Trial reportSleep2025
Low-dose amitriptyline versus cognitive behavioral therapy for insomnia in patients with medical comorbidity: results of a randomized controlled multicenter non-inferiority trial.
Trial report in Sleep, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Cyclodextrin Nanosponge-PVA Hybrid Networks as Supramolecular Reservoir Systems for Amitriptyline.ACS omega · 2026Article
- Treatment Preferences in Patients With Insomnia and Medical Comorbidity: Associated Factors and Impact on Treatment-Outcome.Journal of sleep research · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
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 Significance Low-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.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.