The assessment and management of insomnia: an update

Insomnia poses significant challenges to public health. It is a common condition associated with marked impairment in function and quality of life, psychiatric and physical morbidity, and accidents. As such, it is important that effective treatment is provided in clinical practice. To this end, this paper reviews critical aspects of the assessment of insomnia and the available treatment options. These options include both non‐medication treatments, most notably cognitive behavioral therapy for insomnia, and a variety of pharmacologic therapies such as benzodiazepines, “z‐drugs”, melatonin receptor agonists, selective histamine H1 antagonists, orexin antagonists, antidepressants, antipsychotics, anticonvulsants, and non‐selective antihistamines. A review of the available research indicates that rigorous double‐blind, randomized, controlled trials are lacking for some of the most commonly administered insomnia therapies. However, there are an array of interventions which have been demonstrated to have therapeutic effects in insomnia in trials with the above features, and whose risk/benefit profiles have been well characterized. These interventions can form the basis for systematic, evidence‐based treatment of insomnia in clinical practice. We review this evidence base and highlight areas where more studies are needed, with the aim of providing a resource for improving the clinical management of the many patients with insomnia.     

Consumers using the Internet for insomnia information: The who,what, and why

Information obtained from the Internet often influences the treatment choices of patients with insomnia. This study explored patterns of online information seeking and utilization among patients with insomnia. A total of 1013 participants took part in an online survey about sleep health information between July 2012 and March 2013. Participants also completed the Insomnia Severity Index and the Dysfunctional Beliefs and Attitudes about Sleep Scale. The results showed that those seeking insomnia-related information resources frequently searched online, and the information found appeared to influence important health behaviors such as treatment decisions, taking medication and whether to seek professional care. Information of interest revolved around insomnia treatment options and symptomology. While no predictors for Internet use were identified, the Internet does represent an important health-care portal for insomnia patients and warrants further investigation as targeted e-health interventions become more prominent in the routine management of insomnia.

     

Meta-analysis of benzodiazepine use in the treatment of insomnia

OBJECTIVE: To systematically review the benefits and risks associated with the use of benzodiazepines to treat insomnia in adults. DATA SOURCES: MEDLINE and the Cochrane Controlled Trials Registry were searched for English-language articles published from 1966 to December 1998 that described randomized controlled trials of benzodiazepines for the treatment of insomnia. Key words included "benzodiazepines" (exploded), "randomized controlled trial" and "insomnia." Bibliographies of relevant articles were reviewed for additional studies and manufacturers of benzodiazepines were asked to submit additional randomized controlled trial reports not in the literature. STUDY SELECTION: Articles were considered for the meta-analysis if they were randomized controlled trials involving patients with insomnia and compared a benzodiazepine with placebo or another active agent. Of the 89 trials originally identified, 45 met our criteria, representing a total of 2672 patients. DATA EXTRACTION: Data were extracted regarding the participants, the setting, details of the intervention, the outcomes (including adverse effects) and the methodologic quality of the studies. DATA SYNTHESIS: The meta-analyses of sleep records indicated that, when compared with placebo, benzodiazepines decreased sleep latency by 4.2 minutes (non-significant; 95% confidence interval (CI -0.7 to 9.2) and significantly increased total sleep duration by 61.8 minutes (95% CI 37.4 to 86.2). Patient-reported outcomes were more optimistic for sleep latency; those randomized to benzodiazepine treatment estimated a sleep latency decrease of 14.3 minutes (95% CI 10.6 to 18.0). Although more patients receiving benzodiazepine treatment reported adverse effects, especially daytime drowsiness and dizziness or light-headedness (common odds ratio 1.8, 95% CI 1.4 to 2.4), dropout rates for the benzodiazepine and placebo groups were similar. Cognitive function decline including memory impairment was reported in several of the studies. Zopiclone was not found to be superior to benzodiazepines on any of the outcome measures examined. INTERPRETATION: The use of benzodiazepines in the treatment of insomnia is associated with an increase in sleep duration, but this is countered by a number of adverse effects. Additional studies evaluating the efficacy of nonpharmacological interventions would be valuable.     

Treatment-resistant residual insomnia in patients with recurrent major depressive episodes

Residual symptoms are common in depression, and their presence is associated with poorer clinical outcomes of depression. We conducted a case series study of first-onset major depression to elucidate the clinical course of residual insomnia and examine the relationship between residual insomnia and recurrence of depression. Subjects were 128 patients (57 males; mean age 52.8 years) with first-onset major depression. For all patients, we continuously assessed the number and breakdown of residual symptoms listed on the 17-item Hamilton Rating Scale for Depression and quantities of prescribed psychotropic medications during the depressive and remission phases. Even during the first remission phase, 85.9% of the patients with first-onset major depression experienced an average of 2.95 residual symptoms. The most common residual symptom was insomnia (65.4%), followed by reduced work and interests (43.3%) and fatigue (39.4%). Each additional recurrence resulted in a significantly shorter remission phase as well as significant increases in antidepressant and hypnotics dosages. Hypnotics dosage during the first remission phase for patients with three or more recurrent episodes was significantly higher than that for those with only a single episode. Our findings suggest a possible link between treatment-resistant residual insomnia during the first remission phase and recurrence risk of depression. In particular, it is possible that presence of treatment-resistant insomnia during the first remission phase is related to later recurrence of depressive episodes. It is important to see patients with treatment-resistant insomnia of early stage carefully, with special attention to treatment adherence.

     

Efficacy of cognitive behavioral therapy for comorbid insomnia: a meta-analysis

Sleep and Biological Rhythms - Although cognitive behavioral therapy (CBT-I) has been recommended for the treatment of insomnia comorbid with psychiatric disorders and medical diseases, the...     

The heritability of insomnia: A meta-analysis of twin studies

Twin studies of insomnia exhibit heterogeneity in estimates of heritability. This heterogeneity is likely because of sex differences, age of the sample, the reporter and the definition of insomnia. The aim of the present study was to systematically search the literature for twin studies investigating insomnia disorder and insomnia symptoms and to meta-analyse the estimates of heritability derived from these studies to generate an overall estimate of heritability. We further examined whether heritability was moderated by sex, age, reporter and insomnia symptom. A systematic literature search of five online databases was completed on 24 January 2020. Two authors independently screened 5644 abstracts, and 160 complete papers for the inclusion criteria of twin studies from the general population reporting heritability statistics on insomnia or insomnia symptoms, written in English, reporting data from independent studies. We ultimately included 12 papers in the meta-analysis. The meta-analysis focussed on twin intra-class correlations for monozygotic and dizygotic twins. Based on these intra-class correlations, the meta-analytic estimate of heritability was estimated at 40%. Moderator analyses showed stronger heritability in females than males; and for parent-reported insomnia symptoms compared with self-reported insomnia symptoms. There were no other significant moderator effects, although this is likely because of the small number of studies that were comparable across levels of the moderators. Our meta-analysis provides a robust estimate of the heritability of insomnia, which can inform future research aiming to uncover molecular genetic factors involved in insomnia vulnerability.     

The impact of insomnia and sleep disturbances on depression and suicidality.

Previous research has demonstrated an association between suicidality and sleep, suggesting that sleep disturbances may exacerbate mood dysregulation in participants suffering from mood disorders. The purpose of this study was to investigate the impact of sleep disturbances and insomnia on depression and suicidality in a nontreatment seeking sample of college students. Results indicated that insomnia and nightmares were significant predictors of symptoms of depression, while only nightmares significantly predicted suicidal ideation. Further analysis indicated that participants with elevated scores on insomnia, nightmares, or both experienced differing levels of depression and suicidal ideation. Future directions and treatment implications are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Patient-reported benefits from the pre-sleep routine approach to treating insomnia: Findings from a treatment development trial

Sleep and Biological Rhythms - This uncontrolled trial evaluated the feasibility, acceptability, and initial changes in sleep associated with a novel cognitive-behavioral treatment for insomnia,...     

Determinants of insomnia in relatively healthy elderly. A literature review

A review is presented based on the findings resulting from interview and questionnaire research concerning factors that determine insomnia in relatively healthy elderly. The investigated factors include modes of living, sleep wishes and personality aspects. During the period 1988-1997 18 published reports were found. Based on the findings it is difficult to claim that elderly persons with insomnia are characterized by inappropriate modes of living. There were, however, some (inconsistent) indications that tea consumption, smoking and lack of exercise predicted insomnia. There were also scarce indications for less realistic sleep expectations in bad than in good sleepers. More bad sleepers perceived their sleep as uncontrollable and unpredictable than than good sleepers. Bad sleepers had significantly higher scores for anxiety, neuroticism and depression than good sleepers. Anxiety as well as depression correlated positively with insomnia and negatively with sleep duration. Depression, anxiety or neuroticism often were better predictors of insomnia than health indicators such as perceived health and number of prescribed drugs. The findings suggest that insomnia in relatively healthy elderly is more tightly associated with psychological factors than with modes of living or health indicators. This has some consequences for therapy. In addition to advice concerning modes of living and sleep hygiene, one has to be alert for the possible presence of depression or anxiety. In that case depression or anxiety has to be treated, pharmacologically or nonpharmacologically.     

Subjective sleep characteristics in primary insomnia versus insomnia with comorbid anxiety or mood disorder

Sleep and Biological Rhythms - We assessed subjective sleep measures in a cohort of 146 patients with chronic insomnia and hypothesized that these measures may differ depending on the presence as...     

Variations in circadian genes and individual nocturnal symptoms of insomnia. The HUNT study

Insomnia is a condition characterized by three nocturnal symptoms: problems with sleep onset or maintenance and early morning awakenings (terminal insomnia). Affected individuals may present one or more of these symptoms. Several studies have shown that insomnia is moderately heritable and that proxy phenotypes for the three insomnia symptoms show different heritabilities. This suggests that different nocturnal symptoms of insomnia may arise from different genetic and biological backgrounds. Circadian genes are good candidates to account for these differences as they regulate the periodicity of several physiological functions including sleep. Evidence from studies in animals and humans have suggested that circadian genes might be involved in sleep disturbances such as insomnia. In this study, we investigated the association between Single Nucleotide Polymorphisms (SNPs) in circadian genes and individual symptoms of insomnia and their combinations using data from the Nord-Trøndelag Health Study 3 (the HUNT3 study, N = 50807). Participants (N = 6029) provided information about sleep onset insomnia, maintenance insomnia, and terminal insomnia. Participants who responded “several times a week” to at least one question regarding the mentioned symptoms were classified as cases (N = 3577) and categorized in seven subgroups according to possible symptom combinations. Controls (N = 2452) answered “Never/Seldom” to all sleep-related questions. Using multinomial regression, we assessed 73 SNPs in nine circadian genes (PER1, 2, 3, CRY1, 2, TIMELESS, CLOCK, REV-ERBα, ARNTL) for differences among symptoms subgroups. Twenty-five SNPs showed significant p-values and supportive odds-ratios. All significant SNPs in PER3 were associated with reporting all three symptoms simultaneously. SNPs in CRY genes were associated with terminal insomnia alone or in combination with other symptoms. Genes PER1 and two were mostly associated with sleep maintenance insomnia. However, none of the SNPs remained significant after False Discovery Rate (FDR) correction for multiple statistical testing. In conclusion, even though none of the SNPs remained significant after FDR correction, the clustering of some genes around specific symptoms points to the need for additional research on these relationships.     

Effects of two-session group cognitive behavioral therapy for psychophysiological insomnia: A preliminary study

Sleep and Biological Rhythms - The authors evaluated the effects of brief group cognitive behavioral therapy for insomnia (G-CBT-I) in outpatients with psychophysiological insomnia (PPI). This...     

医学研究生失眠现状及其相关因素的调查研究

目的 了解医学研究生失眠现状及其相关因素,为提高医学研究生生活质量和促进高层次人才的培养提供建议.方法 采用一般资料调查表、阿森斯失眠量表及中文版压力知觉量表于2020年4月17日～5月2日通过网络平台对某医科大学在读硕士研究生进行问卷调查,并进行统计分析.结果 本研究共收集416份有效问卷,有45.9％的在读医学研究...     

Effect of ramelteon coadministered with antidepressant in patients with insomnia and major depressive disorder: an exploratory study

Sleep and Biological Rhythms - The purpose is to evaluate the effect and safety of ramelteon 8 mg/day for 8 weeks in the treatment of insomnia in patients with concurrent...     

Clinical significance and management of insomnia

Sleep and Biological Rhythms - Several epidemiological studies have shown that more than 20% of the general adult population has symptoms of insomnia, but only about 5% of them are receiving...     

Unbalanced resting-state networks activity in psychophysiological insomnia

Sleep and Biological Rhythms - Psychophysiological insomnia (PI) is a clinical condition characterized by sleep-related disturbing cognitive activity and biased self-related information processing....     

Trajectories of sleepiness and insomnia symptoms in Norwegian nurses with and without night work and rotational work

Numerous cross-sectional studies report high prevalence rates of sleepiness and insomnia in shift workers, but few longitudinal studies exist. We investigated trajectories of sleepiness and insomnia symptoms in a sample of Norwegian nurses across four measurements, spanning a total of four years (sleepiness) and five years (insomnia). The participants completed the Epworth Sleepiness Scale and the Bergen Insomnia Scale at each measurement instance. Latent growth curve models were used to analyse the data. Separate models examined night work (night work, entering and leaving night work) and rotational work (rotational work, entering and leaving rotational work) as predictors for trajectories of sleepiness and insomnia symptoms, respectively. Baseline values of sleepiness and insomnia were higher among rotational shift workers than among workers with fixed shifts (day or night). The results showed that night work throughout the period and entering night work during the period were not associated with different trajectories of sleepiness or insomnia symptoms, compared to not having night work. The same results were found for rotational work and entering rotational work, compared to not having rotational work. Leaving night work and leaving rotational work were associated with a decrease in sleepiness and insomnia symptoms, compared to staying in such work.     

Serum melatonin levels and insomnia in patients with Machado-Joseph Disease

We previously reported a patient with Machado-Joseph Disease (MJD) who had severe insomnia and a low serum melatonin (MLT) level, and whose insomnia was alleviated by oral MLT replacement therapy. The aims of this study were to examine whether patients with MJD are likely to have insomnia, and whether there is a relationship between the degree of insomnia and the serum MLT level among patients with MJD. This study included 8 patients with MJD. A 58-year-old-patient with cervical spondylosis was also included in this study to check the condition of the test room for sleeping. All patients filled out the Japanese version of Pittsburgh Sleep Quality Index (PSQI-J) questionnaire. We obtained blood samples at 12:00 and 24:00 hours to measure the MLT level. We checked the sleep condition of the patient once an hour and recorded the grade in sleep-logs: the grades of sleep condition were asleep, sleepy, or awake. Statistical analyses were performed to search for correlations between the PSQI score and the serum MLT level or actual sleep time using Spearman’s rank correlation coefficient. Seven of the 8 MJD patients had a total PSQI score of above 5.5 (cut-off level). The daytime MLT level (at 12:00 hours) was below 2.8 pg/mL in all 8 patients, whereas the mean night-time MLT level (at 24:00 hours) of the MJD patients (23.6 ± 17.5 pg/mL) was lower than that of the control patient (43.0 pg/mL) and also lower than the reported cut-off level among healthy people aged 30–50 years (55.5 pg/mL). There was a negative correlation between the total PSQI score and the serum MLT level among the MJD patients (P < 0.05). Our results show that a low serum MLT level may contribute to insomnia in patients with MJD.

     

基于网络药理学、分子对接和实验验证探讨朱茯苓用于失眠的作用机制

为探讨朱茯苓治疗失眠的可能作用机制,通过TCMSP、BAT-MAN、TCMID和STITCH数据库以及文献挖掘筛选朱茯苓的活性成分及潜在靶点,利用TTD、OMIM、GeneCards和CTD数据库获取失眠类疾病的相关靶点,采用Cyto-scape软件和String数据库构建活性成分-靶点网络和靶点蛋白相互作用网络,通过...