The clinical effect of digital cognitive behavioural therapy for insomnia in subgroups with depressive and anxiety symptoms: A secondary analysis of a randomized-controlled trial.

Insomnia is a highly prevalent mental disorder, and is often co-occurring with depression and anxiety disorders. Cognitive behavioural therapy for insomnia as treatment of choice for insomnia can also be applied digitally (digital cognitive behavioural therapy for insomnia), making it more accessible. This is a secondary data analysis of a two-armed parallel randomized-controlled trial. In the primary publication, N = 238 participants meeting criteria for the 5th edition of Diagnostic and Statistical Manual of Mental Disorders chronic insomnia disorder were randomly assigned to either 8 weeks of digital cognitive behavioural therapy for insomnia + treatment-as-usual, or waitlist + treatment-as-usual. To determine the clinical effects of digital cognitive behavioural therapy for insomnia in populations with comorbid anxiety and depression symptoms, this secondary analysis focused on two subgroups: (1) participants with high initial depressive symptoms; and (2) participants with high initial anxiety symptoms. Symptoms of insomnia, depression and anxiety as primary outcome measures were obtained at baseline, 8 weeks post-randomization and, in the intervention group only, at 6- and 12-months follow-up. At 8 weeks post-randomization, the use of digital cognitive behavioural therapy for insomnia in both subgroups was associated with large reductions in insomnia severity in comparison to control (depression subgroup: d = 2.37; anxiety subgroup: d = 2.13). Between-group treatment effects were also observed for symptoms of depression in the depression subgroup (d = 1.59), and for symptoms of anxiety in the anxiety subgroup (d = 1.28). Within-group effects were stable over time (d = 0.64-1.63). This secondary analysis shows that digital cognitive behavioural therapy for insomnia reduces insomnia and comorbid symptoms in participants with high initial symptoms of either depression or anxiety with sustained long-term effects.

Clinical and cost-effectiveness of nurse-delivered sleep restriction therapy for insomnia in primary care (HABIT): a pragmatic, superiority, open-label, randomised controlled trial.

BACKGROUND: Insomnia is prevalent and distressing but access to the first-line treatment, cognitive behavioural therapy (CBT), is extremely limited. We aimed to assess the clinical and cost-effectiveness of sleep restriction therapy, a key component of CBT, which has the potential to be widely implemented. METHODS: We did a pragmatic, superiority, open-label, randomised controlled trial of sleep restriction therapy versus sleep hygiene. Adults with insomnia disorder were recruited from 35 general practices across England and randomly assigned (1:1) using a web-based randomisation programme to either four sessions of nurse-delivered sleep restriction therapy plus a sleep hygiene booklet or a sleep hygiene booklet only. There was no restriction on usual care for either group. Outcomes were assessed at 3 months, 6 months, and 12 months. The primary endpoint was self-reported insomnia severity at 6 months measured with the insomnia severity index (ISI). The primary analysis included participants according to their allocated group and who contributed at least one outcome measurement. Cost-effectiveness was evaluated from the UK National Health Service and personal social services perspective and expressed in terms of incremental cost per quality-adjusted life year (QALY) gained. The trial was prospectively registered (ISRCTN42499563). FINDINGS: Between Aug 29, 2018, and March 23, 2020 we randomly assigned 642 participants to sleep restriction therapy (n=321) or sleep hygiene (n=321). Mean age was 55·4 years (range 19-88), with 489 (76·2%) participants being female and 153 (23·8%) being male. 580 (90·3%) participants provided data for at least one outcome measurement. At 6 months, mean ISI score was 10·9 (SD 5·5) for sleep restriction therapy and 13·9 (5·2) for sleep hygiene (adjusted mean difference -3·05, 95% CI -3·83 to -2·28; p<0·0001; Cohen's d -0·74), indicating that participants in the sleep restriction therapy group reported lower insomnia severity than the sleep hygiene group. The incremental cost per QALY gained was £2076, giving a 95·3% probability that treatment was cost-effective at a cost-effectiveness threshold of £20 000. Eight participants in each group had serious adverse events, none of which were judged to be related to intervention. INTERPRETATION: Brief nurse-delivered sleep restriction therapy in primary care reduces insomnia symptoms, is likely to be cost-effective, and has the potential to be widely implemented as a first-line treatment for insomnia disorder. FUNDING: The National Institute for Health and Care Research Health Technology Assessment Programme.

The clinical effects of digital cognitive behavioral therapy for insomnia in a heterogenous study sample: results from a randomized controlled trial.

STUDY OBJECTIVES: Numerous studies worldwide have reported the beneficial effects of digital cognitive behavioral therapy for insomnia (dCBT-I). However, few focus on real-world study samples that reflect people in regular care. To test whether dCBT-I is suitable within German regular care, we designed a randomized controlled trial recruiting a heterogenous insomnia population. METHODS: Participants aged ≥18 who met the criteria for insomnia disorder were randomized to 8-weeks dCBT-I + care-as-usual (CAU) or they were set on a waitlist + CAU. The intervention group was followed-up at 6- and 12-months. The primary outcome was self-reported insomnia severity, assessed with the Insomnia Severity Index (ISI) at 8-weeks post-randomization. A one-way ANCOVA with baseline score as a covariate was fitted to determine group differences. Secondary outcomes included measures of daytime functioning, quality of life, depression, anxiety, dreams, and nightmares. RESULTS: Of the N = 238 participants (67.6% female), age range 19-81 years, n = 118 were randomized to dCBT-I and n = 120 to the control group. At posttreatment, the use of dCBT-I was associated with a large reduction in the ISI (Diffadj = -7.60) in comparison to WLC (d = -2.08). This clinical improvement was also reflected in responder and remission rates. Treatment effects were also observed for daytime functioning, quality of life, symptoms of depression and anxiety (ds = 0.26-1.02) and at long-term follow-up (intervention group only; ds = 0.18-1.65). No effects were found for dream and nightmare frequency. CONCLUSIONS: This study showed that dCBT-I reduces insomnia symptoms and improves daytime functioning in a heterogenous insomnia population in Germany with sustained long-term treatment effects in the intervention group. Our results underscore the potential of digital health applications, their suitability within regular care, and their role in facilitating widespread implementation of CBT-I as a first-line treatment for insomnia.

The effect of sleep restriction therapy for insomnia on sleep pressure and arousal: a randomized controlled mechanistic trial.

STUDY OBJECTIVES: Sleep restriction therapy (SRT) effectively treats insomnia but mechanisms are poorly understood. Theoretical models suggest that potentiation of sleep pressure and reduction of arousal are key mechanisms of action. To our knowledge, this has never been directly tested. We designed a randomized controlled trial with embedded mechanistic measurement to investigate if SRT causally modifies multidimensional assessments of sleep pressure and arousal. METHODS: Participants aged 25-55 who met DSM-5 diagnostic criteria for insomnia disorder were randomized to four weeks of SRT or time in bed regularization (TBR), a control intervention that involves prescription of a regular but not reduced time in bed. Sleep pressure was assessed through daily diary appraisal of morning and evening sleepiness, weekly Epworth sleepiness scale (ESS) scores, psychomotor vigilance, and non-rapid eye movement (NREM) delta power (0.75-4.5 Hz) from ambulatory polysomnographic recordings. Arousal was assessed through daily diary appraisal of cognitive arousal, the pre-sleep arousal scale (PSAS), and NREM beta power (15-32 Hz). Outcomes were assessed at baseline (2-week period prior to randomization), during the intervention phase (1-4 weeks post-randomization), and at 12-week follow-up. We performed intention-to-treat analyses using linear mixed models. For continuous daily measures, the treatment period was split into early (weeks 1-2) and late (weeks 3-4) treatment. RESULTS: Fifty-six participants (39 females, mean age = 40.78 ± 9.08) were assigned to SRT (n = 27) or TBR (n = 29). The SRT group showed enhanced sleep pressure relative to TBR, reflected in (1) enhanced sleepiness in the evening during early (d = 1.17) and late treatment (d = 0.92), and in the morning during early treatment (d = 0.47); (2) higher daytime sleepiness on the ESS at weeks-1 and -2 (d = 0.54, d = 0.45); and (3) reduced psychomotor vigilance at week-1 (d = 0.34). The SRT group also showed reduced arousal relative to TBR, reflected in lower levels of daily-monitored cognitive arousal during early treatment (d = 0.53) and decreased PSAS total score at week-4 and week-12 (ds ≥ 0.39). Power spectral analysis of all night NREM sleep revealed an increase in relative, but not absolute, EEG delta power at week-1 and week-4 (ds ≥ 0.52) and a decrease of relative EEG beta power at week-4 (d = 0.11). CONCLUSION: For the first time, we show that SRT increases sleep pressure and decreases arousal during acute implementation, providing support for mechanism-of-action.

The clinical effects of sleep restriction therapy for insomnia: A meta-analysis of randomised controlled trials.

Sleep restriction therapy (SRT) is an established treatment for insomnia that has been used in clinical practise for over 30 y. It is commonly delivered as part of multicomponent cognitive-behavioural therapy (CBT-I) but has also been linked to beneficial effects as a standalone intervention. In order to quantify the efficacy of SRT we performed a comprehensive meta-analysis of randomised controlled trials (RCTs) comparing SRT to minimally active or non-active control groups. Primary outcomes were self-reported insomnia severity and sleep diary metrics at post-treatment. Weighted effect sizes were calculated with Hedges' g and risk of bias was assessed by two independent raters with the Cochrane tool. Our search yielded eight RCTs meeting inclusion/exclusion criteria. Random effects models revealed large treatment effects in favour of SRT versus control for insomnia severity measured with the insomnia severity index (g = -0.93; 95% CI = -1.15, -0.71), sleep efficiency (g = 0.91; 95% CI = 0.52, 1.31), sleep onset latency (g = -0.62; 95% CI = -0.84, -0.40), and wake-time after sleep onset (g = -0.83; 95% CI = -1.11, -0.55). No effects were found for total sleep time (g = 0.02; 95% CI = -0.29, 0.34). Results should be interpreted in the context of the small number of comparisons (≤6 per outcome), high risk of bias (6 out of 8 studies met criteria for high risk), and heterogeneity in study design and SRT administration. Only a small number of studies provided outcomes at follow-up (n ≤ 3), hindering assessment of long-term effects. Sleep restriction therapy effectively improves insomnia severity and sleep continuity in the short term; more studies are needed to assess if effects are sustained at long-term follow-up (>3 m). Post-treatment effect sizes appear as large as multicomponent CBT-I. To reduce risk of bias, future studies should consider testing the effects of SRT against control groups that are matched for non-specific treatment effects. Large-scale pragmatic trials are also needed to test if SRT is effective in clinical practise and to quantify effects on daytime functioning and quality of life.

Reporting of adverse events in cognitive behavioural therapy for insomnia: A systematic examination of randomised controlled trials.

Adverse events are undesirable events that can occur during medical or psychological treatment. There has been limited attention to adverse events in psychological treatment trials relative to pharmacotherapy trials. Cognitive behavioural therapy (CBTI) is the first line treatment for insomnia but studies have reported potential negative effects during acute implementation. This review aimed to understand the extent to which adverse events are monitored for and reported in the CBTI trial literature. Ninety-nine randomised controlled trials were identified for inclusion, with findings showing that 32.3% (n = 32) of studies addressed adverse events in some way, while only 7.1% (n = 7) of studies met all criteria for adequate reporting of adverse events. For studies that reported on adverse events by group, there did not appear to be consistent differences between trial arms, however the limited evidence-base coupled with marked heterogeneity in monitoring and reporting makes it difficult to draw clear conclusions at this time. We outline recommendations for the field aimed at improving prospective monitoring and reporting of adverse events in psychological/behavioural treatment trials.

The acute effects of sleep restriction therapy for insomnia on circadian timing and vigilance.

Sleep-restriction therapy (SRT) has been shown to improve insomnia symptoms by restricting sleep opportunity. Curtailment of time in bed affects the duration and consolidation of sleep, but also its timing. While recent work suggests that people with insomnia are characterised by misalignment between circadian and behavioural timing of sleep, no study has investigated if SRT modifies this relationship. The primary aim of the present study was to examine change in phase angle after 2 weeks of SRT. As a secondary aim, we also sought to assess the effect of SRT on psychomotor vigilance. Following a 1-week baseline phase, participants implemented SRT for 2 consecutive weeks. Phase angle was derived from the difference between the decimal clock time of dim light melatonin onset (DLMO) and attempted sleep time. Secondary outcomes included vigilance (assessed via hourly measurement during the DLMO laboratory protocol), sleep continuity (assessed via sleep diary and actigraphy), and insomnia severity. Eighteen participants meeting insomnia criteria (mean [SD] age 37.06 [8.99] years) took part in the study. Consistent with previous research, participants showed robust improvements in subjective and objective sleep continuity, as well as reductions in insomnia severity. The primary outcome (phase angle) was measurable in 15 participants and revealed an increase of 34.8 min (~0.58 hr; 95% confidence interval [CI] 0.01-1.15) from baseline to post-treatment (mean [SD] 2.27 [0.94] versus 2.85 [1.25] hr). DLMO remained relatively stable (20:49 versus 21:01 hours), while attempted sleep was 46.8 min later (~0.78 hr; 95%CI 0.41-1.15; 23:05 versus 23:52 hours). For psychomotor vigilance, reaction time was delayed (by 52.71 ms, 95% CI 34.44-70.97) and number of lapses increased (by 5.84, 95% CI 3.93-7.75) after SRT. We show that SRT increases phase angle during treatment, principally by delaying the timing of sleep attempt. Future studies are needed to test if an increase in phase angle is linked to clinical improvement. Finally, reduction in vigilance after SRT appears to be of similar magnitude to normal sleepers undergoing experimental sleep restriction, reinforcing the importance of appropriate safety advice during implementation.

How does sleep restriction therapy for insomnia work? A systematic review of mechanistic evidence and the introduction of the Triple-R model.

For over 30 y sleep restriction therapy (SRT) has been used to treat insomnia but we know very little about how this therapy exerts its effects. When SRT was first described, it was hypothesised to treat insomnia by addressing four key factors: strengthening homeostatic sleep pressure, inhibiting perpetuating practices (excessive time in bed), attenuating hyperarousal and tightening regulatory control of sleep by the endogenous circadian pacemaker. We conducted a systematic literature review in search of evidence for these putative mechanisms-of-action. A total of 15 randomised and non-randomised studies investigating SRT met inclusion criteria. For each study, we extracted all variables associated with the proposed mechanisms and assessed study quality using a structured appraisal tool. The extracted variables were: time in bed (TIB), napping, variability in sleep, markers of circadian rhythmicity, measurements of sleep pressure/sleepiness, and assessments of arousal. Overall study quality was poor as indicated by a mean quality score of 17 (out of a possible range of 0-31). No study indicated, or indeed was designed to test, whether changes in the proposed mechanisms act as mediators of treatment outcomes. Of all reviewed studies, most reported a reduction in TIB (10/10) and/or revealed a decrease in sleep onset latency (10/14), indexing increased sleep pressure. However, such changes were most often reported at the end of treatment, reflecting an outcome and not a mechanism of SRT per se. Evidence for reduction in arousal (4/4) and night-to-night sleep variability (2/2) was found in only a small number of uncontrolled studies while there was no evidence for change in circadian phase or periodicity (0/1). Our review suggests that SRT targets some of the hypothesised processes but specifically-designed mechanistic evaluations are needed. We introduce a new testable model of SRT mechanism-of-action (Triple-R) and set out a research agenda aimed at stimulating prospective investigations.