Evidence map›Paper›PMID 32006590›Full record

Trial reportChest2020

Effects of the Combination of Atomoxetine and Oxybutynin on OSA Endotypic Traits.

Luigi Taranto-Montemurro, Ludovico Messineo, Ali Azarbarzin, Daniel Vena, Lauren B Hess, Nicole A Calianese, David P White, Andrew Wellman, Scott A Sands

Open access · greenAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Chest, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
67citing papers in PubMed, 3 pooled it
8.9field-weighted citation impact, top 1% 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

67 citing papers in PubMed, 3 syntheses or guidelines pooled it, 119 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
  3. Pooled it
  4. Trial
  5. Atomoxetine plus oxybutynin for symptomatic snoring and airflow limitation in individuals without moderate-to-severe obstructive sleep apnea.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2025
    Trial
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  11. The norepinephrine reuptake inhibitor reboxetine alone reduces obstructive sleep apnea severity: a double-blind, placebo-controlled, randomized crossover trial.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2023
    Trial
  12. Trial
  13. Combination of atomoxetine with the novel antimuscarinic aroxybutynin improves mild to moderate OSA.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2022
    Trial
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  18. Pharmacotherapy in obstructive sleep apnoea: a clinical guide.Sleep & breathing = Schlaf & Atmung · 2026
    Review
  19. Review
  20. Article

7 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 4 institutions in 3 countries.

Luigi Taranto-MontemurroDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital & Harvard Medical School, Boston, MA. Electronic address: ltarantomontemurro@bwh.harvard.edu.
Ludovico MessineoDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital & Harvard Medical School, Boston, MA; Respiratory Medicine and Sleep Laboratory, Department of Internal Medicine, Spedali Civili di Brescia, University of Brescia, Brescia, Italy; Adelaide Institute for Sleep Health, Flinders University, Adelaide, SA, Australia.
Ali AzarbarzinDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital & Harvard Medical School, Boston, MA.
Daniel VenaDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital & Harvard Medical School, Boston, MA.
Lauren B HessDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital & Harvard Medical School, Boston, MA.
Nicole A CalianeseDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital & Harvard Medical School, Boston, MA.
David P WhiteDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital & Harvard Medical School, Boston, MA.
Andrew WellmanDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital & Harvard Medical School, Boston, MA.
Scott A SandsDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital & Harvard Medical School, Boston, MA.
Harvard University · USBrigham and Women's Hospital · USCircadian (United States) · USUniversity of Brescia · IT

Funding

HARVARD CLINICAL AND TRANSLATIONAL SCIENCE CENTER (UL1)UL1RR025758 · NCRR · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2008 to 2011
$91.4M
Wakefulness and Forebrain Activation by Orexin NeuronsP01HL095491 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI WELLMAN, DAVID ANDREW · 2010 to 2019
$25.1M
Validation of a Phenotype Model to Predict Response to Alternative OSA TreatmentsR01HL102321 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI WELLMAN, DAVID ANDREW · 2011 to 2025
$7.3M
Determination of the site of pharyngeal collapse in Obstructive Sleep Apnea patients from snoring soundsR01HL128658 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI WELLMAN, DAVID ANDREW · 2016 to 2025
$4.3M
NCRR NIH HHS UL1 RR025758NHLBI NIH HHS P01 HL095491NHLBI NIH HHS R01 HL102321NHLBI NIH HHS R01 HL128658
6 · The paper itself

Abstract

backgroundWe recently showed that administration of the combination of the noradrenergic drug atomoxetine plus the antimuscarinic oxybutynin (ato-oxy) prior to sleep greatly reduced OSA severity, likely by increasing upper airway dilator muscle activity during sleep. In patients with OSA who performed the ato-oxy trial with an esophageal pressure catheter to estimate ventilatory drive, the effect of the drug combination (n = 17) and of the single drugs (n = 6) was measured on the endotypic traits over a 1-night administration and compared vs placebo. This study also tested if specific traits were predictors of complete response to treatment (reduction in apnea-hypopnea index [AHI] > 50% and < 10 events/h).

methodsThe study was a double-blind, randomized, placebo-controlled trial. The arousal threshold, collapsibility (ventilation at eupneic drive [Vpassive]), ventilation at arousal threshold, and loop gain (stability of ventilatory control, LG1), were calculated during spontaneous breathing during sleep. Muscle compensation (upper airway response) was calculated as a function of ventilation at arousal threshold adjusted for Vpassive. Ventilation was expressed as a percentage of the eupneic level of ventilation (%

resultsCompared with placebo, ato-oxy increased Vpassive by 73 [54 to 91]%

findingsAto-oxy markedly improved the measures of upper airway collapsibility, increased breathing stability, and slightly reduced the arousal threshold. Patients with relatively lower AHI and less severe upper airway collapsibility had the best chance for OSA resolution with ato-oxy.

Indexed as

Adrenergic Uptake InhibitorsAtomoxetine HydrochlorideContinuous Positive Airway PressureCross-Over StudiesDouble-Blind MethodDrug Therapy, CombinationFemaleHumansMaleMandelic AcidsMiddle AgedParasympatholyticsPolysomnographySleepSleep Apnea, ObstructiveTreatment OutcomeAdrenergic Uptake InhibitorsAtomoxetine HydrochlorideMandelic AcidsoxybutyninParasympatholyticsnoradrenergic and antimuscarinicOSA pharmacotherapyOSA phenotypes

Identifiers

PMID32006590
PMCPMC7268440
OpenAlexW3004160311

What OpenQuestion 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 OpenQuestion graph.