Date of Award


Degree Type

Selective Evidence-Based Medicine Review

Degree Name

Master of Science in Health Sciences - Physician Assistant


Physician Assistant Studies

Department Chair

John Cavenagh, MBA, PhD, PA-C


OBJECTIVE: The objective of this systematic review is to determine whether or not “Are inverse agonists of the Histamine H3 receptor effective in reducing excessive daytime sleepiness (EDS) in individuals with sleep disorders?”

DESIGN: Review of two randomized controlled trials and one cross-sequential pilot study. All studies were primary sources, published in the English language and from 2008-2017.

DATA SOURCES: A single-blind, placebo controlled, cross-sequential study comparing an H3 inverse agonist to placebo in narcoleptics. Two randomized, double-blind, placebo controlled studies; one in narcoleptic patients and one in obstructive sleep apnea (OSA) patients. All studies found using PubMed and Cochrane databases.

OUTCOMES MEASURED: All three trials assessed the efficacy of using an H3 inverse agonist to reduce EDS symptoms in patients with either narcolepsy or obstructive sleep apnea. EDS severity was assessed using the Epworth Sleepiness Scale (ESS), an eight question selfadministered questionnaire that assess an individual’s likelihood of falling asleep in normal everyday settings. Scores range 0-24, with a higher score correlating with more severe EDS.

RESULTS: The pilot study done by Lin J-S et al. showed a significant reduction in ESS score of 4.86 (p =0.0006). The RCT done by Dauvilliers (2013) concluded with a significant ESS score reduction of -3.0 (p= 0.024) when compared to placebo. The final study involving OSA patients done by Herring et al. showed a larger reduction in ESS scores when treated with an H3 inverse agonist compared to treatment with a placebo. These results were not proven to be statistically significant.

CONCLUSIONS: These results suggest that H3 inverse agonists are effective at reducing EDS symptoms in patients with sleep disorders. All three studies provided evidence of reduced ESS scores, indicating a perceived improvement in EDS symptoms with the use of an H3 inverse agonist. Two of the three studies provided statistically significant reductions ESS scores when compared to placebo.