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Insomnia Pharmacotherapy: a Review of Current Treatment Options for Insomnia in Menopause

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Abstract

Purpose of Review Women are living longer and spending nearly one third of their lives in the climacteric period with the consequences of hypoestrogenism. Insomnia is the major clinical manifestation of this period. The aim of this chapter is to sum up current treatment options for menopausal insomnia and related symptoms. The paper summarizes some main treatment alternatives to treatment of insomnia in women, especially during the menopausal transition and postmenopause: What are the alternatives for treatment of insomnia in this population? What is the level of evidence of each of them? Recent Findings Previous studies have shown that the studies use very heterogeneous groups of women with different types of insomnia. This lack of standardized methods makes it difficult to identify the best therapeutic option for insomnia after menopause. However, this does not mean that it is impossible to define the best treatment intervention. Summary The findings from each therapy were categorized according to the level of evidence, based on the scientific knowledge. We highlight the importance of the patient being evaluated by a multidisciplinary team, and of taking a broad approach which considers both the pharmacological and biopsychosocial context to deliver the most effective treatment.
INSOMNIA AND PHARMACOTHERAPY (H ATTARIAN AND M KAY-STACEY, SECTION EDITORS)
Insomnia Pharmacotherapy: a Review of Current Treatment
Options for Insomnia in Menopause
Helena Hachul
1,2,3
&Daniel Ninello Polesel
2
Published online: 9 September 2017
#Springer International Publishing AG 2017
Abstract
Purpose of Review Women are living longer and spending
nearly one third of their lives in the climacteric period with
the consequences of hypoestrogenism. Insomnia is the major
clinical manifestation of this period. The aim of this chapter is
to sum up current treatment options for menopausal insomnia
and related symptoms. The paper summarizes some main
treatment alternatives to treatment of insomnia in women,
especially during the menopausal transition and postmeno-
pause: What are the alternatives for treatment of insomnia in
this population? What is the level of evidence of each of them?
Recent Findings Previous studies have shown that the studies
use very heterogeneous groups of women with different types
of insomnia. This lack of standardized methods makes it dif-
ficult to identify the best therapeutic option for insomnia after
menopause. However, this does not mean that it is impossible
to define the best treatment intervention.
Summary The findings from each therapy were categorized
according to the level of evidence, based on the scientific
knowledge. We highlight the importance of the patient being
evaluated by a multidisciplinary team, and of taking a broad
approach which considers both the pharmacological and
biopsychosocial context to deliver the most effective
treatment.
Keywords Sleep .Insomnia .Menopause .Menopausal
transition .Hormonaltherapy .Complementaryandalternative
medicine
Introduction
Menopause
Menopause iscommonly defined as the end of womensmen-
strual cycles, after which women suffer the consequences of
hypoestrogenism. According to the World Health
Organization [1], the menopause transition represents the
change from the reproductive to the nonreproductive life
stage. The diagnosis of menopause is confirmed after 12 con-
secutive months of amenorrhea (lack of menstruation).
Clinical Manifestations
Women in menopausal transition have irregular menstrual cy-
cles until the start of amenorrhea, after which the postmeno-
pausal period begins. During this stage, women become af-
fected by hypoestrogenism that leads to short- and long-term
physiological changes.
Manifestations of the early postmenopause include the
presence of vasomotor symptoms (with hot flashes and in-
creased sweating), which occur in nearly 70% of women [2],
insomnia, increased irritability, anxiety and depression, mem-
ory problems, and decreased libido. The late post-menopause
manifestations resulting from longer term absence of estrogen
include increases in low-density lipoprotein, osteopenia
This article is part of the Topical Collection on Insomnia and
Pharmacotherapy
*Helena Hachul
helenahachul@gmail.com
1
Departamento de Ginecologia, Head of the Womens Sleep Division,
Universidade Federal de São Paulo, Rua Napoleão de Barros 925,
São Paulo, SP 04021-002, Brazil
2
Departamento de Psicobiologia, Universidade Federal de São Paulo,
São Paulo, Brazil
3
Departamento de Ginecologia, Casa de Saúde Santa Marcelina, São
Paulo, Brazil
Curr Sleep Medicine Rep (2017) 3:299305
DOI 10.1007/s40675-017-0090-3
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... Women with sleep disorders should be offered CBT, which is considered the gold standard for the treatment of chronic insomnia (Hachul & Polesel, 2017). Several meta-analyses have shown the effectiveness of CBT for treatment of insomnia (Murtagh & Greenwood, 1995;M. ...
... When pharmacologic interventions are indicated, management of insomnia may include treatment of vasomotor symptoms with hormone therapy, as well as antidepressants and anticonvulsants (Hachul & Polesel, 2017). Sedatives and hypnotics may be prescribed but should be administered with caution because women may experience difficulties with tolerance, withdrawal, and dependence, as well as rebound insomnia with short-term use (Hall, Kline, & Nowakowski, 2015). ...
... Sedatives and hypnotics may be prescribed but should be administered with caution because women may experience difficulties with tolerance, withdrawal, and dependence, as well as rebound insomnia with short-term use (Hall, Kline, & Nowakowski, 2015). Although the evidence on the use of herbal and nutritional supplements for the treatment of insomnia is scant and generally of poor quality, several studies have reported positive benefit for insomnia and menopausal symptoms with the use of isoflavones, valerian root (Hachul et al., 2011;Hachul & Polesel, 2017;Kohama & Negami, 2013;Mucci et al., 2006;Sarris & Byrne, 2011;Taavoni, Ekbatani, Kashaniyan, & Haghani, 2011), and Phyto Female Complex (SupHerb, n.d.). Nutritional and herbal supplements may be beneficial to women in conjunction with conventional therapies. ...
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Poor sleep is frequently reported by women during the menopausal transition period. Difficulties with sleep can affect women’s physical and emotional health as well as their overall quality of life. Investigators have found that there is a correlation between a woman’s menopausal history and poor sleep; however, there are differences within each menopausal stage. In this short review, we examine a recent secondary analysis study of quality of sleep and risk factors for poor sleep among women ages 45 to 54 years.
... Additionally, menopausal hormone therapy (HT) is effective for sleep disorders in menopausal women (7). However, results based on several clinical studies investigating the effects of HT on insomnia in menopause are inconsistent (13), and numerous factors are involved in this treatment process, including the range of treatment protocols, dosages, and formulations (14). More importantly, a recent meta-analysis involving a search of 424 defined articles, from which 42 trials, showed that only menopausal women with VMS have an improvement in the quality of life with HT (15). ...
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Full-text available
Insomnia, which is associated with menopausal depression, is a common symptom of menopause. Both symptoms have a common etiology, and can affect each other significantly. Pharmacological interventions, including hypnotics and antidepressants, and non-pharmacological therapies are generally administered in clinical practice for insomnia treatment. As another menopausal disorder, osteoporosis is described as a disease of low bone mineral density (BMD), affecting nearly 200 million women worldwide. Postmenopausal osteoporosis is common among middle-aged women. Since postmenopausal osteoporosismainly results fromlow estrogen levels,menopausal hormone therapy (HT) is considered the first-line option for the prevention of osteoporosis during themenopausal period. However, almost no study has evaluated novel treatments for the combined prevention of insomnia, depression, and osteoporosis. Hence, it is necessary to develop new multi-target strategies for the treatment of these disorders to improve the quality of life during this vulnerable period. Melatonin is the major regulator of sleep, and it has been suggested to be safe and effective for bone loss therapy by MT-2 receptor activity. As a result, we hypothesize that agomelatine, an MT-1 and MT-2 receptor agonist and 5-HT2C receptor antagonist, holds promise in the combined treatment of insomnia, depression, and osteoporosis in middle-aged women during menopause.
Chapter
Menopause is a period in a woman’s life that starts from a year after the date of the last menstrual cycle. It can only be confirmed after 12 consecutive months of amenorrhea, associated with changes in luteinizing hormone and follicle-stimulating hormone levels. Global life expectancy has increased and now women spend nearly one third of their lives in the climacteric period, and therefore experience the consequences of hypoestrogenism for longer than before. The hypoestrogenism, resulting from ovarian failure promotes a series of negative consequences in relation to women’s health, like insomnia, anxiety, irritability, hot flashes, sleep-disordered breathing, qualitative alterations in the skin and hair. In addition, there is a modification in fat distribution, with more abdominal after menopause. Vasomotor symptoms, as hot flashes and excessive sweating, which affect and impair sleep quality, are frequently associated with anxiety, irritability and depressive symptoms. Some evidence suggests that there is a bidirectional interaction between psychological distress and decreased estrogen levels. Hormonal therapy can be an effective treatment; however, the potential side effects of hormone therapy (especially thromboembolic events) must be taken in account before it is prescribed. In older women, the risks associated with oral hormone therapy exceed the benefits. Cognitive-behavioral therapy for insomnia has been shown to be the main non-pharmacological treatment, particularly for chronic insomnia. There is strong evidence that multidisciplinary teams can provide an individualized evaluation of the patient as a whole. The best therapeutic approach is a holistic one taking into consideration both the body and the mind and putting the therapy in both pharmacological and biopsychological contexts in order to promote better health and a better quality of life.
Article
Full-text available
Purpose of Review Over the past decade, digital solutions have been developed to support the dissemination of Cognitive Behavioral Therapy (CBT). In this paper, we review the evidence for and implications of digital CBT (dCBT) for insomnia. Recent Findings We propose three categories of dCBT, which differ in the amount of clinician time needed, level of automatization, costs, and scalability: dCBT as support, guided dCBT, and fully automated dCBT. Consistent evidence has been published on the effectiveness of dCBT to address insomnia disorder, in a variety of populations, with effects extending into well-being. Important gaps in the literature are identified around moderators and mediators of dCBT, cost-effectiveness, and the implementation of dCBT. Summary The evidence base for dCBT is rapidly developing and already suggests that dCBT for insomnia is effective. However, further science and digital innovation is required to realize the full potential of dCBT and address important clinical questions.
Article
Objective Despite cautions by professional associations, benzodiazepines (BZD) and Z hypnotics (BZD/Z) are widely prescribed to older adults who are particularly susceptible to insomnia and anxiety, but who are also more sensitive to drugs adverse events. In this study, we assessed the prescription of BZD/Z drugs in a sample of older adults (≥65) who presented for emergency care after a fall. Methods We collected the type, number and dose of BZD/Z drugs prescribed and explored gender differences in the prescription. Results BZD/Z drugs were prescribed to 43.6% of the sample (n = 654) and more frequently to women; 78.4% of prescriptions were for BZD/Z drugs with a short half-life. The majority of patients (83.5%) were prescribed only one type of BZD/Z, but 16.5% had been prescribed multiple BZD/Z drugs, with no gender difference. Doses higher than those recommended for older adults were prescribed to 58% of patients, being the doses significantly higher for men compared to women (70.0% vs 53.1%). Conclusions Over 40% of older adults presenting for emergency care after a fall had previously been prescribed BZD/Z drugs. Some important gender differences in the prescription of BZD/Z drugs were seen, especially prescription above the recommended dose and of drugs with a long-half life.
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Objective: We assessed the effects of programmed exercise (PE) on sleep quality and insomnia in middle-aged women (MAW). Methods: Searches were conducted in five databases from inception through December 15, 2016 for randomized controlled trials (RCTs) evaluating the effects of PE versus a non-exercising control condition on sleep quality, sleep disturbance and/or insomnia in MAW. Interventions had to last at least 8 weeks. Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and insomnia with the Insomnia Severity Index (ISI). Random effects models were used for meta-analyses. The effects on outcomes were expressed as mean differences (MDs) and their 95% confidence intervals (CI). Results: Five publications reported data from four RCTs on PE effects during 12-16 weeks on sleep quality (n=4 studies reporting PSQI results) and/or insomnia (n=3 studies reporting ISI results), including 660 MAW. Low-moderate levels of exercise significantly lowered the PSQI score (MD=-1.34; 95% CI -2.67, 0.00; p=0.05) compared with controls. In a subgroup analysis, moderate PE (aerobic exercise) had a positive effect on sleep quality (PSQI score MD=-1.85; 95% CI -3.62, -0.07; p=0.04), while low levels of physical activity (yoga) did not have a significant effect (MD-0.46, 95% CI -1.79, 0.88, p=0.50). In three studies (two studies of yoga, one study of aerobic exercise), there was a non-significant reduction in the severity of insomnia measured with the ISI score (MD -1.44, 95% CI -3.28, 0. 44, p=0.13) compared with controls. Heterogeneity of effects among studies was moderate to high. Conclusion: In middle-aged women, programmed exercise improved sleep quality but had no significant effect on the severity of insomnia.
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Importance Effective, practical, nonpharmacologic therapies are needed to treat menopause-related insomnia symptoms in primary and women’s specialty care settings. Objective To evaluate the efficacy of telephone-based cognitive behavioral therapy for insomnia (CBT-I) vs menopause education control (MEC). Design, Setting, and Participants A single-site, randomized clinical trial was conducted from September 1, 2013, to August 31, 2015, in western Washington State among 106 perimenopausal or postmenopausal women aged 40 to 65 years with moderate insomnia symptoms (Insomnia Severity Index [ISI] score, ≥12) and 2 or more daily hot flashes. Blinded assessments were conducted at baseline, 8, and 24 weeks postrandomization. An intent-to-treat analysis was conducted. Interventions Six CBT-I or MEC telephone sessions in 8 weeks. Participants submitted weekly electronic sleep diaries and received group-specific written educational materials. The CBT-I sessions included sleep restriction, stimulus control, sleep hygiene education, cognitive restructuring, and behavioral homework; MEC sessions provided information about menopause and women’s health. Main Outcomes and Measures Primary outcome was scores on the ISI (score range, 0-28; scores ≥15 indicate moderate to severe insomnia). Secondary outcome was scores on the Pittsburgh Sleep Quality Index (score range, 0-21; higher scores indicate worse sleep quality). Additional outcomes included sleep and hot flash diary variables and hot flash interference. Results At 8 weeks, ISI scores had decreased 9.9 points among 53 women receiving CBT-I (mean [SD] age, 55.0 [3.5] years) and 4.7 points among 53 women receiving MEC (age, 54.7 [4.7] years), a mean between-group difference of 5.2 points (95% CI, –6.1 to –3.3; P < .001). Pittsburgh Sleep Quality Index scores decreased 4.0 points in women receiving CBT-I and 1.4 points in women receiving MEC, a mean between-group difference of 2.7 points (95% CI, –3.9 to –1.5; P < .001). Significant group differences were sustained at 24 weeks. At 8 and 24 weeks, 33 of 47 women (70%) and 37 of 44 (84%) in the CBT-I group, respectively, had ISI scores in the no-insomnia range compared with 10 of 41 (24%) and 16 of 37 (43%) in the MEC group, respectively. The CBT-I group also had greater improvements in diary-reported sleep latency, wake time, and sleep efficiency. There were no between-group differences in frequency of daily hot flashes, but hot flash interference was significantly decreased at 8 weeks for the CBT-I group (–15.7; 95% CI, –20.4 to –11.0) compared with the MEC group (–7.1; 95% CI, –14.6 to 0.4) (P = .03), differences that were maintained at 24 weeks for the CBT-I group (–22.8; 95% CI, –28.6 to –16.9) and MEC group (–11.6; 95% CI, –19.4 to –3.8) (P = .003). Conclusions and Relevance Telephone-based CBT-I improved sleep in perimenopausal and postmenopausal women with insomnia and hot flashes. Results support further development and testing of centralized CBT-I programs for treating menopausal insomnia. Trial Registration clinicaltrials.gov Identifier: NCT01936441
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