Suvorexant for insomnia: a systematic review of the efficacy and safety profile for this newly approved hypnotic - what is the number needed to treat, number needed to harm and likelihood to be helped or harmed?

Int J Clin Pract. 2014 Dec;68(12):1429-41. doi: 10.1111/ijcp.12568. Epub 2014 Sep 18.


Objective: To describe the efficacy and safety of suvorexant for the treatment of insomnia.

Data sources: The pivotal registration trials were accessed by querying and for the search terms 'suvorexant' and 'MK4305'. Briefing documents from the US Food and Drug Administration Peripheral & Central Nervous System Drugs Advisory Committee and product labelling, provided additional information.

Study selection: All available clinical reports of studies were identified.

Data extraction: Descriptions of the principal results and calculation of number needed to treat (NNT) and number needed to harm (NNH) for relevant dichotomous outcomes were extracted from the available study reports and other sources of information.

Data synthesis: Suvorexant (MK4305) is the first orexin receptor antagonist approved for the treatment of insomnia. This approval was based in part on a Phase 3 clinical development programme that included two similarly designed, 3-month, randomised, double-blind, placebo-controlled, parallel-group studies examining suvorexant 40 and 20 mg in non-elderly adults (age < 65 years) and 30 and 15 mg in elderly patients (age ≥ 65 years). Suvorexant was superior to placebo for sleep latency as assessed both objectively by polysomnography and subjectively by patient-estimated sleep latency; suvorexant was also superior to placebo for sleep maintenance, as assessed both objectively by polysomnography and subjectively by patient-estimated total sleep time. NNT vs. placebo for response as measured by a ≥ 6 point improvement on the Insomnia Severity Index at month 3 was 8 (95% CI 6-14) for both the higher and lower dose regimens. The most commonly encountered adverse event (incidence ≥ 5% and at least twice the rate of placebo) as identified in product labelling is somnolence, with NNH values vs. placebo of 13 (95% CI 11-18) for suvorexant 40 and 30 mg, and 28 (95% CI 17-82) for suvorexant 20 and 15 mg. The efficacy and tolerability profile of suvorexant is similar for those < 65 and ≥ 65 years of age. Rebound insomnia and withdrawal effects were not observed when suvorexant was discontinued after 3 months or after 12 months of nightly use. Because of concerns about dose-related, next-day effects, including sedation, the recommended dose range is 10-20 mg.

Conclusions: Suvorexant appears efficacious and relatively tolerable. Its different mechanism of action and potentially different safety and tolerability profile compared with currently available hypnotics represents a new option for the pharmacological treatment of insomnia.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Azepines / adverse effects
  • Azepines / pharmacokinetics*
  • Azepines / therapeutic use
  • Drug Administration Schedule
  • Humans
  • Hypnotics and Sedatives / adverse effects
  • Hypnotics and Sedatives / therapeutic use*
  • Sleep Initiation and Maintenance Disorders / drug therapy*
  • Treatment Outcome
  • Triazoles / adverse effects
  • Triazoles / pharmacokinetics*
  • Triazoles / therapeutic use


  • Azepines
  • Hypnotics and Sedatives
  • Triazoles
  • suvorexant