The effect of continuous positive airway pressure usage on sleepiness in obstructive sleep apnoea: real effects or expectation of benefit?
- Megan R Crawford1,2,
- Delwyn J Bartlett1,
- Steven R Coughlin3,4,
- Craig L Phillips1,5,
- Alister M Neill6,
- Colin A Espie1,2,
- George C Dungan II1,
- John P H Wilding3,4,
- Peter M A Calverley3,4,
- Ronald R Grunstein1,7,
- Nathaniel S Marshall1
- 1NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, Sydney Medical School, University of Sydney, Sydney, Australia
- 2University of Glasgow Sleep Centre, University of Glasgow, Glasgow, UK
- 3Department of Obesity and Endocrinology, Clinical Sciences Centre, University of Liverpool, Liverpool, UK
- 4Department of Respiratory Medicine, Clinical Sciences Centre, University of Liverpool, Liverpool, UK
- 5Department of Respiratory and Sleep Medicine, Royal North Shore Hospital Sydney, Australia
- 6WellSleep, Department of Medicine, University of Otago at Wellington, Wellington, New Zealand
- 7Department of Respiratory and Sleep Medicine, Royal Prince Alfred Hospital, Sydney, Australia
- Correspondence to Dr Nathaniel S Marshall, Sydney Nursing School, University of Sydney, Blg MO2, University of Sydney, Sydney, NSW 2006, Australia;
Contributors MRC: conception and design, acquisition of data, analysis and interpretation of data and drafting and final approval of article. DJB, JPHW and PC: acquisition of data, revision and final approval of article. SRC, CLP, AN and RRG: acquisition of data, revision of article, final approval of article. CAE and GD: revision and final approval of article. NSM: conception and design, acquisition of data, analysis and interpretation of data, drafting and revising article and final approval of article.
- Received 11 January 2012
- Accepted 23 April 2012
- Published Online First 26 May 2012
Rationale 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.
Objectives 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.
Measurements and main 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.
- placebo effects
- respiratory measurement
- sleep apnoea
- clinical epidemiology
- oxidative stress
- assisted ventilation
- rare lung diseases
- non-invasive ventilation
- COPD exacerbations
- ambulatory oxygen therapy
- COPD pharmacology
- long term oxygen therapy
- lung physiology
- respiratory muscles
- short burst oxygen therapy
A version of this study has been presented in poster format at the 20th Congress of the European Sleep Research Society, Lisbon, Portugal, September 2010, at the Australasian Sleep Association meeting in Christchurch, New Zealand, October 2010 and at the World Sleep Federation meeting in Kyoto, Japan, October 2011.
Funding The Health Research Council of New Zealand (grant 00/285); The National Health and Medical Research Council of Australia (grants 202916; 301936; 457355; 571179; 571421 and 512498); British Heart Foundation (grant 2001).
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.