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

12009 Background: Women on chemotherapy for breast cancer (BC) report high levels of insomnia and fatigue. This trial aimed to test the main effects of Cognitive Behavioral Therapy for Insomnia (CBT-I) and Bright Light Therapy (BLT) on insomnia and fatigue symptoms. Methods: This multi-center, randomized, controlled, 2 x 2 factorial, superiority, trial enrolled 219 women receiving cytotoxic chemotherapy for any stage BC. Interventions were: (1) neither CBT-I nor BLT (sleep hygiene education; SHE), (2) BLT, (3) CBT-I, and (4) BLT+CBT-I. The 6-week interventions included one telehealth, 1:1 session followed by emails and a mid-treatment call. Assessments occurred at baseline, 3 and 6 weeks. Dual primary outcomes were the insomnia severity index (ISI) and PROMIS Fatigue. Intention-to-treat analyses were latent growth models. Effect sizes are standardized mean differences (SMDs). Results: Mean age was 50.7y and 24% had metastatic cancer. At baseline, average ISI was 13.24 (SD = 5.48; sub-threshold insomnia), and fatigue was 59.57 (SD = 7.91; moderate fatigue). 88% (n = 198) completed the telehealth session. 75% (n = 165) reported post-treatment outcomes. ISI and fatigue decreased in all conditions (see Table). CBT-I improved ISI (mean difference = -2.03; p = .001; SMD = -0.37), but BLT did not (mean difference = -1.09; p = .082; SMD = -0.20). Neither intervention affected fatigue (SMDs -0.06 to -0.07; p > 0.60). There was no BLTxCBT-I interaction for ISI nor fatigue ( p > 0.50). Conclusions: In patients receiving chemotherapy for BC, brief CBT-I can improve insomnia but not fatigue symptoms. BLT did not improve insomnia or fatigue. We found no evidence of an interaction between BLT and CBT-I. During chemotherapy, fatigue may not be responsive to brief sleep and circadian-oriented treatments. Clinical trial information: ACTRN12620001133921 . Between group (main effects) and within group (change). ISI [95% CI] P, SMD Fatigue [95% CI] P, SMD Main Effects BLT -1.09 [-2.31, 0.14] p = .082, SMD = -0.20 -0.49 [-2.87, 1.88] p = .68, SMD = -0.06 CBT-I -2.03 [-3.25, -0.81] p = .001, SMD = -0.37 -0.54 [-2.92, 1.83] p = .65, SMD = -0.07 Change: 0–6 weeks SHE -3.41 [-4.65, -2.17] p < .001, SMD = -0.62 -3.75 [-6.16, -1.34] p = .002, SMD = -0.47 BLT -4.89 [-6.12, -3.66] p < .001, SMD = -0.89 -3.75 [-6.13, -1.37] p = .002, SMD = -0.47 CBT-I -5.83 [-7.12, -4.54] p < .001, SMD = -1.06 -3.80 [-6.30, -1.31] p = .003, SMD = -0.48 CBT-I+BLT -6.53 [-7.88, -5.18] p < .001, SMD = -1.19 -4.79 [-7.44, -2.14] p < .001, SMD = -0.61

This study aimed to assess the effectiveness of cognitive behavioral therapy for insomnia (CBTI) during the postpartum period as part of a larger randomized controlled trial of CBTI on perinatal insomnia. A total of 179 women of 18-30 gestational weeks with insomnia disorder were randomly assigned to CBTI or an active control (CTRL) therapy. Participants were assessed between 18 and 32 weeks of pregnancy at baseline, after the intervention during pregnancy, and at 8, 18, and 30 weeks postpartum. The primary outcomes were Insomnia Severity Index (ISI) scores and total awake time, defined as minutes awake during the sleep opportunity period, assessed with actigraphy and sleep diaries. Included in the analyses were women who provided data for at least 1 of 3 postpartum assessments (68 in CBTI; 61 in CTRL). Piecewise mixed-effects models revealed a main effect reflecting reduction in ISI scores from 8-18 weeks postpartum (P = .036) and a nonsignificant increase from 18-30 weeks; significant effects for group allocation were present only in week 30 (P = .042). CTRL participants reported significantly longer time awake, excluding time spent caring for the infant, at each postpartum assessment; time awake at night caring for the infant did not differ between groups. There was no significant group difference in the postpartum trajectory of actigraphy-measured total awake time, the two diary measures of time awake (P values > .05). CBTI participants with at least 50% reduction in ISI during pregnancy had consistently stable ISI scores (mean < 6) during the postpartum period; those in the CTRL group had variable ISI scores over time with large individual differences. For women with insomnia disorder during pregnancy, CBTI initiated during pregnancy conferred postpartum benefits in terms of wakefulness after sleep onset (excluding time spent caring for the infant) and insomnia severity, though the latter emerged only later in the postpartum period. These findings underscore the importance of treating insomnia during pregnancy, a conclusion that is further supported by our finding that pregnant women who responded to insomnia treatment during pregnancy experienced better sleep in the postpartum period. Registry: Clinicaltrials.gov; Name: Treatment for Insomnia During Pregnancy; URL: https://www.clinicaltrials.gov/ct2/show/NCT01846585; Identifier: NCT01846585. Manber R, Bei B, Suh S, etal. Randomized controlled trial of cognitive behavioral therapy for perinatal insomnia: postpartum outcomes. J Clin Sleep Med. 2023;19(8):1411-1419.

Objective To compare the effectiveness of protocols for acceptance and commitment therapy for insomnia (ACT-I) and cognitive behavioral therapy for insomnia (CBT-I) in adults. Method Participants were 37 adults (74.3% women; M = 43.7 years, SD = 10.7) with chronic insomnia who were randomized to 6 weekly group sessions consisting of ACT-I (n = 19) or CBT-I (n = 18). The primary outcome measures were based on the Insomnia Severity Index (ISI) total score, a measure of insomnia complaints, and included the proportions of treatment responders (defined as a change in score of 8 points or more) and remitters (defined as a final score below 8). Results Both treatment modalities significantly reduced insomnia severity. Post-treatment, the proportion of treatment responders was higher in the CBT-I than the ACT-I (64.7% vs. 50.0%, respectively) group and six months later, ACT-I made further improvements whereas CBT-I had a reduced treatment response (58.8% vs. 55.6%, respectively). CBT-I was associated with a higher proportion of insomnia remission at post treatment. Conclusions Both CBT-I and ACT-I are effective, with a higher proportion of insomnia remitters in CBT-I post-treatment. The different change trajectories for the two therapy groups provide insights into behavioral change via a cognitive versus contextual approach.

Insomnia is a distressing and often persisting consequence of cancer. Although cognitive behavioral therapy for insomnia (CBT-I) is the treatment of choice in the general population, the use of CBT-I in patients with cancer is complicated, because it can result in transient but substantial increases in daytime sleepiness. In this study, we evaluated whether CBT-I, in combination with the wakefulness-promoting agent armodafinil (A), results in better insomnia treatment outcomes in cancer survivors than CBT-I alone. We report on a randomized trial of 96 cancer survivors (mean age, 56 years; female, 87.5%; breast cancer, 68%). The primary analyses examined whether ≥ one of the 7-week intervention conditions (ie, CBT-I, A, or both), when compared with a placebo capsule (P) group, produced significantly greater clinical gains. Insomnia was assessed by the Insomnia Severity Index and sleep quality by the Pittsburgh Sleep Quality Inventory. All patients received sleep hygiene instructions. Analyses controlling for baseline differences showed that both the CBT-I plus A (P = .001) and CBT-I plus P (P = .010) groups had significantly greater reductions in insomnia severity postintervention than the P group, with effect sizes of 1.31 and 1.02, respectively. Similar improvements were seen for sleep quality. Gains on both measures persisted 3 months later. CBT-I plus A was not significantly different from CBT-I plus P (P = .421), and A alone was not significantly different from P alone (P = .584). CBT-I results in significant and durable improvements in insomnia and sleep quality. A did not significantly improve the efficacy of CBT-I or independently affect insomnia or sleep quality.

Treat Chronic Insomnia With CBT-I, Says American College of Physicians

Insomnia and depression are highly co-morbid conditions that share a complex, bi-directional relationship. By reviewing the literature examining the links between insomnia and depression, it becomes apparent that insomnia symptoms need to be directly targeted alongside depression symptoms when co-morbidities exist for optimal outcomes. The most common treatment in Australia for co-morbid insomnia and depression is currently antidepressant medication. Because a large percentage of individuals given antidepressants fail to remit from their depression and insomnia symptoms, an effective adjunct treatment to antidepressants for co-morbid insomnia and depression is required. Cognitive behavioural therapy for insomnia (CBT-I) is an empirically validated treatment for insomnia, and is efficacious in improving insomnia that is co-morbid with depression. Recent evidence also suggests that CBT-I produces significant improvements in depression severity. The main aim of the thesis was therefore to develop a cost-effective CBT-I intervention that could be easily administered, distributed and implemented on a wide-scale basis, both on its own for insomnia, and primarily as an adjunct therapy for co-morbid insomnia and depression. A therapist manual of CBT-I, based on the latest empirical findings, was specifically developed to increase consistency and ease of treatment administration by therapists wanting to deliver CBT-I treatment. A resource booklet was also developed to give to all individuals undergoing CBT-I treatment, to ensure that they were provided with the latest information about sleep and how to reduce their insomnia severity. A randomised controlled trial was then developed to investigate the efficacy of this CBT-I intervention in individuals with co-morbid insomnia and depression whose symptoms have failed to remit through antidepressant treatment. Forty-one participants (aged 18-64 years) were randomized to receive four sessions of either CBT-I or sleep education (self-help therapy) over an 8-week period (one session every two weeks). Participants had been treated with antidepressants for at least six weeks prior to screening, but were otherwise healthy. The Insomnia Severity Index and the Beck Depression Inventory were assessed at baseline, following each session, and at 3-month follow-up. Secondary outcomes were sleep quality and duration (actigraphy and self-report), anxiety, fatigue, and daytime sleepiness. Results indicated that CBT-I, compared to sleep education, produced significantly reduced depression and insomnia severity, and improved anxiety, fatigue, sleep quality and sleep efficiency. It is the first randomised controlled trial of CBT-I for co-morbid insomnia and depression, with an active control treatment, to show significant reductions in both insomnia and depression severity at post-treatment and follow-up. Large effect sizes were found for both insomnia and depression at post-treatment, and these effect sizes increased further by three month follow-up. At follow-up, ten times more CBT-I participants were in remission from both insomnia and depression than sleep education participants. This demonstrates that CBT-I is an efficacious treatment for co-morbid insomnia and depression, and should be considered an important adjunct therapy in individuals whose symptoms have not remitted through antidepressant treatment. Following the positive results of the randomised controlled trial, the proposed mediators of CBT-I were examined to determine which aspects of the intervention had the largest influence on reductions in insomnia and depression severity at post-treatment and 3-month follow-up. Changes in time-in-bed, bedtime variability, rise-time variability, sleep hygiene practices, dysfunctional beliefs about sleep and stress levels were assessed as potential mediators. Post-treatment results indicated that the significantly reduced depression severity through CBT-I was primarily via reduced stress levels, improved sleep hygiene practices, and other therapeutic effects of CBT-I, whereas reduced insomnia severity was primarily via reduced dysfunctional beliefs about sleep. By follow-up, the significantly reduced depression severity in the CBT-I group was primarily via reduced stress levels and reduced dysfunctional beliefs about sleep, whereas reduced dysfunctional beliefs about sleep and other therapeutic effects of CBT-I explained the significantly reduced insomnia severity. These results indicate that reducing stress levels through CBT-I treatment is required for optimal depression outcomes, whereas reducing dysfunctional beliefs about sleep is essential for optimal insomnia outcomes. Improving sleeping practices behaviourally is important for initial depression improvements, but reducing dysfunctional beliefs about sleep becomes more important for longer-term remission of depression symptoms. Other non-factual therapeutic elements of CBT-I treatment appear to be important, and may lead to a greater willingness to engage in the CBT-I strategies, which can improve depression in the short-term and insomnia in the longer-term. These mediators of CBT-I treatment had not been specifically examined in individuals with co-morbid insomnia and depression before this study. Their identification suggests that relaxation and behavioural sleep interventions should be prioritized initially through CBT-I for co-morbid insomnia and depression, followed by cognitive interventions to target unhelpful beliefs about sleep. By increasing the efficiency of CBT-I, optimal treatment outcomes can be achieved for individuals with co-morbid insomnia and depression, and the risk of future relapse can be minimized.

This study examines the impact of cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) therapy for comorbid insomnia and sleep apnea on nocturnal sleep and daytime functioning. A partial factorial design was used to examine treatment pathways with CBT-I and PAP and the relative benefits of each treatment. One hundred eighteen individuals with comorbid insomnia and sleep apnea were randomized to receive CBT-I followed by PAP, self-monitoring followed by CBT-I concurrent with PAP, or self-monitoring followed by PAP only. Participants were assessed at baseline, PAP titration, and 30 and 90 days after PAP initiation. Outcome measures included sleep diary- and actigraphy-measured sleep, Flinders Fatigue Scale, Epworth Sleepiness Scale, Functional Outcome of Sleep Questionnaire, and cognitive emotional measures. A main effect of time was found on diary-measured sleep parameters (decreased sleep onset latency and wake after sleep onset; increased total sleep time and sleep efficiency) and actigraphy-measured sleep parameters (decreased wake after sleep onset; increased sleep efficiency) and daytime functioning (reduced Epworth Sleepiness Scale, Flinders Fatigue Scale; increased Functional Outcome of Sleep Questionnaire) across all arms (all P < .05). Significant interactions and planned contrast comparisons revealed that CBT-I was superior to PAP and self-monitoring on reducing diary-measured sleep onset latency and wake after sleep onset and increasing sleep efficiency, as well as improving Functional Outcome of Sleep Questionnaire and Flinders Fatigue Scale compared to self-monitoring. Improvements in sleep and daytime functioning were found with PAP alone or concomitant with CBT-I. However, more rapid effects were observed on self-reported sleep and daytime performance when receiving CBT-I regardless of when it was initiated. Therefore, concomitant treatment appears to be a favorable approach to accelerate treatment outcomes. Registry: ClinicalTrials.gov; Name: Multidisciplinary Approach to the Treatment of Insomnia and Comorbid Sleep Apnea (MATRICS); URL: https://clinicaltrials.gov/ct2/show/NCT01785303; Identifier: NCT01785303. Tu AY, Crawford MR, Dawson SC, etal. A randomized controlled trial of cognitive behavioral therapy for insomnia and PAP for obstructive sleep apnea and comorbid insomnia: effects on nocturnal sleep and daytime performance. J Clin Sleep Med. 2022;18(3):789-800.

Effectiveness of cognitive behavioral therapy for pharmacotherapy-resistant chronic insomnia: a multi-center randomized controlled trial in Japan

BackgroundInsomnia is common in people with long-term medical conditions and is related to increased mortality and morbidity. Cognitive behavioral therapy for insomnia (CBT-I) is first choice treatment and effective for people with insomnia and comorbid long-term medical conditions. However, CBT-I has some limitations as it might not always be available or appeal to patients with medical conditions. Furthermore, a small proportion of patients do not respond to CBT-I. Preliminary evidence and clinical experience suggest that low-dose amitriptyline (AM) might be an effective alternative to treat insomnia in patients with medical comorbidity. In this randomized controlled trial, we will determine whether AM is non-inferior to the first choice treatment for insomnia, CBT-I.Methods/designThis study will test if treatment with low-dose amitriptyline for insomnia in patients with medical comorbidity is non-inferior to CBT-I in a multicenter randomized controlled non-inferiority trial. Participants will be 190 adults with a long-term medical condition and insomnia. Participants will be randomly allocated to one of two intervention arms: 12 weeks AM (starting with 10 mg per day, and if ineffective at 3 weeks, doubling this dose) or 12 weeks of CBT-I consisting of 6 weekly sessions and a follow-up session 6 weeks later. The primary outcome is subjective insomnia severity, measured with the Insomnia Severity Index (ISI). The primary endpoint is at 12 weeks. Secondary outcomes include sleep quality (e.g., sleep efficiency), questionnaires on daytime functioning (physical functioning and impairment of functioning), and symptoms (e.g., fatigue, pain, anxiety) at 12 weeks and 12 months post treatment and relapse of insomnia until 12 months after treatment.DiscussionIrrespective of the outcome, this study will be a much-needed contribution to evidence based clinical guidelines on the treatment of insomnia in patients with medical comorbidity.Trial registrationDutch Trial Register NTR NL7971. Registered on 18 August 2019

Osteoarthritis-related insomnia is the most common form of comorbid insomnia among older Americans. A randomized clinical trial found that six sessions of telephone-delivered cognitive behavioral therapy for insomnia (CBT-I) improved sleep outcomes in this population. Using these data, we evaluated the incremental cost-effectiveness of CBT-I from a healthcare sector perspective. The study was based on 325 community-dwelling older adults with insomnia and osteoarthritis pain enrolled with Kaiser Permanente of Washington State. We measured quality-adjusted life years (QALYs) using the EuroQol 5-dimension scale. Arthritis-specific quality of life was measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Insomnia-specific quality of life was measured using the Insomnia Severity Index (ISI) and nights without clinical insomnia (i.e., "insomnia-free nights"). Total healthcare costs included intervention and healthcare utilization costs. Over the 12 months after randomization, CBT-I improved ISI and WOMAC by -2.6 points (95% CI: -2.9 to -2.4) and -2.6 points (95% CI: -3.4 to -1.8), respectively. The ISI improvement translated into 89 additional insomnia-free nights (95% CI: 79 to 98) over the 12 months. CBT-I did not significantly reduce total healthcare costs (-$1072 [95% CI: -$1968 to $92]). Improvements in condition-specific measures were not reflected in QALYs gained (-0.01 [95% CI: -0.01 to 0.01]); at a willingness-to-pay of $150,000 per QALY, CBT-I resulted in a positive net monetary benefit of $369 with substantial uncertainty (95% CI: -$1737 to $2270). CBT-I improved sleep and arthritis function without increasing costs. These findings support the consideration of telephone CBT-I for treating insomnia among older adults with comorbid OA. Our findings also suggest potential limitations of the general quality of life measures in assessing interventions designed to improve sleep and arthritis outcomes.

Introduction Disordered circadian rest/activity rhythms (RARs) and insomnia frequently co-occur. Aspects of cognitive behavioral therapy for insomnia (CBTI) aim at improving circadian RARs by establishing regular sleep times and consolidating sleep periods. Timing of sleep periods has also been associated with insomnia, wherein evening chronotype has been linked to greater sleep disturbance. However, there is limited research exploring whether CBTI improves insomnia via improved structure and timing of circadian RARs. We examined whether CBTI reduces insomnia severity via improved RAR structure or shifted RAR timing. Methods Our community sample of persons with a history of traumatic brain injury (TBI) and comorbid insomnia (N=38, Mage=38+/-12, 37% female) were randomized to a 4-session treatment group: CBTI or sleep education. Circadian RARs were continually estimated with actigraphy. Variables estimating RAR structure included interdaily stability (IS), intradaily variability (IV), and relative amplitude (RA). RAR timing was estimated as the sleep period midpoint. Effects of CBTI on RAR variables were estimated as the group difference in change in RAR variables from baseline to treatment end. Effect of CBTI on insomnia severity was estimated as the group difference in Insomnia Severity Index (ISI) score change from baseline to 12-weeks post-treatment. Secondary analyses explored whether RAR change moderated effects of treatment group on ISI change. Results Compared to controls, participants randomized to CBTI had improved long-term ISI scores (β= -0.851, SE=0.322, p=0.008). CBTI had no effect on change in sleep midpoint, IV, RA, or IS. However, a significant IV by group interaction suggested that individuals with greater reduction in sleep-wake rhythm fragmentation during CBTI experienced greater reduction in insomnia severity (β= -0.894, SE=0.401, p=0.026). Conclusion Results show that CBTI reduced insomnia severity. While CBTI did not affect IV, RA, IS, or the sleep midpoint, CBTI-induced reductions in insomnia severity were stronger in those who exhibited greater reductions in IV. This suggests that benefits of CBTI may be influenced by changes in RARs in those with TBI. Future analyses will explore factors associated with changes in circadian rhythm and insomnia severity, and examine CBTI effects on circadian rhythm and sleep phase in a larger sample. Support (if any) AASM Foundation Strategic Research Grant Category I.

Introduction Insomnia is often comorbid with depression in youths and both may reciprocally exacerbate clinical outcomes and lead to a constellation of detrimental consequences. The present study aimed to test the efficacy of cognitive behavioral therapy (CBT) for insomnia (CBT-I) and CBT for depression (CBT-D), when compared with waitlist control, in youths with comorbid insomnia and depression. Methods 112 participants aged 12–24 years old (67.9% female) with insomnia and depression according to DSM-5 diagnostic criteria were randomised to one of the following conditions: 8-week group CBT-I (n=33), 8-week group CBT-D (n=39), or waiting-list control (n=40). Insomnia (Insomnia Severity Index, ISI) and depressive symptoms (Hamilton Rating Scale for Depression, HAMD) were assessed at baseline and post-intervention. The two active treatment groups were additionally followed up at post-treatment one-month. Results Linear mixed model showed that both treatment groups (CBT-D: Cohen’s d = -0.44, p&amp;lt;.001; CBT-I: Cohen’s d =-0.56, p&amp;lt;.001) had significantly lower ISI scores at post-intervention follow-up, as compared to the waitlist group. There was a significant difference in clinically meaningful improvement in insomnia (a reduction of ISI score ≥ 6 from baseline to post-intervention follow-up) between the groups (CBT-I: 73.1%; CBT-D: 40.0%; WL: 28.6%; p=.002). Moreover, there was a significant difference in remission of depression (HAMD≤7) at post-intervention follow-up (CBT-D: 75.9%; CBT-I: 81.5%; WL: 22.9%) (p &amp;lt;.001). Both CBT-D and CBT-I resulted in comparable improvements in insomnia and depressive symptoms at one-month follow-up (p&amp;gt;.05). Conclusion Preliminary evidence from this study supports the efficacy of CBT-I for improving both sleep and mood in youths with comorbid insomnia and depression. Support (if any) This work was supported by Early Career Scheme, Research Grants Council, Hong Kong SAR (Ref. 27613017).

TMS and CBT-I for comorbid depression and insomnia. Exploring feasibility and tolerability of transcranial magnetic stimulation (TMS) and cognitive behavioral therapy for insomnia (CBT-I) for comorbid major depressive disorder and insomnia during the COVID-19 pandemic

Study objectivesIn a randomized controlled non-inferiority trial, we aimed to determine whether low-dose amitriptyline, which is often used off-label, is a safe and effective alternative to cognitive behavioral therapy for insomnia in the treatment of insomnia among patients with insomnia and medical comorbidity.MethodsA total of 187 participants with insomnia and medical comorbidity were randomly allocated to either: (1) 12 weeks of amitriptyline, 10–20 mg (n = 93), or (2) 12 weeks of group cognitive behavioral therapy for insomnia, seven sessions (n = 94). Assessments took place at baseline, 6 and 12 weeks after start of treatment. The primary non-inferiority outcome was insomnia severity (Insomnia Severity Index) at 12 weeks.ResultsBased on a non-inferiority margin of four points on the Insomnia Severity Index, amitriptyline was non-inferior to cognitive behavioral therapy for insomnia at 12 weeks of treatment (mean difference of 1.1 points; 95% confidence interval = −0.5 to 2.8). Secondary analyses showed that significantly more cognitive behavioral therapy for insomnia participants reached a clinical response (≥eight-point reduction on the Insomnia Severity Index) than amitriptyline participants (58 per cent versus 41 per cent, p = .02). Amitriptyline participants reported more side effects (mostly anticholinergic) at 12 weeks treatment (p < .001) than participants who received cognitive behavioral therapy for insomnia. After discontinuation 68 per cent of the amitriptyline participants reported worsening of sleep. In 12 per cent of them this worsening was temporarily.ConclusionsWith a liberal non-inferiority margin, amitriptyline is non-inferior to cognitive behavioral therapy for insomnia in reducing insomnia severity. Amitriptyline has more side effects and its effect on insomnia may diminish after tapering. Cognitive behavioral therapy for insomnia should remain first-line treatment for patients with medical comorbidity given its broader benefits.Statement of SignificanceLow-dose amitriptyline (AM) is an off-label treatment for insomnia and may be an effective and safe alternative to cognitive behavioral therapy for insomnia (CBT-I) in patients with insomnia and medical comorbidity. This randomized controlled non-inferiority trial demonstrated that AM is non-inferior to CBT-I in improving insomnia after 12 weeks, when considering a liberal non-inferiority margin. However, more patients showed clinically relevant improvements with CBT-I. Furthermore, AM was associated with more side effects than CBT-I and its benefits for sleep seem temporary. Therefore, CBT-I should remain the first-line treatment given its broader benefits. If patients insist on medication, AM could be considered. Then patients should be well-informed about potential side effects of AM and the likely temporary effectiveness. Our findings need replication.

Patients with psychophysiological insomnia (PI) experience hyperarousal, especially as a reaction to sound stimuli. In the current study, we explored brain activity changes in response to sleep-related sounds (SS) in patients with insomnia after cognitive behavioral therapy for insomnia (CBT-I). In 14 drug-free PI patients, regional brain activity in response to SS, and to white noise sound (NS) as neutral stimuli, was investigated before and after individual CBT-I using functional magnetic resonance imaging. Blood oxygen level-dependent (BOLD) signals to SS and NS were compared before and after CBT-I. In addition, the association between clinical improvement after CBT-I and changes in brain activity in response to SS and NS was analyzed. Compared with baseline, regional brain activity in response to SS after CBT-I decreased in the left middle temporal and left middle occipital gyrus. In regression analysis, a reduction in the Dysfunctional Beliefs and Attitudes about Sleep (DBAS) Scale score after CBT-I was associated with decrease in brain activity in response to SS in both thalami. However, brain activity in response to NS showed no BOLD signal changes and no association with DBAS change. Cortical hyperactivity, which may cause hyperarousal in PI, was found to decrease after CBT-I. CBT-I targeting changes in beliefs and attitudes about sleep may induce its therapeutic effects by reducing thalamic brain activity in response to sleep-related stimuli.