Obstet Gynecol. 2006 Dec;108(6):1402-1410

Soares CN, Joffe H, Rubens R, Caron J, Roth T, Cohen L.

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.

J Clin Psychopharmacol. 2006 Aug;26(4):361-6

Wroolie TE, Williams KE, Keller J, Zappert LN, Shelton SD, Kenna HA, Reynolds MF, Rasgon NL.

OBJECTIVE:: This study assessed mood and neuropsychological function in a population of middle-aged women with major depressive disorder treated with escitalopram. METHODS:: Psychometric data measuring severity of depression were collected from 19 women and neuropsychological data were collected from 17 women aged between 45 and 65 years with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnosis of major depression in a study in the Behavioral Neuroendocrinology Program at the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine. All women were treated with escitalopram in an open-label design. Mean age was 55.94 years and mean number of years of education was 16.36 years. Diagnosis of major depressive disorder was assessed with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and mood was evaluated with the 21-item Hamilton Depression Rating Scale (HAM-D) at baseline and at weekly follow-ups for 12 weeks. Cognition was assessed at baseline and 3 months after treatment using a neuropsychological test battery, which included an abbreviated measure of Full Scale Intelligence Quotient, measures of attention and processing speed, verbal and nonverbal memory, executive functioning, and verbal fluency. Self-report data were collected on current menopause status and current hormone therapy use in the postmenopausal women. Paired sample t tests were used to analyze the change in total HAM-D scores and neuropsychological variables. RESULTS:: Statistically significant improvements were found in total HAM-D score, Wechsler Memory Scale III Logical Memory 1st Recall, I, and II scores, Wechsler Memory Scale III Visual Reproduction I scores, and Trail Making Test Part B scores. There was a statistically significant decrease in Controlled Oral Word Association Test FAS scores. CONCLUSIONS:: Treatment of depression with escitalopram in a population of middle-aged women was shown to improve mood and cognitive efficiency in complex attention, short- and long-term recall of contextual information, short-term recall of visual information, and cognitive flexibility; however, it was shown to worsen phonemic fluency.

Menopause. 2006 Jul-Aug;13(4):568-75

Sertraline to treat hot flashes: a randomized controlled, double-blind, crossover trial in a general population.

Gordon PR, Kerwin JP, Boesen KG, Senf J.

From the College of Medicine, University of Arizona, Tucson, AZ.

OBJECTIVE:: To evaluate the effectiveness of a selective serotonin reuptake inhibitor (SSRI) (sertraline) in decreasing hot flashes in a general population of women. DESIGN:: A double-blind, placebo-controlled, crossover trial was conducted in a southwestern urban setting. A total of 102 women aged 40 to 65 who were experiencing hot flashes and not taking any hormone therapy were recruited. After 1 week of baseline hot flash data collection, study participants were randomized to receive placebo or active drug (sertraline 50 mg) for 4 weeks. This intervention was followed by a 1-week washout and cross over to the opposite treatment for 4 weeks. The number and severity of hot flashes were measured. RESULTS:: One hundred two women were enrolled in the study. Five dropped out before providing baseline data. Of the 97 remaining, 52 were randomized to active drug first and 45 to placebo first. Ten dropped out of the study before completing all 10 weeks, leaving 46 in the active drug-first arm and 41 in the placebo-first arm. At baseline, the mean number of hot flashes reported was 45.6 per week (SD = 29.6), ranging from 2 to 148. During the sertraline phase of the study, women experienced five fewer hot flashes per week than they did on the placebo (P = 0.002). The severity of hot flashes was not significantly different; however, the hot flash score (number x average severity) was significantly improved during the sertraline phase. CONCLUSION:: Sertraline reduced the number of hot flashes and improved the hot flash score relative to placebo and may be an acceptable alternative treatment for women experiencing hot flashes.

Arch Gen Psychiatry. 2006 Apr;63(4):385-390

Cohen LS, Soares CN, Vitonis AF, Otto MW, Harlow BL.

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.

Arch Gen Psychiatry. 2006 Apr;63(4):375-382

Freeman EW, Sammel MD, Lin H, Nelson DB.

CONTEXT: Whether depressed mood reported in the transition to menopause by women with no history of depression is associated with menopausal status and changes in reproductive hormones is controversial and lacks scientific information. OBJECTIVES: To identify new onset of depressive symptoms and diagnosed depressive disorders in the menopausal transition and to determine the associations of menopausal status, reproductive hormones, and other risk factors with these cases. DESIGN: A within-woman, longitudinal (8-year) study to identify risk factors of depressed mood. SETTING: A subset of a randomly identified, population-based cohort. PARTICIPANTS: Premenopausal women with no history of depression at cohort enrollment. MAIN OUTCOME MEASURES: The Center for Epidemiological Studies of Depression scale (CES-D) was used to assess depressive symptoms, and the Primary Care Evaluation of Mental Disorders (PRIME-MD) was used to identify clinical diagnoses of depressive disorders. RESULTS: High CES-D scores (>/=16) were more than 4 times more likely to occur during a woman's menopausal transition compared with when she was premenopausal (odds ratio, 4.29; 95% confidence interval, 2.39-7.72; P<.001). Within-woman change in menopausal status, increased levels of follicle-stimulating hormone and luteinizing hormone, and increased variability of estradiol, follicle-stimulating hormone, and luteinizing hormone around the woman's own mean levels were each significantly associated with high CES-D scores after adjusting for smoking, body mass index, premenstrual syndrome, hot flashes, poor sleep, health status, employment, and marital status. A diagnosis of depressive disorder was 2(1/2) times more likely to occur in the menopausal transition compared with when the woman was premenopausal (odds ratio, 2.50; 95% confidence interval, 1.25-5.02; P=.01); the hormone measures were also significantly associated with this outcome. CONCLUSION: Transition to menopause and its changing hormonal milieu are strongly associated with new onset of depressed mood among women with no history of depression.

Fertil Steril. 2006 Apr;85(4):972-8

Casini ML, Marelli G, Papaleo E, Ferrari A, D'Ambrosio F, Unfer V.

OBJECTIVE: To investigate the effects of soy isoflavones on mood and cognitive function in postmenopausal women. DESIGN: Randomized, double-blind, cross-over, placebo-controlled trial. SETTING: University Hospital, Milan, Italy; A.G.UN.CO. Obstetrics and Gynaecology Centre, Rome, Italy. PATIENT(S): Seventy-eight postmenopausal women. INTERVENTION(S): We administered 60 mg/day isoflavones or placebo for 6 months. After a washout period of 1 month, the patients who had been treated with phytoestrogens received placebo, and those who previously received placebo were administered phytoestrogens (for 6 months). MAIN OUTCOME MEASURE(S): Cognitive performance and mood were assessed by a battery of tests at the end of each treatment period. At the end of the study, the patients were also asked whether they preferred the first or second treatment. RESULT(S): The 17 scores on cognitive performance test and the 6 for mood assessments 6 showed an advantage for the treatment with phytoestrogens. Similarly, of the 8 visual analogue scales used to indicate mood, 7 improved significantly after the treatment with phytoestrogens. Moreover, 49 patients preferred phytoestrogens, 9 placebo, and 18 had no preference. The preference was not related to the order of treatment. CONCLUSION(S): These results suggest that isoflavones may have positive effects on postmenopausal women improving cognitive performance and mood.

J Psychiatry Neurosci2006;31(2):122-31.

Sidney H. Kennedy, MD; Henning F. Andersen, MSc; Raymond W. Lam, MD

Objective: Escitalopram is the most selective of the selective serotonin reuptake inhibitor (SSRI) antidepressants. Previous studies have suggested that escitalopram is superior to citalopram in efficacy. We conducted a meta-analysis of studies in which escitalopram was compared with other antidepressants to assess the relative efficacy of these agents. Methods: Data from all randomized, double-blind studies in major depression in which escitalopram was compared with active controls (citalopram, fluoxetine, paroxetine, sertraline and venlafaxine XR [extended release]) were pooled. The 10 studies were conducted in both specialist settings and general practice. Patients met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), for major depressive disorder and were at least 18 years old. In all but 2 studies, patients were required to have a score of 22 or more on the Montgomery-Åsberg Depression Rating Scale (MADRS). The primary outcome measure was the estimated difference in treatment effect in MADRS total score at the end of the study. Secondary outcome measures were the response to treatment (defined as a = 50% reduction in baseline MADRS total score) and remission rate (defined as MADRS total score = 12 at end of study). Results: A total of 2687 patients were included in the analyses (escitalopram n= 1345, conventional SSRIs n= 1102, venlafaxine XR n= 240). Escitalopram was superior to all comparators in overall treatment effect, with an estimated difference in treatment effect of 1.07 points (95% confidence interval [CI] 0.42-1.73, p < 0.01), and in response (odds ratio [OR] 1.29, 95% CI 1.07-1.56, p < 0.01) and remission (OR 1.21, 95% CI 1.01-1.46, p< 0.05) rates. In analysis by medication class, escitalopram was significantly superior to the SSRIs and comparable to venlafaxine, although the overall results do not necessarily reflect a significant difference between escitalopram and individual SSRIs. These results were similar in the severely depressed population (patients with baseline MADRS = 30). The withdrawal rate due to adverse events was 6.7% for escitalopram compared with 9.1% for the comparators ( p < 0.05).  Conclusions: In this meta-analysis, escitalopram showed significant superiority in efficacy compared with the active controls.

Psychopharmacology (Berl). 2006 May 25; [Epub ahead of print]

Andreen L, Sundstrom-Poromaa I, Bixo M, Nyberg S, Backstrom T.

RATIONALE: Allopregnanolone effects on mood in postmenopausal women are unclear thus far. OBJECTIVES: Allopregnanolone is a neuroactive steroid with contradictory effects. Anaesthetic, sedative, and anxiolytic as well as aggressive and anxiogenic properties have been reported. The aim of this study is to compare severity of negative mood between women receiving different serum allopregnanolone concentrations during progesterone treatment. MATERIALS AND METHODS: A randomized, placebo-controlled, double-blind, crossover study of postmenopausal women (n=43) treated with 2 mg estradiol daily during four treatment cycles. Oral micronized progesterone at 30, 60, and 200 mg/day, and placebo were added sequentially to each cycle. Participants kept daily symptom ratings using a validated rating scale. Blood samples for progesterone and allopregnanolone analyses were collected during each treatment cycle. RESULTS: During progesterone treatment, women had significantly higher negative mood scores when allopregnanolone serum concentration was in the range of 1.5-2 nmol/l compared to lower and higher concentrations. In addition, women displayed a significant increase in negative mood during the progesterone treatment period, compared to the estradiol-only period when 30 mg progesterone daily was used. On the other hand, treatment with higher doses of progesterone had no influence on negative mood. CONCLUSIONS: Mood effects during progesterone treatment seem to be related to allopregnanolone concentration, and a bimodal association between allopregnanolone and adverse mood is evident.

IRS PARA TRATAR BOCHORNOS, TURNO DE LA SERTRALINA.

En Menopause de Julio de 2006 se publica otra experiencia de tratamiento de bochornos con inhibidores de recaptación de serotonina (IRS). Esta vez es un diseño aleatorizado de sertralina contra placebo que muestra una pequeña pero significativa ventaja de sertralina sobre placebo: la frecuencia de bochornos baja en promedio de 45 a 40 por semana sin afectar la severidad. Estos resultados son similares a los reportados con venlafaxina y algo superiores a los de fluoxetina y citalopram. También ha mostrado un efecto la gabapentina, un antiepiléptico antineurítico que también tiene efectos sobre la recaptación de serotonina. Sin embargo, ninguno de estos tratamientos supera a los estrógenos para este propósito y los estudios comparados muestran que los estrógenos son unas cinco veces más eficaces que los IRS o más.

ESCITALOPRAM ES TAN EFECTIVO EN LA POSMENOPAUSIA PARA TRATAR DEPRESIÓN COMO A OTRAS EDADES.

Es lo que se deduce de un pequeño estudio que evalúa no solamente la escala de Hamilton que enfatiza los aspectos emocionales de la depresión, también las habilidades cognitivas, que son fundamentales para la mejoría de la adaptabilidad de la paciente.