SEARCH METHODS: We searched the following databases on 4 February 2021: Cochrane Register of Studies (CRS Web), MEDLINE (Ovid, 1946 to 1 February 2021), and reference lists of articles. CRS Web includes randomized or quasi-randomized controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialized registers of Cochrane Review Groups, including the Cochrane
Epilepsy Group. We previously searched the WHO ICTRP separately when loading of ICTRP records into CRS Web was temporarily suspended.
SELECTION CRITERIA: Randomized studies comparing any medication to placebo, another medication, or a behavioral intervention.
DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data and assessed trial quality. We contacted study authors for additional data. We collected data on adverse events from the included trials.
MAIN RESULTS: We included three trials, with a total of 112 participants. Risk of bias was low for the included studies. Two
pharmaceutical company-sponsored trials compared
modafinil with placebo, involving 102 participants, nearly all of whom had
idiopathic hypersomnia without long sleep time.
Modafinil significantly improved self-reported
sleepiness on the Epworth
Sleepiness Scale by 5.08 points more than placebo (95% confidence interval (CI) 3.01 to 7.16; 2 studies, 101 participants; high-certainty evidence).
Modafinil also significantly improved disease severity on the Clinical Global Impression of Severity scale by 1.02 points (95% CI 0.11 to 1.93; 1 study, 30 participants; moderate-certainty evidence) and resulted in a greater proportion of participants who were "much improved" or "very much improved" on the Clinical Global Impression of Change (odds ratio (OR) for improvement 5.14, 95% CI 1.76 to 15.00; 1 study, 70 participants; moderate-certainty evidence). Ability to remain awake on the Maintenance of Wakefulness Test was significantly improved with
modafinil, by 4.74 minutes more than with placebo (95% CI 2.46 to 7.01; 2 studies, 99 participants; high-certainty evidence). Ratings of exhaustion and effectiveness/performance were improved with
modafinil compared to placebo in one study. Number of
naps per week was no different between
modafinil and placebo across two studies. Participants receiving modafinil experienced more side effects, although the difference did not reach statistical significance (OR 1.68, 95% CI 0.28 to 9.94; 2 studies, 102 participants; low-certainty evidence). One trial studying 20 participants with different disorders of
sleepiness included 10 participants with
idiopathic hypersomnia, with or without long sleep time, and compared
clarithromycin to placebo. We only included the subset of trial data for those participants with
idiopathic hypersomnia, per our protocol. There were no significant differences between
clarithromycin and placebo for the Epworth
Sleepiness Scale, psychomotor vigilance testing, sleep inertia, other subjective ratings, or side effects.
AUTHORS' CONCLUSIONS: