Evidence mapPaperPMID 36004739Full record

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.

Thomas J Altree, Atqiya Aishah, Kelly A Loffler, Ronald R Grunstein, Danny J Eckert

Open access · greenAbstract readRandomized Controlled Trial
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 3 pooled it
2.9field-weighted citation impact, top 8% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

19 citing papers in PubMed, 3 syntheses or guidelines pooled it, 27 citations in OpenAlex.

  1. Pooled it
  2. 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 · 2024
    Pooled it
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  7. Pharmacotherapy in obstructive sleep apnoea: a clinical guide.Sleep & breathing = Schlaf & Atmung · 2026
    Review
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  13. 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 · 2025
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 4 institutions in 1 country.

Thomas J AltreeFlinders Health and Medical Research Institute/Adelaide Institute for Sleep Health, Flinders University, Bedford Park, South Australia, Australia.
Atqiya AishahFlinders Health and Medical Research Institute/Adelaide Institute for Sleep Health, Flinders University, Bedford Park, South Australia, Australia.
Kelly A LofflerFlinders Health and Medical Research Institute/Adelaide Institute for Sleep Health, Flinders University, Bedford Park, South Australia, Australia.
Ronald R GrunsteinCentre for Sleep and Chronobiology, The Woolcock Institute of Medical Research, The University of Sydney and Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.
Danny J EckertFlinders Health and Medical Research Institute/Adelaide Institute for Sleep Health, Flinders University, Bedford Park, South Australia, Australia.
Adelaide Institute for Sleep Health · AUFlinders University · AUUNSW Sydney · AUWoolcock Institute of Medical Research · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

Sleep Apnea, ObstructiveAustraliaCross-Over StudiesDouble-Blind MethodFemaleHumansMaleMandelic AcidsReboxetineMandelic AcidsoxybutyninReboxetinepharmacotherapyprecision medicinerespiratorysleep-disordered breathingupper airway physiology

Identifiers

PMID36004739
PMCPMC9806793
OpenAlexW4293104971

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.