Trial reportJournal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine2023
The norepinephrine reuptake inhibitor reboxetine alone reduces obstructive sleep apnea severity: a double-blind, placebo-controlled, randomized crossover trial.
Trial report in Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 3 of them syntheses that pooled it.
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
19 citing papers in PubMed, 3 syntheses or guidelines pooled it, 27 citations in OpenAlex.
- Are noradrenergics combined with antimuscarinics the future pharmacologic treatment for obstructive sleep apnea? A systematic review and meta-analysis of randomized controlled trials.Sleep & breathing = Schlaf & Atmung · 2024Pooled it
- Effect of norepinephrine reuptake inhibitors combined with antimuscarinic agents vs monotherapy for OSA: a systematic review and meta-analysis.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2024Pooled it
- Pharmacological treatment for obstructive sleep apnea: A systematic review and meta-analysis.Clinics (Sao Paulo, Brazil) · 2024Pooled it
- Effect of viloxazine and trazodone in obstructive sleep apnoea: a randomised, placebo-controlled, cross-over study.Thorax · 2025Trial
- Effects of the Combination of Pimavanserin and Atomoxetine on OSA Severity: A Randomized Crossover Trial.Chest · 2025Trial
- The Combination of Aroxybutynin and Atomoxetine in the Treatment of Obstructive Sleep Apnea (MARIPOSA): A Randomized Controlled Trial.American journal of respiratory and critical care medicine · 2023Trial
- Pharmacotherapy in obstructive sleep apnoea: a clinical guide.Sleep & breathing = Schlaf & Atmung · 2026Review
- Review
- Review
- Research Priorities for Translating Endophenotyping of Adult Obstructive Sleep Apnea to the Clinic: An Official American Thoracic Society Research Statement.American journal of respiratory and critical care medicine · 2025Article
- Sleep Disorders and Stroke: Pathophysiological Links, Clinical Implications, and Management Strategies.Medical sciences (Basel, Switzerland) · 2025Review
- [Can drug therapy for obstructive sleep apnea be expected after all?]Innere Medizin (Heidelberg, Germany) · 2025Review
- Images: Combined positive air way pressure and atomoxetine-oxybutynin for the treatment of severe obstructive sleep apnea.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2025Article
- Understanding the clinical management of co-occurring sleep-related bruxism and obstructive sleep apnea in adults: A narrative and critical review.Journal of prosthodontics : official journal of the American College of Prosthodontists · 2025Review
- Noradrenergic therapies in neurodegenerative disease: from symptomatic to disease modifying therapy?Brain communications · 2025Review
- Case-control study of heart rate variability and sleep apnea in childhood sickle cell disease.Journal of sleep research · 2024Article
- The Complex Relationship between Neuromodulators, Circadian Rhythms, and Insomnia in Patients with Obstructive Sleep Apnea.International journal of molecular sciences · 2024Article
- Article
- Development of a combination of noradrenergic and antimuscarinic drugs for the treatment of obstructive sleep apnea: Challenges and progress.Frontiers in sleep · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
STUDY
objectivesRecent findings indicate that noradrenergic and muscarinic processes are crucial for pharyngeal muscle control during sleep. However, to date, reductions in obstructive sleep apnea (OSA) severity have only been detected when noradrenergic agents are combined with an antimuscarinic. Accordingly, this study aimed to determine if reboxetine alone and combined with oxybutynin reduces OSA severity. The pathophysiological mechanisms underpinning the effects of these agents were also investigated via endotyping analysis.
methodsSixteen people (6 women) with OSA completed 3 polysomnograms (∼1-week washout) according to a double-blind, placebo-controlled, three-way crossover design across 2 sites. Single doses of 4 mg reboxetine, placebo, or 4 mg reboxetine + 5 mg oxybutynin were administered before sleep (order randomized).
resultsReboxetine reduced the apnea-hypopnea index (primary outcome) by 5.4 (95% confidence interval -10.4 to -0.3) events/h,
conclusionsThese findings show the first evidence that reboxetine alone reduces OSA severity. The data provide novel insight into the role of norepinephrine reuptake inhibitors on upper airway stability during sleep and are important to inform future pharmacotherapy development for OSA. CLINICAL
trial registrationRegistry: Australian New Zealand Clinical Trials Registry; Name: Reboxetine and Combination Therapy with AD128 in Sleep Apnoea Trial: A Double-Blind, 3-Way Cross-Over Study; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374614&isReview=true; Identifier: ACTRN12620000662965. CITATION: Altree TJ, Aishah A, Loffler KA, Grunstein RR, Eckert DJ. The norepinephrine reuptake inhibitor reboxetine alone reduces obstructive sleep apnea severity: a double-blind, placebo-controlled, randomized crossover trial.
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What Socratic 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 Socratic graph.