Is Metabolic Rate Increased in Insomnia Disorder? A Systematic Review

Background: Insomnia disorder is a highly prevalent health condition, affecting ~10–15% of the adult population worldwide. A central feature of insomnia is hyperarousal characterized as persistent and increased somatic, cognitive and cortical stimulation. Hyperarousal leads to a state of conditioned arousal that disrupts both sleep and daytime function. Research studies have shown increases in body temperature, heart rate, electroencephalographic activity, catecholamines, and oxygen consumption as a measure of metabolic rate. These findings provide evidence of increased physiological activation in insomnia however results are not consistent. The aim of the systematic review was to determine if metabolic rate in patients with insomnia is increased in keeping with the hyperarousal hypothesis.Methods: We searched Pubmed, Web of Science, CINAHL, PsycINFO, EMBASE, and Scopus databases for observational and interventional studies that have measured metabolic rate in insomnia. Study characteristics were extracted and summarized and a risk of bias was performed for each of the studies.Results: Two reviewers screened 963 abstracts with 35 articles of interest for full-text review. Four articles evaluating 75 participants were included in this systematic review. Two studies showed increased oxygen consumption across 24 h in insomnia patients compared with good-sleeping controls. One study which measured oxygen consumption at only a single timepoint showed no difference between insomnia patients and good-sleeping controls. A further study evaluating the effect of lorazepam on oxygen consumption in patients with chronic insomnia showed that lorazepam reduced metabolic rate during the night time only.Conclusions: These findings show that metabolic rate appears to be increased across 24 h in line with the hyperarousal model of insomnia. However, these increases in metabolic rate in insomnia were minor compared to good-sleeping controls and the clinical significance is unclear. Larger, methodologically robust studies are required to confirm these findings and the effect of any increase in metabolic rate on sleep-wake disturbances or pathophysiology

Tired and lack focus? Insomnia increases distractibility

Chronic insomnia is associated with subjective daytime cognitive dysfunction, but objective corroborative data are often lacking. In this study, we use Perceptual Load Theory to objectively assess distractibility in participants with insomnia (N = 23) compared with age- and sex-matched controls (N = 23). Following overnight supervised sleep observation, all participants completed a selective attention task which varied in the level of perceptual load and distractor congruency. The insomnia group was found to be more distracted than controls, whereas their selective attention mechanism appeared to be intact, with reduced distractor processing under high load for both groups. Insomnia symptom severity was positively correlated with participant distractibility. These findings suggest that there are insomnia-related daytime cognitive impairments that are likely to arise from compromised cognitive control rather than an ineffective selective attention mechanism. This task may be clinically useful in assessing daytime impairments, and potentially treatment response, in those with insomnia

Parallel Changes in Mood and Melatonin Rhythm Following an Adjunctive Multimodal Chronobiological Intervention With Agomelatine in People With Depression: A Proof of Concept Open Label Study

Background: Agomelatine is a melatonin agonist and 5HT antagonist developed for the treatment of major depressive disorder which also has some effects on the circadian system. Since circadian dysfunctions are thought to play a role in the pathophysiology of depression, some of the mechanism of action of this drug may relate to improvements in circadian rhythms.Objective: This proof of concept open-label study sought to determine if improvements in depressive symptoms following an adjunctive multimodal intervention including agomelatine intake are associated with the magnitude of circadian realignment. This was investigated in young people with depression, a subgroup known to have high rates of delayed circadian rhythms.Methods: Young people with depression received a psychoeducation session about sleep and circadian rhythms, were asked to progressively phase advance their wake up time, and completed an 8 weeks course of agomelatine (25–50 mg). Participants underwent semi-structured psychological assessments, ambulatory sleep-wake monitoring and measurement of melatonin circadian phase before and after the intervention.Results: Twenty-four young adults with depression (17–28 years old; 58% females) completed the study. After the intervention, depressive symptoms were significantly reduced [t(23) = 6.9, p < 0.001] and, on average, the timing of dim light melatonin onset (DLMO) shifted 3.6 h earlier [t(18) = 4.4, p < 0.001]. On average, sleep onset was phase shifted 28 min earlier [t(19) = 2.1, p = 0.047] and total sleep time increased by 24 min [t(19) = –2.6, p = 0.018]. There was no significant change in wake-up times. A strong correlation (r = 0.69, p = 0.001) was found between the relative improvements in depression severity and the degree of phase shift in DLMO.Conclusion: Although this needs to be replicated in larger randomized controlled trials, these findings suggest that the degree of antidepressant response to a multimodal intervention including psychoeducation and agomelatine intake may be associated with the degree of change in evening melatonin release in young people with depression. This offers promising avenues for targeted treatment based on the prior identification of objective individual characteristics

Benzodiazepine usage and patient preference for alternative therapies: A descriptive study

Abstract Background and aims The prevalence of chronic benzodiazepine use in primary care settings remains high despite clear evidence of adverse health outcomes resulting from long‐term use and the availability of effective alternative behavioural therapies. Eliciting factors influencing past or current usage experience of benzodiazepine users and their future behavioural intention regarding discontinuation or alternative behavioural therapy adoption could be useful in developing informed strategies facilitating successful benzodiazepine withdrawal in long‐term users. The aim of this study was to identify patient factors influencing their current long‐term benzodiazepine use, past withdrawal attempt, and future intention to trial safer alternative behavioural therapies. Additionally, the study also aimed to explore patients' preference for information sources on behavioural therapies. Methods Point of purchase surveys were conducted with patients obtaining benzodiazepines from selected pharmacies across New South Wales (NSW), Australia. Survey items included the Beliefs about Medicines Questionnaire (BMQ‐specific), questions about patient's sociodemographic characteristics, as well as their views about long‐term benzodiazepine use and behavioural therapies. Results Seventy‐five patients were recruited from 12 pharmacies across New South Wales (NSW). The surveys were conducted from November 2016 to July 2017. The mean (±SD) age of the participants was 54.3 (±16.7) with a range of 23 to 86 years, and 67% of the participants had been using the benzodiazepine for at least 1 year. Lower‐education levels, stronger beliefs about the necessity of use, and lower concerns about ongoing benzodiazepine use were significantly associated with prolonged use. Sixty‐four percent of the participants were not interested in behavioural therapies, and there was a significant relationship between the participants' future preference for behavioural therapies and their concerns about the potential adverse effects of benzodiazepines. A majority of the participants rated general practitioners (GPs) as their first choice and pharmacists as the second choice for discussing behavioural therapies. Conclusions Specific individual sociodemographic characteristics of benzodiazepine users and their medication‐related beliefs influence their current benzodiazepine usage and future intention to trial behavioural therapies as an alternative to their benzodiazepines. Based on the reported preferences of benzodiazepine users in this study, developing and evaluating GP‐pharmacist collaborative services to improve the uptake of behavioural therapies as an alternative to benzodiazepines can be recommended

Summary and update on behavioral interventions for improving adherence with positive airway pressure treatment in adults

Continuous positive airway pressure (PAP) is still the most efficacious treatment for obstructive sleep apnea when used effectively. Since the availability of PAP 39 years ago there have been considerable technological advances, such as quieter, lighter and smaller machines with better humidification. However, adherence to treatment is still a major problem. This article reviews studies published on behavioral interventions aimed at improving the uptake and maintenance of PAP treatment (January 2016–February 2020). It discusses underlying factors in the poor uptake and discontinuation of treatment and the role of qualitative research to better understand the perspective of the patients

Open-label placebo for insomnia (OPIN): study protocol for a cohort multiple randomised controlled trial

Introduction Insomnia is a prevalent sleep disorder that causes substantial personal and societal harm. There is evidence that placebo interventions can reduce insomnia symptoms, but this research has involved deceptively administering the placebo under the guise of a real medication (conventional placebo, CP), which has obvious ethical constraints. Open-label placebo (OLP) treatment, in which a placebo is administered with full disclosure that there are no active ingredients, has been proposed as a method of using the placebo effect ethically, but the efficacy and acceptability of OLP for insomnia is currently unknown.Methods and analysis This study uses a cohort multiple randomised controlled trial design to compare OLP, CP and no treatment for insomnia. Two-hundred and sixty-seven participants with self-reported insomnia symptoms (Insomnia Severity Index, ISI ≥10) will be recruited into an observational study and have their sleep monitored over a 2-week period. Participants will then be randomised to one of three groups: invite to OLP, invite to CP described deceptively as a new pharmacological agent, or no invite/observational control. Those in OLP and CP accepting the invite receive identical placebos for a 2-week treatment period while sleep is monitored in all participants. The primary outcome is ISI at the end of the treatment period. Secondary outcomes include treatment uptake and clinically significant response rates, objective and subjective sleep parameters, fatigue, mood, expectancy, treatment satisfaction and side effects. Predictors of uptake and responses to OLP and CP will be explored.Ethics and dissemination The trial has been approved by The University of Sydney Human Research Ethics Committee. Written informed consent is obtained from every participant. OLP and CP participants accepting the invite undergo an additional consent process. Results will be disseminated via peer-reviewed conference proceedings and publications.Trial registration number ACTRN12620001080910

The effects of lithium carbonate supplemented with nitrazepam on sleep disturbance during cannabis abstinence

STUDY OBJECTIVES: Sleep disturbance is a hallmark feature of cannabis withdrawal. In this study we explored the effects of lithium treatment supplemented with nitrazepam on objective and subjective measures of sleep quality during inpatient cannabis withdrawal. METHODS: Treatment-seeking cannabis-dependent adults (n = 38) were admitted for 8 days to an inpatient withdrawal unit and randomized to either oral lithium (500 mg) or placebo, twice daily in a double-blind RCT. Restricted nitrazepam (10 mg) was available on demand (in response to poor sleep) on any 3 of the 7 nights. Dependent outcome measures for analysis included repeated daily objective actigraphy and subjective sleep measures throughout the 8 day detox, subjective cannabis withdrawal ratings, and detoxification completion rates. RESULTS: Based on actigraphy, lithium resulted in less fragmented sleep compared to placebo (p = 0.04), but no other objective measures were improved by lithium. Of the subjective measures, only nightmares were suppressed by lithium (p = 0.04). Lithium did not have a significant impact on the use of nitrazepam. Sleep bout length (p < 0.0001), sleep efficiency (p < 0.0001), and sleep fragmentation (p = 0.05) were improved on nights in which nitrazepam was used. In contrast, only night sweats improved with nitrazepam from the subjective measures (p = 0.04). A Cox regression with daily repeated measures of sleep efficiency averaged across all people in the study a predictor suggests that a one-unit increase in sleep efficiency (the ratio of total sleep time to the total time in bed expressed as a percentage) resulted in a 14.6% increase in retention in treatment (p = 0.008, Exp(B) = 0.854, 95% CI = 0.759–0.960). None of the other sleep measures, nor use of lithium or nitrazepam were significantly associated with retention in treatment. CONCLUSIONS: Lithium seems to have only limited efficacy on sleep disturbance in cannabis withdrawal. However the nitrazepam improved several actigraphy measures of sleep disturbance, warranting further investigation. Discord between objective and subjective sleep indices suggest caution in evaluating treatment interventions with self-report sleep data only. CITATION: Allsop DJ, Bartlett DJ, Johnston J, Helliwell D, Winstock A, McGregor IS, Lintzeris N. The effects of lithium carbonate supplemented with nitrazepam on sleep disturbance during cannabis abstinence. J Clin Sleep Med 2015;11(10):1153–1162