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Cognitive Behavioral Therapy for Insomnia in People With Chronic Disease: A Systematic Review and Meta-Analysis

Author/s: 
Amelia J. Scott, Ashleigh B. Correa, Madelyne A. Bisby

Importance: Insomnia is highly prevalent among individuals with chronic disease (eg, chronic pain, cardiovascular disease, and cancer) and results in poorer disease outcomes and quality of life. Cognitive behavioral therapy for insomnia (CBT-I) is recommended as first-line treatment for insomnia. However, concerns remain about its applicability and efficacy in people with chronic disease.

Objective: To evaluate the nature, efficacy, and acceptability of CBT-I in adults with chronic disease, and to identify moderators of treatment outcomes.

Data sources: Systematic searches were conducted in PsycINFO, Medline, Embase, and CENTRAL from database inception to June 5, 2025. Additional records were identified from reference lists of relevant reviews and studies.

Study selection: Eligible studies were randomized clinical trials (RCTs) involving adults (aged ≥18 years) with chronic disease and insomnia. Studies using CBT-I with measured sleep outcomes were included.

Data extraction and synthesis: Two assessors extracted data from RCTs. Hedges g was used to calculate effect sizes, and random effects meta-analyses were conducted. Heterogeneity was assessed via I2. Subgroup analyses examined whether outcomes varied by delivery format, chronic condition type, or control group.

Main outcomes and measures: Primary outcomes included insomnia severity, sleep efficiency, and sleep onset latency. Secondary outcomes included treatment acceptability and adverse effects.

Results: Sixty-seven RCTs (5232 participants) met inclusion criteria, including chronic diseases such as cancer, chronic pain, irritable bowel syndrome, and stroke. CBT-I was associated with significantly improved outcomes for insomnia severity (g = 0.98; 95% CI, 0.81-1.16) and moderate effect sizes regarding sleep efficiency (g = 0.77; 95% CI, 0.63-0.91) and sleep onset latency (g = 0.64; 95% CI, 0.50-0.78). Subgroup analyses revealed some sample, treatment, and methodological moderators (eg, longer treatment yielded better outcomes for sleep efficiency and sleep onset latency). Satisfaction with CBT-I was high, with a mean dropout rate of 13.3%. Treatment-related adverse effects were rare.

Conclusions and relevance: This systematic review and meta-analysis showed that CBT-I demonstrated strong efficacy and acceptability in chronic disease populations, with moderate to large effect sizes that appear comparable to those in non-chronic disease populations. Efficacy of CBT-I was similar across a range of disease subgroups. Future research should explore the role and nature of treatment adaptations for specific populations and increase access to CBT-I in medical settings.

Keywords 
sleep medicine Geriatrics psychotherapy neurology

Efficacy and Safety of Seltorexant in Insomnia Disorder: A Randomized Clinical Trial

Author/s: 
Sofie Mesens, Andrew D Krystal, Rama Melkote, Haiyan Xu, Gahan Pandina, Jay B Saoud, Remy Luthringer, Adam Savitz, Wayne C Drevets

Importance: Existing pharmacological treatments for insomnia have significant limitations.

Objective: To assess the effective dose range, safety, and tolerability of the novel selective orexin-2 receptor antagonist seltorexant in insomnia disorder.

Design, setting, and participants: This randomized, double-blind, active- and placebo-controlled, dose-finding, polysomnography study was conducted from November 2017 to April 2019 at 55 sites in 6 countries and analyzed in August 2019. The timeline for submission of this data for publication was impacted by internal strategic decision-making. Adults (aged 18-64 years) and older adults (aged 65-85 years) with insomnia (Insomnia Severity Index score ≥15) and no psychiatric comorbidity were included.

Interventions: Participants were randomized 1:1:1:1:1 to receive nightly oral-seltorexant (5 mg, 10 mg, or 20 mg), placebo, or zolpidem (5-10 mg) for 14 days.

Main outcomes and measures: Primary and key secondary outcomes included the dose-response relationship of night 1 latency to persistent sleep (LPS) and wake after sleep onset over the first 6 hours (WASO-6). Other secondary outcomes included night 13 LPS and WASO-6. Due to asymmetrical distributions of LPS and WASO-6 at baseline, log transformation was applied and results were expressed as back-transformed least-squares mean (LSM) ratios for comparisons between groups.

Results: Overall, 364 participants (mean [SD] age, 57.8 [12.4] years; 246 [67.6%] female) received seltorexant, 5 mg (n = 71), 10 mg (n = 74), or 20 mg (n = 71); placebo (n = 75); or zolpidem (n = 73). The night 1 dose-response relationship for LPS was significant (with trend test t statistics ≥3.99 and adjusted P values <.001 for all 4 prespecified models), with greater improvements in seltorexant, 10 mg and 20 mg, vs placebo (10 mg: LSM ratio, 0.64; 90% CI, 0.51-0.81; 20 mg: LSM ratio, 0.51; 90% CI, 0.41-0.64) and in seltorexant, 20 mg, vs zolpidem (LSM ratio, 0.71; 90% CI, 0.57-0.88). The night 1 dose-response relationship for WASO-6 was also significant, with trend test t statistics ≥3.99 and adjusted P values <.001 for all 4 prespecified models (seltorexant, 10 mg: LSM ratio, 0.68; 90% CI, 0.55-0.85; seltorexant, 20 mg: LSM ratio, 0.60; 90% CI, 0.48-0.74). Night 1 LPS and WASO-6 improvements were maintained on night 13 for seltorexant, 10 mg and 20 mg, but diminished for zolpidem. On night 13, compared with zolpidem, seltorexant, 10 mg and 20 mg, improved LPS by 30% and 28%, respectively, and seltorexant, 20 mg, improved WASO-6 by 31%. Treatment-emergent adverse events (TEAEs) were lower across the combined seltorexant doses (73/216 [33.8%]) relative to placebo (37/75 [49.3%]) and zolpidem (31/73 [42.5%]). Two participants experienced serious TEAEs during the double-blind phase (1 in the seltorexant, 20 mg, group and 1 in the zolpidem group). Three participants in the seltorexant, 5 mg, and 1 in the seltorexant, 20 mg, group experienced asymptomatic electrocardiogram-related TEAEs leading to discontinuation.

Conclusions and relevance: Among participants with insomnia in this study, seltorexant, 10 mg and 20 mg, improved sleep initiation and maintenance throughout 14 days of treatment. Seltorexant was generally well tolerated.

Trial registration: ClinicalTrials.gov Identifier: NCT03375203.

Keywords 
sleep medicine neurology Psychiatry and Behavioral Health Seltorexant Insomnia medications sleep disorders
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