The effect of continuous positive airway pressure usage on sleepiness in obstructive sleep apnoea: real effects or expectation of benefit?
BACKGROUND
Placebo responses are complex psychobiological phenomena and often involve patient expectation of benefit. With continuous positive airway pressure (CPAP) treatment of obstructive sleep apnoea, greater hours of CPAP use are associated with reduced sleepiness. However, these open-label studies have not controlled for patient expectation of benefit derived from their knowledge of hours of device use.


OBJECTIVE
To investigate the relative effectiveness of the use of real or placebo CPAP on daytime sleepiness.


METHODS
Patient-level meta-analysis combining data on sleepiness measured by the Epworth Sleepiness Scale from three randomised placebo-controlled crossover trials. Mixed model analysis of variance was used to quantify the effects of real versus placebo device treatment, usage, their interaction and regression to the mean.


RESULTS
Duration of real and placebo CPAP use was correlated within patients (r=0.53, p<0.001). High use of real CPAP reduced sleepiness more than high use of placebo (difference 3.0 points; 95% CI 1.7 to 4.3, p<0.001) and more than low use of real CPAP (difference 3.3; 95% CI 1.9 to 4.7, p<0.0001). High use of placebo was superior to low use of placebo (difference 1.5; 95% CI 0.1 to 2.8, p=0.03). Twenty-nine per cent of the effect of high usage of CPAP (4.2 points; 95% CI 3.3 to 5.1) was explained by the expectation of benefit effect associated with high use of placebo (1.2 points ; 95% CI 0.2 to 2.3).


CONCLUSIONS
A clinically significant proportion of the effectiveness of high CPAP use in reducing sleepiness is probably caused by patient expectation of benefit.
NHMRC Centre for Integrated Research and Understanding of Sleep, Woolcock Institute of Medical Research, Sydney Medical School, University of Sydney, Sydney, Australia.
Megan R
MR
Crawford
Delwyn J
DJ
Bartlett
Steven R
SR
Coughlin
Craig L
CL
Phillips
Alister M
AM
Neill
Colin A
CA
Espie
George C
GC
Dungan
John P H
JP
Wilding
Peter M A
PM
Calverley
Ronald R
RR
Grunstein
Nathaniel S
NS
Marshall
D000704:Analysis of Variance; D045422:Continuous Positive Airway Pressure / Q000379:methods*; D018592:Cross-Over Studies; D006970:Disorders of Excessive Somnolence / Q000517:prevention & control*; D005260:Female; D006801:Humans; D008297:Male; D010919:Placebos; D016032:Randomized Controlled Trials as Topic; D020181:Sleep Apnea, Obstructive / Q000628:therapy*
D010919:Placebos