Simon D. Kyle

A Randomized, Placebo-Controlled Trial of Online Cognitive Behavioral Therapy for Chronic Insomnia Disorder Delivered via an Automated Media-Rich Web Application

STUDY OBJECTIVES The internet provides a pervasive milieu for healthcare delivery. The purpose of this study was to determine the effectiveness of a novel web-based cognitive behavioral therapy (CBT) course delivered by an automated virtual therapist, when compared with a credible placebo; an approach required because web products may be intrinsically engaging, and vulnerable to placebo response. DESIGN Randomized, placebo-controlled trial comprising 3 arms: CBT, imagery relief therapy (IRT: placebo), treatment as usual (TAU). SETTING Online community of participants in the UK. PARTICIPANTS One hundred sixty-four adults (120 F: [mean age 49y (18-78y)] meeting proposed DSM-5 criteria for Insomnia Disorder, randomly assigned to CBT (n = 55; 40 F), IRT placebo (n = 55; 42 F) or TAU (n = 54; 38 F). INTERVENTIONS CBT and IRT each comprised 6 online sessions delivered by an animated personal therapist, with automated web and email support. Participants also had access to a video library/back catalogue of session content and Wikipedia style articles. Online CBT users had access to a moderated social network/community of users. TAU comprised no restrictions on usual care and access to an online sleep diary. MEASUREMENTS AND RESULTS Major assessments at baseline, post-treatment, and at follow-up 8-weeks post-treatment; outcomes appraised by online sleep diaries and clinical status. On the primary endpoint of sleep efficiency (SE; total time asleep expressed as a percentage of the total time spent in bed), online CBT was associated with sustained improvement at post-treatment (+20%) relative to both TAU (+6%; d = 0.95) and IRT (+6%: d = 1.06), and at 8 weeks (+20%) relative to IRT (+7%: d = 1.00) and TAU (+9%: d = 0.69) These findings were mirrored across a range of sleep diary measures. Clinical benefits of CBT were evidenced by modest superiority over placebo on daytime outcomes (d = 0.23-0.37) and by substantial improved sleep-wake functioning on the Sleep Condition Indicator (range of d = 0.77-1.20). Three-quarters of CBT participants (76% [CBT] vs. 29% [IRT] and 18% [TAU]) completed treatment with SE > 80%, more than half (55% [CBT] vs. 17% [IRT] and 8% [TAU]) with SE > 85%, and over one-third (38% [CBT] vs. 6% [IRT] and 0% [TAU]) with SE > 90%; these improvements were largely maintained during follow-up. CONCLUSION CBT delivered using a media-rich web application with automated support and a community forum is effective in improving the sleep and associated daytime functioning of adults with insomnia disorder. CLINICAL TRIAL REGISTRATION ISRCTN - 44615689.

Insomnia and health-related quality of life.

Health-related Quality of Life (HRQoL) has become an important construct in contemporary medicine and health care, permitting assessment of disorder burden and evaluation of interventions on various aspects of functioning, in a standardized manner. Here we review literature on the measurement of HRQoL in insomnia populations, and the extent to which insomnia treatment improves domains of HRQoL. It is concluded from the relatively small literature that insomnia impacts on diverse areas of HRQoL, and that both pharmacological and non-pharmacological interventions can produce, to varying degrees, improvements in domains spanning physical, social and emotional functioning. Limitations of the current literature are identified; with particular emphasis on measurement and conceptual shortcomings. Suggestions are made in relation to improving the quality of future research, and how to further shed light on the impact of insomnia - and treatment thereof - on both HRQoL and global quality of life.

Heart rate and heart rate variability in subjectively reported insomnia

According to epidemiological studies, insomnia is associated with cardiovascular mortality. However, it is yet to be determined whether this link is mediated by known cardiovascular risk factors. The current study aimed at investigating the association between primary insomnia, defined as subjectively reported sleep disturbance in the absence of any other pathology or substance intake, and alterations in polysomnographically determined nocturnal heart rate (HR) and heart rate variability (HRV). A total of 4 581 nocturnal short‐term electrocardiographic recordings (5 min each) from 104 participants (58 with primary insomnia, 46 healthy controls) were evaluated for HR as well as for time and frequency domain measures of HRV. In the primary insomnia group, we found a lower wake‐to‐sleep HR reduction and a lower standard deviation of RR intervals (SDNN) compared to healthy controls. However, between‐group differences in resting HR were not found, and previous results of an increase in sympathovagal balance and a decrease in parasympathetic nocturnal activity in objectively determined insomnia could not be confirmed in our sample of self‐report insomnia patients. When restricting our analyses to insomnia patients with objectively determined short sleep duration, we found reduced parasympathetic activity as indicated by decreased high frequency power of HRV, as well as decreased root mean square of successive RRI differences (RMSSD) and percentage of successive RRIs that differ by more than 50 ms (pNN50) values. A lower wake‐to‐sleep HR reduction and alterations in HRV variables might, at least partially, mediate the increased rates of cardiovascular morbidity and mortality observed in insomnia patients.

...Not just a minor thing, it is something major, which stops you from functioning daily: quality of life and daytime functioning in insomnia.

According to diagnostic manuals, insomnia is a 24-hr disorder, impairing important aspects of daytime functioning. There is, however, little published work describing the impact of insomnia on important areas of functioning or, indeed, the experience of living with chronically disturbed sleep on a daily basis. This study recruited 11 volunteers with persistent insomnia to take part in 1 of 3 focus-group discussions, exploring the typical daytime consequences of poor sleep and impact on quality of life (QoL). A sub-sample (n = 8) were also asked to keep an audio-diary for 7 days—appraising sleep quality and subsequent daytime functioning. Interpretative phenomenological analysis (IPA) of transcripts produced 3 superordinate themes: “just struggle through,” “isolated, feeling like an outsider,” and “insomnia as an obstruction to the desired self.” Participants described daily difficulties with cognitive, emotional, and physical functioning; this had the cumulative effect of reducing work performance and social participation, as well as limiting life aspirations. Participants also described feeling isolated because of their disorder; this was precipitated by a lack of understanding from others and experiences with health care providers. Important novel data were generated on the proximal and distal impact of insomnia, indicating that chronically disturbed sleep can seriously limit overall QoL.

Genome-wide association analysis identifies novel loci for chronotype in 100,420 individuals from the UK Biobank.

Our sleep timing preference, or chronotype, is a manifestation of our internal biological clock. Variation in chronotype has been linked to sleep disorders, cognitive and physical performance, and chronic disease. Here we perform a genome-wide association study of self-reported chronotype within the UK Biobank cohort (n=100,420). We identify 12 new genetic loci that implicate known components of the circadian clock machinery and point to previously unstudied genetic variants and candidate genes that might modulate core circadian rhythms or light-sensing pathways. Pathway analyses highlight central nervous and ocular systems and fear-response-related processes. Genetic correlation analysis suggests chronotype shares underlying genetic pathways with schizophrenia, educational attainment and possibly BMI. Further, Mendelian randomization suggests that evening chronotype relates to higher educational attainment. These results not only expand our knowledge of the circadian system in humans but also expose the influence of circadian characteristics over human health and life-history variables such as educational attainment.

Sleep restriction therapy for insomnia is associated with reduced objective total sleep time, increased daytime somnolence, and objectively impaired vigilance: implications for the clinical management of insomnia disorder.

STUDY OBJECTIVES To investigate whether sleep restriction therapy (SRT) is associated with reduced objective total sleep time (TST), increased daytime somnolence, and impaired vigilance. DESIGN Within-subject, noncontrolled treatment investigation. SETTING Sleep research laboratory. PARTICIPANTS Sixteen patients [10 female, mean age = 47.1 (10.8) y] with well-defined psychophysiological insomnia (PI), reporting TST ≤ 6 h. INTERVENTIONS Patients were treated with single-component SRT over a 4-w protocol, sleeping in the laboratory for 2 nights prior to treatment initiation and for 3 nights (SRT night 1, 8, 22) during the acute interventional phase. The psychomotor vigilance task (PVT) was completed at seven defined time points [day 0 (baseline), day 1,7,8,21,22 (acute treatment) and day 84 (3 mo)]. The Epworth Sleepiness Scale (ESS) was completed at baseline, w 1-4, and 3 mo. MEASUREMENT AND RESULTS Subjective sleep outcomes and global insomnia severity significantly improved before and after SRT. There was, however, a robust decrease in PSG-defined TST during acute implementation of SRT, by an average of 91 min on night 1, 78 min on night 8, and 69 min on night 22, relative to baseline (P < 0.001; effect size range = 1.60-1.80). During SRT, PVT lapses were significantly increased from baseline (at three of five assessment points, all P < 0.05; effect size range = 0.69-0.78), returning to baseline levels by 3 mo (P = 0.43). A similar pattern was observed for RT, with RTs slowing during acute treatment (at four of five assessment points, all P < 0.05; effect size range = 0.57-0.89) and returning to pretreatment levels at 3 mo (P = 0.78). ESS scores were increased at w 1, 2, and 3 (relative to baseline; all P < 0.05); by 3 mo, sleepiness had returned to baseline (normative) levels (P = 0.65). CONCLUSION For the first time we show that acute sleep restriction therapy is associated with reduced objective total sleep time, increased daytime sleepiness, and objective performance impairment. Our data have important implications for implementation guidelines around the safe and effective delivery of cognitive behavioral therapy for insomnia.

The Sleep Condition Indicator: a clinical screening tool to evaluate insomnia disorder

Objective Describe the development and psychometric validation of a brief scale (the Sleep Condition Indicator (SCI)) to evaluate insomnia disorder in everyday clinical practice. Design The SCI was evaluated across five study samples. Content validity, internal consistency and concurrent validity were investigated. Participants 30 941 individuals (71% female) completed the SCI along with other descriptive demographic and clinical information. Setting Data acquired on dedicated websites. Results The eight-item SCI (concerns about getting to sleep, remaining asleep, sleep quality, daytime personal functioning, daytime performance, duration of sleep problem, nights per week having a sleep problem and extent troubled by poor sleep) had robust internal consistency (α≥0.86) and showed convergent validity with the Pittsburgh Sleep Quality Index and Insomnia Severity Index. A two-item short-form (SCI-02: nights per week having a sleep problem, extent troubled by poor sleep), derived using linear regression modelling, correlated strongly with the SCI total score (r=0.90). Conclusions The SCI has potential as a clinical screening tool for appraising insomnia symptoms against Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria.

The daytime impact of DSM-5 insomnia disorder: Comparative analysis of insomnia subtypes from the Great British Sleep Survey

OBJECTIVE To profile the daytime impact of the proposed DSM-5 insomnia disorder diagnosis, with and without mental health, physical health, or other sleep disorder comorbidities; to better understand how specific daytime symptom patterns are associated with nighttime sleep in insomnia; and to compare childhood-onset and adulthood-onset insomnia disorder with respect to daytime dysfunction. METHOD Data were derived from the Great British Sleep Survey (GBSS), an open-access online population survey completed by adults who had a valid postcode and were residents of the United Kingdom. The primary variables of interest were the 6 areas that, according to the proposed DSM-5 criteria, may be impacted in the daytime by insomnia disorder: energy, concentration, relationships, ability to stay awake, mood, and ability to get through work. These variables were compared for those with versus those without insomnia disorder and across 5 insomnia subtypes (difficulty initiating sleep, difficulty maintaining sleep, early morning awakening, a combination of these 3 core symptoms, or nonrestorative sleep). Clinically comorbid insomnia presentations (insomnia disorder with poor mental health/poor physical health/additional sleep disorder symptoms) and insomnia disorder of childhood versus adult onset were also evaluated. RESULTS A total of 11,129 participants (72% female; mean age = 39 years) completed the GBSS between March 2010 and April 2011, of whom 5,083 screened as having possible insomnia disorder. Compared with those who did not have insomnia disorder, those with insomnia disorder reported greater impairment in all areas of daytime functioning (Cohen d range, 0.68-1.30). The greatest effects reflected negative impact on energy and mood. Participants with a combination of insomnia symptoms tended to be the most impaired (Cohen d range, 0.10-0.23), whereas no consistent differences emerged between the other 4 subtypes. Finally, individuals who had both insomnia disorder and poor mental health were consistently the most impaired comorbid group (Cohen d range, 0.15-0.65), and childhood-onset insomnia disorder had greater daytime impact than adult-onset insomnia disorder (P < .05 for energy; P < .01 for mood, concentration, and getting through work). CONCLUSIONS The severity of daytime impact of DSM-5 insomnia disorder varies by insomnia type. This finding has implications for the evaluation and management of insomnia in clinical practice.

Genome-wide association analyses of sleep disturbance traits identify new loci and highlight shared genetics with neuropsychiatric and metabolic traits

Chronic sleep disturbances, associated with cardiometabolic diseases, psychiatric disorders and all-cause mortality, affect 25–30% of adults worldwide. Although environmental factors contribute substantially to self-reported habitual sleep duration and disruption, these traits are heritable and identification of the genes involved should improve understanding of sleep, mechanisms linking sleep to disease and development of new therapies. We report single- and multiple-trait genome-wide association analyses of self-reported sleep duration, insomnia symptoms and excessive daytime sleepiness in the UK Biobank (n = 112,586). We discover loci associated with insomnia symptoms (near MEIS1, TMEM132E, CYCL1 and TGFBI in females and WDR27 in males), excessive daytime sleepiness (near AR–OPHN1) and a composite sleep trait (near PATJ (INADL) and HCRTR2) and replicate a locus associated with sleep duration (at PAX8). We also observe genetic correlation between longer sleep duration and schizophrenia risk (rg = 0.29, P = 1.90 × 10−13) and between increased levels of excessive daytime sleepiness and increased measures for adiposity traits (body mass index (BMI): rg = 0.20, P = 3.12 × 10−9; waist circumference: rg = 0.20, P = 2.12 × 10−7).

The evidence base of sleep restriction therapy for treating insomnia disorder

Sleep restriction therapy is routinely used within cognitive behavioral therapy to treat chronic insomnia. However, the efficacy for sleep restriction therapy as a standalone intervention has yet to be comprehensively reviewed. This review evaluates the evidence for the use of sleep restriction therapy in the treatment of chronic insomnia. The literature was searched using web-based databases, finding 1344 studies. Twenty-one were accessed in full (1323 were deemed irrelevant to this review). Nine were considered relevant and evaluated in relation to study design using a standardized study checklist and levels of evidence. Four trials met adequate methodological strength to examine the efficacy of therapy for chronic insomnia. Weighted effect sizes for self-reported sleep diary measures of sleep onset latency, wake time after sleep onset, and sleep efficiency were moderate-to-large after therapy. Total sleep time indicated a small improvement. Standalone sleep restriction therapy is efficacious for the treatment of chronic insomnia for sleep diary continuity variables. Studies are insufficient to evaluate the full impact on objective sleep variables. Measures of daytime functioning in response to therapy are lacking. Variability in the sleep restriction therapy implementation methods precludes any strong conclusions regarding the true impact of therapy. A future research agenda is outlined.