Effects of cognitive behavioural therapy and bright light therapy for insomnia in youths with eveningness: study protocol for a randomised controlled trial.

BACKGROUND: Insomnia and eveningness are common and often comorbid conditions in youths. While cognitive behavioural therapy for insomnia (CBT-I) has been suggested as a promising intervention, it remains unclear whether it is sufficient to also address circadian issues in youths. In addition, despite that light has been shown to be effective in phase-shifting one's circadian rhythm, there has been limited data on the effects of bright light therapy and its combination with CBT-I on sleep and circadian outcomes in youths. The current protocol outlines a randomised controlled trial that examines the efficacy of CBT-I and CBT-I plus bright light therapy (BLT) in reducing insomnia severity, improving mood symptoms and daytime functioning (e.g. sleepiness, fatigue, cognitive function), and improving subjective and objective sleep and circadian measures compared to a waitlist control group. METHODS: We will carry out a randomised controlled trial (RCT) with 150 youths aged 12-24 who meet the criteria of insomnia and eveningness. Participants will be randomised into one of three groups: CBT-I with bright light therapy, CBT-I with placebo light, and waitlist control. Six sessions of CBT-I will be delivered in a group format, while participants will be currently asked to use a portable light device for 30 min daily immediately after awakening throughout the intervention period for bright light therapy. The CBT-I with light therapy group will receive bright constant green light (506 lx) while the CBT-I with placebo light group will receive the modified light device with the LEDs emitting less than 10 lx. All participants will be assessed at baseline and post-treatment, while the two active treatment groups will be additionally followed up at 1 month and 6 months post-intervention. The primary outcome will be insomnia severity, as measured by the Insomnia Severity Index. Secondary outcomes include self-reported mood, circadian, daytime functioning, and quality of life measures, as well as sleep parameters derived from actigraphy and sleep diary and neurocognitive assessments. Objective measures of the circadian phase using dim-light melatonin onset assessment and sleep parameters using polysomnography will also be included as the secondary outcomes. DISCUSSION: This study will be the first RCT to directly compare the effects of CBT-I and BLT in youths with insomnia and eveningness. Findings from the study will provide evidence to inform the clinical management of insomnia problems and eveningness in youths. TRIAL REGISTRATION: ClinicalTrials.gov NCT04256915. Registered on 5 February 2020.

Objective and subjective sleep in patients with non-seasonal major depressive disorder and eveningness - Results from a randomized controlled trial of bright light therapy.

STUDY OBJECTIVES: This study examines the (dis)agreement between objective and subjective sleep and their prospective changes in a randomized controlled trial of bright light therapy (BLT) in patients with major depressive disorder (MDD) and eveningness. METHODS: A total of 93 adults were randomized to receive either 30-min daily of 10,000 lux BLT or 50lux placebo dim red light therapy (DRL group) for a total of 5 weeks. Actigraphic data were collected at the baseline and during the last week of treatment. (Dis)Concordance of diary and actigraphic sleep parameters were assessed by partial correlations and Bland-Altman plots, and the associations between these discrepancies to depression severity was assessed by linear regression models. Changes of sleep parameters were assessed by linear mixed models. RESULTS: Significant correlations were found between subjective sleep timings and chronotype to actigraphic parameters. Discrepancies between diary- and actigraphic-measures were observed, and patients with more severe depressive symptoms were associated with a greater under-estimation of total sleep time (TST). A greater advance in the diary-based time to fall sleep and rise time were achieved in the BLT group as compared to the DRL group, while diary-based wake after sleep onset (WASO), TST and sleep efficiency (SE) comparably improved with time in both groups. There was no significant difference between the two groups in the actigraphic parameters after treatment. CONCLUSIONS: In this study, we found that depression severity influenced subjective report of sleep. BLT led to a greater advance in subjective sleep timings when compared to the placebo group.

Prediction of Dropout in a Randomized Controlled Trial of Adjunctive Light Treatment in Patients with Non-Seasonal Depression and Evening Chronotype.

The current study examined the possible predictors of dropout during a five-week light treatment (LT) with a gradual advance protocol in 93 patients with unipolar non-seasonal depression and evening chronotypes by comparing their clinical characteristics and performing a logistic regression analysis. Nineteen out of ninety-three (20%) subjects (80% female, 46.5 ± 11.7 years old) dropped out during the 5-week light treatment. Treatment non-adherence (i.e., receiving LT for less than 80% of the prescribed duration) over the first treatment week predicted a five-fold increase in risk of dropout during light therapy (OR: 5.85, CI: 1.41-24.21) after controlling for potential confounders, including age, gender, treatment group, rise time at the baseline, patient expectation, and treatment-emergent adverse events. There is a need to incorporate strategies to enhance treatment adherence and retention in both research and clinical settings. Chinese clinical trial registry (ChiCTR-IOR-15006937).

Change in circadian preference predicts sustained treatment outcomes in patients with unipolar depression and evening preference.

STUDY OBJECTIVES: Eveningness is associated with worse outcomes in depression. It remained unclear if eveningness could be altered with chronobiological therapy and whether such a change would predict long-term outcomes of depression. METHODS: Data from a randomized controlled trial of 5-week adjunctive bright light therapy with a gradual advance protocol conducted in 91 adult patients with nonseasonal unipolar depression and eveningness (Morningness-Eveningness Questionnaire, score ≤ 41) was examined. "Change of eveningness" was defined by Morningness-Eveningness Questionnaire score over 41 at posttreatment week 5 and "persistent change of eveningness" was defined as maintenance of Morningness-Eveningness Questionnaire score > 41 throughout the follow-up period from week 5 to posttreatment 5 months. RESULTS: Thirty-three participants (36%) had change of eveningness at week 5. Generalized estimating equations models showed that a change of eveningness at week 5 predicted a 2-fold increase in remission of depression over the 5-month follow up (odds ratio = 2.61 95% confidence interval 1.20-5.71, P = .016). Twenty-five participants (75.7%) had a persistent change and were more likely to achieve a remission of depression over the 5-month follow up (odds ratio = 3.18, 95% confidence interval: 1.35-7.50, P = .008). CONCLUSIONS: One-third of the patients with depression changed their evening-preference after 5-week of chronotherapeutic treatment, and such change predicted a higher likelihood of depression remission over 5 months of follow-up. CLINICAL TRIAL REGISTRATION: Registry: Chinese Clinical Trial Registry; Name: Adjunctive light treatment in major depressive disorder patients with evening chronotype-A randomized controlled trial; URL: https://www.chictr.org.cn/showprojen.aspx?proj=11672; Identifier: ChiCTR-IOR-15006937. CITATION: Chan JWY, Chan NY, Li SX, et al. Change in circadian preference predicts sustained treatment outcomes in patients with unipolar depression and evening preference. J Clin Sleep Med. 2022;18(2):523-531.

Non-pharmacological Approaches for Management of Insomnia.

Insomnia is a prevalent sleep problem associated with a constellation of negative health-related outcomes and significant socioeconomic burden. It commonly co-occurs with psychiatric and medical conditions, which may further exacerbate these comorbid conditions and hinder treatment response. There is much empirical evidence to support the clinical efficacy of non-pharmacological treatment for insomnia, especially cognitive behavioral therapy for insomnia (CBT-I), in managing insomnia in a wide range of populations. This article reviews the research on the efficacy of CBT-I for primary insomnia and insomnia comorbid with other psychiatric and medical conditions, the empirical evidence regarding different CBT-I treatment modalities, the implementation of CBT-I across different age groups, and some initial evidence on the sequential combination of insomnia treatments. A brief overview of other non-pharmacological treatment with regard to complementary alternative medicine is also provided.

Disruption of sleep, sleep-wake activity rhythm, and nocturnal melatonin production in breast cancer patients undergoing adjuvant chemotherapy: prospective cohort study.

OBJECTIVE: This prospective cohort study captured the patterns of sleep, sleep-wake activity rhythm, and first-morning urinary melatonin in breast cancer patients undergoing adjuvant chemotherapy. METHODS: Breast cancer patients undergoing adjuvant chemotherapy wore wrist actigraph for 168 h and collected first-morning void urine samples before treatment, during the first, and at the last cycle of chemotherapy. We converted actigraphy data into sleep duration, sleep efficiency, nighttime total wake time, percent rhythm, F-statistic, amplitude, mesor, and acrophase. We then assessed urinary 6-sulfatoxymelatonin (aMT6s) levels. RESULTS: This cohort contained 180 participants. Compared with the baseline, sleep efficiency during the first and last cycle decreased by 10.16% [95% confidence interval (95% CI): 5.85%, 14.47%] and 5.01% (95% CI: 0.50%, 9.53%), respectively. Similarly, percent rhythm decreased by 27.20% (95% CI: 19.95%, 34.45%) during the first cycle and 21.20% (95% CI: 13.52, 28.89) during the last cycle. Taking the baseline as the reference, aMT6s levels during the first and last cycle decreased by 11.27% (95% CI: 0.37%, 22.16%) and 14.74% (95% CI: 2.34, 27.11), respectively. CONCLUSION: The first administration of adjuvant chemotherapy is associated with sleep disturbance and sleep-wake activity rhythm disruption among breast cancer patients, while the disturbance and disruption during the last cycle are less severe; nevertheless, repeated administration of chemotherapy results in progressive impairment of nocturnal melatonin production.

Depressive Symptoms, Co-Morbidities, and Glycemic Control in Hong Kong Chinese Elderly Patients With Type 2 Diabetes Mellitus.

BACKGROUND AND OBJECTIVES: Undiagnosed depression is an important comorbidity in type 2 diabetes (T2D) which can be detected using the Geriatric Depression Scale (GDS-15) questionnaire. In this cross-sectional study, we examined the associations of depression using GDS score with control of cardiometabolic risk factors and health status in elderly patients with T2D. SETTING AND PARTICIPANTS: Between February and December 2013, patients aged ≥65 years who underwent structured comprehensive assessment as a quality improvement program at the Diabetes Center of a teaching hospital were invited to complete the GDS-15 questionnaire. MAIN OUTCOME MEASURES: Depression was defined as a GDS score ≥7. Demographic data, prior history of co-morbidities, frequency of self-reported hypoglycemia, and attainment of treatment targets defined as HbA1c, <7%, blood pressure <130/80 mmHg, and LDL-C <2.6 mmol/L were documented. RESULTS: Among 325 participants (65% male, median [interquartile range] age: 69 [8] years), 42 (13%) had depression. Patients with depression had longer disease durations (mean ± SD: 15.1 ± 9.1 vs. 11.6 ± 8.1 years, P = 0.02), more frequent self-reported hypoglycemic events (17 vs. 6%, P = 0.03) and were less likely to attain all three treatment targets (0 vs. 16%, P = 0.004) than those without depression. On multivariable analysis, patients with depression had an odds ratio of 2.84 (95% confidence intervals: 1.35-6.00, P = 0.006) of reporting prior history of co-morbidities. CONCLUSION: In elderly patients with T2D, depression was not uncommon especially in those with poor control of risk factors, hypoglycemia, and co-morbidities. Inclusion of GDS-15 questionnaire during structured assessment for complications and risk factors can identify these high-risk patients for more holistic management of their physical and mental health.

Potential Mechanisms of Mindfulness in Improving Sleep and Distress.

The mechanisms of mindfulness-improved sleep quality are not extensively studied. Recently, attention monitoring/awareness and acceptance in mindfulness have been proposed to be the underlying mechanisms that tackle distress and related disorders. The current study tested if acceptance moderated the relationship of awareness with psychological distress and sleep quality, and verified that psychological distress mediated the relationship between mindfulness and sleep quality in a group of community-dwelling healthy adults. Three hundred and sixty-four healthy Chinese non-meditators (age 18-65, 59% female) completed a set of online self-reported questionnaires in Chinese via SurveyMonkey. Awareness and acceptance were measured by Observe and Nonreact facets in the Five Facet Mindfulness Questionnaire (FFMQ), respectively. General psychological distress levels and sleep quality were reflected in the global score of the Depression Anxiety and Stress Scales (DASS) and the Pittsburgh Sleep Quality Index (PSQI), respectively. Model 1 and model 8 in the PROCESS macro for SPSS were used to assess the moderation and moderated mediation effects. Increased level of acceptance (Nonreact) weakened the positive relationship between awareness (Observe) and poor sleep quality (ß = -0.0154, p = 0.0123), which was partially mediated through perceived psychological distress (ß = -0.0065, 95% bias-corrected bootstrap CI = -0.0128, -0.0004) in a group of community-dwelling healthy adults. Our findings suggested that awareness and acceptance could be the mechanisms of mindfulness interventions in improving sleep quality, partly via reducing psychological stress.

Comparing the Effects of Mindfulness-Based Cognitive Therapy and Sleep Psycho-Education with Exercise on Chronic Insomnia: A Randomised Controlled Trial.

BACKGROUND: Mindfulness-based cognitive therapy (MBCT) is a potential treatment for chronic insomnia. We evaluated the efficacy of MBCT for insomnia (MBCT-I) by comparing it with a sleep psycho-education with exercise control (PEEC) group. METHODS: Adults with chronic primary insomnia (n = 216) were randomly allocated to the MBCT-I or PEEC group. The MBCT-I included mindfulness and psycho-education with cognitive and behavioural components under cognitive behavioural therapy for insomnia. PEEC included psycho-education of sleep hygiene and stimulus control, and exercises. Any change in insomnia severity was measured by the Insomnia Severity Index (ISI). Secondary outcomes included sleep parameters measured by a sleep diary, health service utilisation, absence from work and mindfulness measured by the Five Facet Mindfulness Questionnaire. RESULTS: The ISI score significantly decreased in the MBCT-I group compared with the PEEC group at 2 months (i.e., post-intervention) (p = 0.023, effect size [95% CI] -0.360 [-0.675, -0.046]) but not at 5 or 8 months. Treatment response rates and remission rates based on the ISI cut-off scores were not significantly different between groups. Wake time after sleep onset (WASO) was less in the MBCT-I group at 2 and 5 months. At 8 months, both groups showed a reduced ISI score, sleep onset latency and WASO, and increased sleep efficiency and total sleep time; however, no group differences were seen. Other outcome measures did not significantly improve in either group. CONCLUSIONS: Long-term benefits were not seen in MBCT-I when compared with PEEC, although short-term benefits were seen.

Help-seeking behaviors for insomnia in Hong Kong Chinese: a community-based study.

OBJECTIVES: To determine the prevalence and correlates of help-seeking behaviors for insomnia in Hong Kong Chinese middle-aged adults and their offspring. METHODS: A total of 2231 middle-aged adults (54.2% females, mean age 45.8 years) and 2186 children and adolescents (51.9% females, mean age 13.4 years) completed a questionnaire on insomnia symptoms, daytime functioning, health condition and treatments sought for insomnia. RESULTS: A total of 40% of adults and 10% of children and adolescents with insomnia reported having sought treatment for insomnia. Conventional Western medicine was the commonly preferred treatment in 33.3% of adults and 13.3% of children and adolescents who sought help for insomnia, while a higher proportion of individuals with insomnia (34.5% of adults and 26.7% of children and adolescents) sought help from complementary and alternative medicine (CAM) therapies. Female gender (odds ratio [OR] [95% confidence interval, CI] = 2.14 [1.01-4.53]), higher family income (≥15,000 HKD/month) (OR [95% CI] = 3.15 [1.27-6.34]), severity of insomnia (Insomnia Severity Index ≥14) (OR [95% CI] = 2.12 [1.10-4.12]), chronic medications (OR [95% CI] = 4.71 [2.27-9.79]), and psychiatric disorders (OR [95% CI] = 2.83 [1.01-7.96]) were associated with help-seeking behaviors in adults. Presence of morning headache was associated with help-seeking behaviors in children and adolescents (OR [95% CI] = 8.66 [1.72-43.70]). CONCLUSIONS: It is uncommon for Hong Kong Chinese to seek help for insomnia, despite the high prevalence of insomnia. The significant unmet need argues for timely intervention to promote sleep-health literacy and to enhance the awareness and accessibility of evidence-based treatment for insomnia.

Hypnotic effects of a novel anti-insomnia formula on Drosophila insomnia model.

OBJECTIVE: To assess the biological effects of the six-herb mixture Anti-Insomia Formula (AIF) extract using caffeine-induced insomnia Drosophila model and short-sleep mutants. METHODS: Caffeineinduced insomnia wild-type Drosophila and short-sleep mutant flies minisleep (mns) and Hyperkinetic(Y) (Hk(Y)) were used to assess the hypnotic effects of the AIF in vivo. The night time activity, the amount of night time sleep and the number of sleep bouts were determined using Drosophila activity monitoring system. Sleep was defined as any period of uninterrupted behavioral immobility (0 count per minute) lasting > 5 min. Night time sleep was calculated by summing up the sleep time in the dark period. Number of sleep bouts was calculated by counting the number of sleep episodes in the dark period. RESULTS: AIF at the dosage of 50 mg/mL, effectively attenuated caffeine-induced wakefulness (P<0.01) in wild-type Canton-S flies as indicated by the reduction of the sleep bouts, night time activities and increase of the amount of night time sleep. AIF also significantly reduced sleeping time of short-sleep Hk(Y) mutant flies (P<0.01). However, AIF did not produce similar effect in mns mutants. CONCLUSION: AIF might be able to rescue the abnormal condition caused by mutated modulatory subunit of the tetrameric potassium channel, but not rescuing the abnormal nerve firing caused by Shaker gene mutation. This study provides the scientific evidence to support the use of AIF in Chinese medicine for promoting sleep quality in insomnia.

The effectiveness of acupuncture on the sleep quality of elderly with dementia: a within-subjects trial.

PURPOSE: Elderly with dementia are often afflicted with sleep problems. Recent studies have suggested that acupuncture may be a feasible alternative to traditional sleep medicine for treating sleep disturbance. This study investigated the effectiveness of acupuncture on sleep quality of elderly with dementia. PATIENTS AND METHODS: Nineteen elders with dementia were followed through a control period and an acupuncture treatment period, each lasting 6 weeks. Outcome measures were subjects' sleep quality and cognitive function. Sleep parameters were recorded by wrist actigraphy. Cognitive function was assessed by the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog). Pretests and posttests were conducted immediately before and after the control and treatment periods. Changes in the outcome measures between control and treatment periods were compared. RESULTS: Wilcoxon signed rank tests revealed that the subjects gained significantly more resting time and total sleep time in the treatment period than in the control period (P < 0.05). A nonsignificant trend for improvement in sleep efficiency was observed. Improvement in cognitive function was not statistically significant. A total of 86% of the subjects completed the treatment regime. CONCLUSION: Results reveal that acupuncture was effective in improving some domains of sleep quality of elderly with dementia, and the subjects showed acceptance towards the intervention. Strengths and limitations of the present study as well as suggestions for further studies were considered.

Frequent nightmares in children: familial aggregation and associations with parent-reported behavioral and mood problems.

STUDY OBJECTIVES: To conduct a systematic investigation on the prevalence, correlates, and familial aggregation of frequent nightmares in children, and to scrutinize the associations between frequent nightmares and parent-reported behavioral and mood problems in children. DESIGN: A cross-sectional study was conducted by collecting the data on sociodemographic, sleep, behavioral, and family-related information from a total of 6359 children (age: mean [SD]=9.2 [1.8] years; girls: 49.9%) and their reported biological parents. SETTING: Community. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Prevalence of frequent nightmares with a criterion of at least once per week was 5.2%. Multinomial regression analysis indicated that monthly family income, paternal and maternal nightmares, insomnia symptoms, parasomniac symptoms, and daytime consequences were significantly associated with nightmares in children. Frequent nightmares in children were significantly associated with hyper-activity (odds ratio [OR]=1.68, 95% CI 1.16-2.44), frequent temper outbursts/mood disturbance (OR=1.76, 95%CI 1.27-2.44), and poor academic performance (OR=1.62, 95% CI 1.11-2.36), after controlling for potential confounding factors. Approximately 20% of children with frequent nightmares experienced comorbid frequent insomnia. Comorbid nightmares and insomnia were associated with increased odds of hyperactivity (OR=4.13, 95% CI 2.13-8.00) and frequent temper outbursts/mood disturbance (OR=2.41, 95%CI 1.27-4.60). CONCLUSIONS: Frequent nightmares in children are associated with a constellation of child-, sleep-, and family-related factors, including comorbid sleep problems, such as insomnia and parasomnia, family economic status, and parental predisposition. Frequent nightmares are independently associated with emotional and behavioral problems in children.