Objective: To examine the efficacy of tasimelteon for the treatment of non-24-hour sleep-wake disorder using evidence from controlled clinical trials.

Data sources: Citations in Google Scholar and PubMed from January 1, 2008, to May 31, 2014, were identified using tasimelteon as the search term.

Study selection and data extraction: Results were limited to human trials published in English. Trials that compared tasimelteon with placebo were included.

Data synthesis: A phase II trial (n = 39) evaluated the effects of tasimelteon versus placebo on improvements in sleep efficiency and the ability to shift circadian rhythms over 3 days. Significant shifts in circadian rhythm were only observed for 100-mg tasimelteon. A phase III trial (n = 412) evaluated the effects of tasimelteon versus placebo on assessment of latency to persistent sleep and wake after sleep onset; significant advantages were observed in tasimelteon recipients. The SET (Safety and Efficacy of Tasimelteon) trial (n = 84) enrolled blind men and women with Non-24. They received placebo or tasimelteon 20 mg daily. Tasimelteon recipients had significantly (P = 0.0025) better entrainment and N24CRS scores. The RESET (Randomized Withdrawal Study of the Efficacy and Safety of Tasimelteon) trial (n = 20) enrolled entrained participants from the SET trial who received 20 mg of tasimelteon or placebo daily for 8 weeks. The primary objective was to evaluate the maintenance of effect of tasimelteon to entrain circadian rhythms. Tasimelteon was associated with significantly (P = 0.0055) greater entrainment than placebo.

Conclusion: Tasimelteon improves sleep initiation and maintenance in patients with Non-24 who have a shift in endogenous circadian rhythms. However, the cost of this agent limits its use.