TABLE 7 

Summary of studies assessing the effects of suvorexant (SVX) on sleep

StudyAgeDiagnosisDesign + Number of ParticipantsResultsAdverse EventsConclusion
Citrome (2014)18–87Primary insomniaSystematic review of four phase II and phase III RCTs.LS mean difference from placebo in subjective TST at month 1 (minute): 18.4, P < 0.001 for SVX 15 or 20 mg; 22.7, P < 0.001 for SVX 30 or 40 mg. LS mean difference from placebo in SOL by polysomnography at month 1 (minute): −9.1, P < 0.001 for SVX 15 or 20 mg; −11.4, P < 0.001 for SVX 30 or 40 mg.Rebound insomnia and withdrawal effects not observed after treatment discontinuation. Somnolence is the most common AE.SVX is effective at reducing symptoms of insomnia. Higher doses are more effective but may have a higher risk of AEs.
Herring et al. (2012)18–64Primary insomnia by DSM-IV4-wk crossover RCT. SVX 10 vs. 20 vs. 40 vs. 80 mg/day. N = 254.Objectively-measured LPS (minute) at EOS was changed relative to placebo −2.3 [−12.2, 7.5] for 10 mg/day, −22.3 [−32.3, −12.3] for 20 mg/day, −3.8 [−13.8, 6.3] for 40 mg/day, −9.5 [−19.7, 0.7] for 80 mg/day. However, in general, more robust effects were observed for SVX 40 and 80 mg/day on subjective SOL, objective TST, and subjective QOS.10 and 20 mg/day showed similar levels of adverse effects to placebo, while 40 and 80 mg/day had increased adverse effects. One patient receiving SVX 80 mg/day had a mild visual hallucination and discontinued. Most common AEs were somnolence, headache, and dizziness.SVX is effective at reducing symptoms of insomnia. SVX 10 and 20 mg/day are better tolerated then 40 and 80 mg/day.
Herring et al. (2016)nonelderly (18–64) and elderly (≥65)Primary insomnia by DSM-IV-TRTwo 3-mo RCTs in elderly and non-elderly patients. SVX 40/30 mg/day vs. SVX 20/15 mg/day vs. placebo. N = 1021 in first RCT and N = 1019 in second RCT.Subjective SOL (minute) difference between SVX 40/30 mg/day and placebo at month 3: −8.4 [−12.8, −4.0] in trial 1, −13.2 [−19.4, −7.0] in trial 2.The most common AE that was increased for SVX vs. placebo was next-day somnolence.SVX is effective at reducing symptoms of insomnia. SVX 40/30 mg/day was superior to placebo on almost all subjective and polysomnography end points in both trials; SVX 20/15 mg/day was superior to placebo on many subjective measures.
Kishi et al. (2015)NSPrimary insomnia by DSM-IVSystematic review and meta-analysis of four placebo-controlled RCTs. N = 3076.Mean pooled (15 and 40 mg/day) difference between SVX and placebo in subjective TST at month 1 (minute): −20.16 [−25.01, −15.30]. Mean pooled (15 and 40 mg/day) difference between SVX and placebo in subjective TST at month 1 (minute): −7.62 [−11.03, −4.21].Discontinuation due to all-cause, inefficacy, and intolerability did not differ between groups. SVX group had higher incidence of abnormal dreams, somnolence, excessive daytime sleepiness, fatigue, and dry mouth.SVX is effective at reducing symptoms of insomnia.
Michelson et al. (2014)18+Primary insomnia by DSM-IV-TRYearlong RCT with a subsequent 2-mo randomized discontinuation phase in which participants given placebo were switched to SVX and vice versa. SVX 40 mg/day for patients younger than 65, 30 mg/day for patients older than 65, or placebo. N = 781.Change in subjective SOL (minute) at month 12 for SVX was −26.6 [−30.5, −22.7] vs. −17.0 [−22.6, −11.4] for placebo, P = 0.0055. Change in subjective TST (minute) at month 12 was 60.5 [54.0, 66.9] for SVX vs. 33.0 [23.7, 42.2] for placebo, P < 0.0001.Most common AE, somnolence, reported for 13% of patients receiving SVX vs. 3% of those receiving placebo. Fatigue and dry mouth were also increased for SVX vs. placebo groups.SVX is effective at reducing symptoms of insomnia. SVX is probably not associated with rebound insomnia during discontinuation after 1 yr of treatment.
Sun et al. (2013)18–45Healthy young menFour-period crossover RCT followed by a fifth period to assess pharmacokinetics. SVX 10 vs. 50 vs. 100 mg/day N = 22 (completed 19).SVX 50 and 100 mg decreased LPS and WASO and increased SE and TST.All reported adverse events were mild. The most frequently reported adverse events were somnolence (20% in those receiving SVX 100 mg) and headache.SVX is effective at promoting sleep in healthy subjects without known sleep impairments