicle-stimulating hormone and luteinizing hormone levels and lower estradiol levels at study enrollment and during the follow-up period after adjustment for covariates. CONCLUSION: A lifetime history of major depression may be associated with an early decline in ovarian function.

Adult↗

Assessment and treatment of hot flushes and menopausal mood disturbance.

More than 1 million women are expected to reach menopause each year, many of whom will experience hot flushes and other neuropsychological symptoms that may diminish their quality of life. Hot flushes are the core symptoms that reflect the brain's response to the changing hormonal milieu of the menopause transition, particularly to the rapidly fluctuating and falling levels of estradiol. The physical symptoms of hot flushes and the associated changes in sleep, mood, and cognition will lead many women to seek medical care. It is critical to understand the interrelationship of hot flushes and other neuropsychological symptoms of the menopause transition so that treatment priorities can be established. For example, if sleep disruption explains most daytime neuropsychological problems in women with hot flushes, treating insomnia should be considered a priority. Alternatively, mood, cognition, and quality of life may be disturbed independent of sleep problems. In such a situation, each symptom should be evaluated separately from any assessment of sleep. As recent data from the WHI establish the risks of long-term HRT use, concern about using HRT, even as a short-term intervention, has increased substantially. Although HRT remains the first-line treatment for hot flushes, the WHI findings have drawn attention to nonhormonal treatments of hot flushes and other menopausal symptoms. Growing evidence to support the efficacy of serotonergic antidepressants and other psychoactive medications in the treatment for hot flushes suggests that nonhormonal interventions will prove important alternatives to HRT. As further evidence of the benefits of psychoactive medications for menopausal symptoms is established, the choice between using hormonal and nonhormonal therapies for management of menopausal symptoms will continue to evolve.

Acetates↗

Short-term use of estradiol for depression in perimenopausal and postmenopausal women: a preliminary report.

OBJECTIVE: The authors examined the effect of a 4-week course of estrogen therapy on depression in perimenopausal and postmenopausal women. METHOD: Twenty-two depressed women who were either perimenopausal (N=10) or postmenopausal (N=12) received open-label treatment with transdermal 17beta-estradiol (100 micro g/day) for 4 weeks. The Montgomery-Asberg Depression Rating Scale and the Beck Depression Inventory were used to assess depressive symptoms, the Greene Climacteric Scale was used to assess menopause-related symptoms, and the Clinical Global Impression (CGI) was used to assess global clinical improvement in these women at baseline and after treatment. Remission of depression was defined as a score <10 on the Montgomery-Asberg Depression Rating Scale and a score </=2 on the CGI at week 4. RESULTS: Remission of depression was noted in eight of the 20 women who completed the study; two of these women were postmenopausal, and six were perimenopausal. Antidepressant response was not associated with severity or subtypes of depression at study entry or with concomitant improvement in menopause-related symptoms. CONCLUSIONS: Some perimenopausal women with depression may benefit from short-term use of estrogen therapy, and its role for postmenopausal depressed women warrants further investigation. Antidepressant benefit associated with estrogen therapy may be independent of improvement in physical symptoms.

Administration, Cutaneous↗

Effect of reproductive hormones and selective estrogen receptor modulators on mood during menopause.

Periods of intense hormonal fluctuations have been associated with heightened prevalence and exacerbation of underlying psychiatric illness, particularly the occurrence of premenstrual dysphoria, puerperal depression and depressive symptoms during perimenopause. It has been speculated that sex steroids such as estrogens, progestogens, testosterone and dehydroepiandrosterone (DHEA) exert a significant modulation of brain functioning, possibly through interactions with various neurotransmitter systems. It is therefore intuitive that abrupt alterations of these hormones would interfere with mood and behaviour. On the other hand, accumulating data suggest that hormonal interventions may also promote relief or even remission of depressive symptoms, as already demonstrated in studies with patients experiencing postpartum depression and perimenopausal depressive disorders. The extent to which perimenopause, alone, may increase the risk for depression is unclear. However, existing data strongly suggest that some women are particularly vulnerable to developing significant physical and psychological disturbances when entering perimenopause. This article reviews the effect of sex hormones and selective estrogen receptor modulators (SERMs) on mood among peri- and postmenopausal women. There are preliminary, though promising, data on the use of estradiol (particularly transdermal estradiol) to alleviate depression during perimenopause, use of a combination of estrogens and selective serotonin reuptake inhibitors for depression during the postmenopausal period, and the use of testosterone to improve psychological well-being and increase libido among women with induced menopause. Further studies would help to better delineate the usage of hormones as an antidepressant strategy (monotherapy or augmenting treatment) for peri- and postmenopausal women. A brief review of some nonhormonal interventions for the treatment of menopause-related symptoms that may significantly affect a woman's quality of life is also presented. There are some preliminary data suggesting the efficacy of antidepressants for the treatment of hot flushes; existing data on diet supplements and herbal products have shown more mixed results.

Affect↗

Efficacy of citalopram as a monotherapy or as an adjunctive treatment to estrogen therapy for perimenopausal and postmenopausal women with depression and vasomotor symptoms.

BACKGROUND: Women frequently report depressive and vasomotor symptoms during the menopausal transition. Hormone therapy has been shown to improve some of these symptoms, although its safety as a long-term treatment has been questioned. It is still unclear whether the use of antidepressants alone may alleviate menopause-related mood and vasomotor symptoms or enhance the response observed with short-term use of estrogen therapy. METHOD: Perimenopausal and postmenopausal women with depressive disorders (DSM-IV criteria) and menopause-related symptoms received treatment with 20 to 60 mg/day of citalopram alone (N = 22) or adjunctive to estrogen therapy (N = 13). Adjunctive treatment was offered to subjects who had failed to show remission of depression after 4 weeks with estrogen therapy (estradiol [E(2)]) alone. Depressive symptoms, menopause-related symptoms, and global clinical improvement were assessed at baseline and at endpoint of adjunctive treatment (8 weeks) or citalopram monotherapy (12 weeks). Remission of depression was defined as a score of < 10 on the Montgomery-Asberg Depression Rating Scale and a score of < or = 2 on the Clinical Global Impressions scale at endpoint. Data were collected from November 2000 to February 2002. RESULTS: Twelve women (92.3%) concluded the 8-week adjunctive treatment; 11 subjects (91.6%) achieved full remission of depression. Symptoms that had persisted after an initial 4-week treatment with E(2) alone (e.g., tension, anxiousness, tiredness, and difficulty in concentrating) improved significantly (p <.05). Fifteen subjects concluded the treatment with citalopram monotherapy; 13 subjects (86.6%) showed full remission of depression. Anxiety and other somatic complaints had significant improvement (p <.05), while there was a trend toward improvement in vasomotor symptoms in those receiving monotherapy (p =.06). CONCLUSION: Citalopram alone is an efficacious treatment for perimenopausal and postmenopausal women with depression. Citalopram also appears to be efficacious as an adjunctive treatment for depressed subjects who remain symptomatic after treatment with E(2) (i.e., E(2) nonremitters). The role of citalopram monotherapy for the management of vasomotor symptoms warrants further investigation.

Adult↗