Placebo response in objective and subjective measures of hypersomnia in randomized clinical trials on obstructive sleep apnea. A systematic review and meta-analysis.

Sleepiness is one of the outcomes most used in randomized clinical trials (RCT) on the effect of treatments for obstructive sleep apnea (OSA). Furthermore, it is known that there is a placebo effect, especially in subjective measures. Therefore, given that sleepiness is a subjective measure, the objective of this systematic review with meta-analysis and three-level meta-regression was to assess the response to different placebos (pills and sham-CPAP) used in RCTs in OSA, both on subjective (Epworth Sleepiness Scale [ESS]) and objective (Multiple Sleep Latency Test [MSLT], Maintenance Wake Test [MWT], the Osler test and the Psychomotor Vigilance Task [PVT]). We observed a statistically significant placebo effect in both subjective and objective measures of hypersomnia, and in both sham-CPAP and pills. This placebo effect was greater, even clinically significant, in subjective measures (ESS: -2.84 points) and in those RCTs that used pills as a placebo. In the meta-regression, only a higher baseline value of the ESS and Osler test was related to the placebo effect.