Study suggests atomoxetine/oxybutynin combo reduces AHI

[amenite]

Will be interesting to see if this holds up under further scrutiny. Only 20 study participants but encouraging results.

https://www.sciencemag.org/news/2018/09 ... leep-apnea

[ChicagoGranny]

Not so encouraging.

The trial turned up one potentially problematic finding: Although the drug combination reduced patients’ AHIs, their number of subconscious arousals—the subtle awakenings that leave patients exhausted—remained high. ...

Mason, Veasey, and other sleep apnea experts caution, however, that the findings are extremely preliminary. They note that the pilot study, although double-blind and randomized, included just a small number of patients who took the drug combination for just 1 night.

[amenite]

Certainly worth checking back after more study.

...a combination of atomoxetine and oxybutynin, taken as two pills at bedtime, reduced patients’ frequency of airway obstruction—called the apnea-hypopnea index, or AHI—from a median of 28.5 hourly obstructions on placebo to 7.5 on the pills. In the 15 patients with the highest AHIs, the median reduction was 74%—and every patient experienced at least a 50% reduction

“We’ve never had a drug combination, or any sort of a drug, that consistently improved everybody’s AHI. That’s actually unbelievably exciting,” says Sigrid Veasey of the University of Pennsylvania (UPenn), a physician-researcher who studies sleep. It’s “a great first step,” adds Martina Mason, a sleep physician at the Royal Papworth Hospital in Cambridge, U.K., who co-authored a 2013 review of 30 previous, underwhelming drug trials.

...the findings are extremely preliminary. They note that the pilot study, although double-blind and randomized, included just a small number of patients who took the drug combination for just 1 night.

[yrnkrn]

At PubMed, https://www.ncbi.nlm.nih.gov/pubmed/30395486

The Combination of Atomoxetine and Oxybutynin Greatly Reduces Obstructive Sleep Apnea Severity: A Randomized, Placebo-Controlled, Double-Blind Crossover Trial.
Taranto-Montemurro L1, Messineo L2, Sands SA3, Azarbarzin A4, Marques M5, Edwards BA6, Eckert DJ7, White DP5, Wellman A8.
Author information

Abstract

RATIONALE:
There is currently no effective pharmacological treatment for obstructive sleep apnea (OSA). Recent investigations indicate that drugs with noradrenergic and antimuscarinic effects improve genioglossus muscle activity and upper airway patency during sleep.

OBJECTIVES:
We aimed to determine the effects of the combination of a norepinephrine reuptake inhibitor (atomoxetine) and an antimuscarinic (oxybutynin) on OSA severity (apnea-hypopnea index, AHI; primary outcome) and genioglossus responsiveness (secondary outcome) in people with OSA.

METHODS:
20 people completed a randomized, placebo-controlled, double-blind, crossover trial comparing one night of atomoxetine 80mg plus oxybutynin 5mg (ato-oxy) to placebo administered prior to sleep. The AHI and genioglossus muscle responsiveness to negative esophageal pressure swings were measured via in-laboratory polysomnography. In a subgroup of 9 patients the AHI was also measured when the drugs were administered separately.

MEASUREMENTS AND MAIN RESULTS:
The participants' median [interquartile range] age was 53 [46-58] years and body mass index was 34.8 [30.0-40.2] kg/m2. Ato-oxy lowered AHI by 63% [34-86%], from 28.5 [10.9-51.6] events/h to 7.5 [2.4-18.6] events/h (p<0.001). Of the 15/20 patients with OSA on placebo (AHI>10 events/hr), AHI was lowered by 74% [62-88%] (p<0.001) and all 15 patients exhibited a ≥50% reduction. Genioglossus responsiveness increased ~3-fold, from 2.2 [1.1-4.7]%/cmH2O on placebo to 6.3 [3.0 to 18.3]%/cmH2O on ato-oxy (p<0.001). Neither atomoxetine nor oxybutynin reduced the AHI when administered separately.

CONCLUSION:
A combination of noradrenergic and antimuscarinic agents administered orally before bedtime on one night greatly reduced OSA severity. These findings open new possibilities for the pharmacologic treatment of OSA. Clinical trial registration available at www.clinicaltrials.gov, ID NCT02908529.

[ChicagoGranny]

Something doesn't seem right in the conclusion.

Ato-oxy lowered AHI by 63%

on placebo ... AHI was lowered by 74%

The placebo lowered the AHI more than the drug combination. (Yes, I realize AHI is not a complete measure of the severity of sleep apnea.) On the other hand, the genioglossus responsiveness on the drug combination was impressive.

IMO, the study is barely a start. The number of participants was small, the number of nights was only one, the arousals were a problem, and the significant side effects of the drug combination were not studied.

[gocamels]

There has to be missing data in this abstract. Just looking at what's available, my guess would be that the drugs didn't decrease the number of events, but possibly the severity of those events. Impossible to evaluate with incomplete data. And it's all pretty meaningless given the sample size and trial length. What the study apparently accomplished was convincing someone that it was worth the expense of a more thorough trial.

/eta - Looking at the abstract again, this was a crossover trial, meaning every subject took placebo one night and drug one night.

Of the 15/20 patients with OSA on placebo (AHI>10 events/hr), AHI was lowered by 74% [62-88%] (p<0.001) and all 15 patients exhibited a ≥50% reduction.

What the study is saying is that for the patients who had >10 AHI on their placebo night, the drug combo provided a 74% improvement. Makes more sense now. Funny how missing one word changed the interpretation of results.