Effect of Suvorexant vs Placebo on Total Daytime Sleep Hours in Shift Workers: A Randomized Clinical Trial

Abstract

Importance: Many shift workers have difficulty sleeping during the daytime owing to an inappropriately timed circadian drive for wakefulness.

Objective: To determine whether a dual hypocretin receptor antagonist would enable shift workers to have more daytime sleep.

Design, setting, and participants: This double-blind, placebo-controlled randomized clinical trial included 2 weeks of baseline data and 3 weeks of intervention data, from March 2016 to December 2018. Individuals were recruited through poster advertisements in the broader San Francisco Bay area in California. From an initial voluntary recruitment cohort of 38 shift workers, 19 individuals with self-reported difficulty sleeping during the daytime following night work shift were included. Data were analyzed from Janaury to March 2019.

Interventions: 1 week of 10 mg suvorexant or placebo, titrated upward to 20 mg suvorexant or placebo for 2 additional weeks.

Main outcomes and measures: Objective (ie, actigraphy) and subjective (ie, sleep logs) measures of sleep.

Results: Among 19 participants who completed the study (mean [SD] age, 37.7 [11.1] years; 13 [68%] men), 8 participants (42%) were assigned to the suvorexant group and 11 participants (58%) were assigned to the placebo group. Compared with individuals in the placebo group, individuals in the suvorexant group increased their objective total sleep time by a mean (SE) of 1.04 (0.53) hours (P = .05) at the end of 1 week of 10-mg doses and by 2.16 (0.75) hours (P = .004) by the end of the 2 weeks of 20-mg doses. Subjective sleep was similarly improved as, compared with the placebo group, individuals in the suvorexant group increased their subjective total sleep time by a mean (SE) of 2.08 (0.47) hours (P < .001) at the end of 1 week of 10-mg doses and by 2.97 (0.56) hours (P < .001) by the end of the 2 weeks of 20-mg doses. Physician ratings of daytime sleep aligned with these measures, as there was no change in the placebo group and a much improved change in the suvorexant group. No adverse events were reported in the suvorexant group.

Conclusions and relevance: This pilot study found that the use of a dual hypocretin receptor antagonist in shift workers under real-world conditions resulted in more than 2 extra hours of daytime sleep per episode. Future research should confirm this pilot finding in a larger sample size and examine whether, over the long term, use of this medication has a concomitant improvement in medical and psychiatric health as well as workplace performance and safety.

Trial registration: ClinicalTrials.gov Identifier: NCT02491788.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Zeitzer reported receiving personal fees from Lumos Health outside the submitted work. Dr McBean reported receiving personal fees from Jazz Pharmaceuticals outside the submitted work. No other disclosures were reported.

Figures

Figure 1.. Diagram of Participant Flow Through Trial

aOne participant in the suvorexant and 1 participant in the placebo treatment groups were excluded from actigraphy-based sleep analyses owing to data loss.

Figure 2.. Change in Sleep Characteristics From Baseline to Phase 1 (10 mg) to Phase 2 (20 mg)

aStatistically significantly difference vs baseline. bStatistically significantly difference vs placebo. cStatistically significantly difference vs phase 1 (10 mg). Data on subjective total sleep time (TST) (A), sleep onset latency (C), and subjective sleep quality (SSQ) (D) were derived from patient-reported sleep logs; objective TST (B), from actigraphy. Participants receiving placebo are shown as open boxes; those receiving suvorexant are shown as closed circles. Points indicate mean, and whiskers, SD.

Figure 3.. Change in Clinical Global Impressions Improvement (CGII) Scores Among Participants

aStatistically significant difference in placebo vs suvorexant and vs baseline is noted. Individual participants and their trajectories are shown as dots; group medians, horizontal black bars.