Suvorexant Tablets (Belsomra ®)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
The first in a new class of orexin receptor antagonists has been approved by the FDA for the treatment of insomnia. Orexins are hypothalamic neuropeptides that appear to have a role in maintaining wakefulness.1 Suvorexant is marketed by Merck & Co. as Belsomra.
Suvorexant is indicated for the treatment of insomnia (i.e., difficulty falling asleep and/or staying asleep).1
The recommended dose is 10 mg once nightly within 30 minutes of going to bed.1 There should be at least 7 hours before planned awakening. If the 10 mg dose is tolerated but not effective, the dose may be increased to 20 mg nightly. Patients taking a moderate CYP3A inhibitor should start with a 5 mg dose and may increase to a 10 mg dose. Suvorexant should be avoided in patients taking a strong CYP3A inhibitor. The onset of effect may be delayed if taken with or after a meal.
Suvorexant is available as 5 mg, 10 mg, 15 mg, and 20 mg tablets.
There has been no evidence of physical dependence with prolonged use or withdrawal symptoms after discontinuation.1 The drug appears to be safe and well tolerated over 1 year with nightly use.2
Suvorexant at doses of 40 mg, 80 mg, and 150 mg had similar abuse liability in recreational poly drug users as zolpidem.1 It carries the same class warning for abnormal thinking, behavioral changes, and worsening of depression/suicidal ideation as other hypnotics.1 Sleep paralysis, hypnagogic/hypnopompic hallucinations, and cataplexy-like symptoms can occur with suvorexant.1
Suvorexant is a highly selective antagonist of orexin receptors OX1R and OX2R. Orexin are hypothalamic neuropeptides that are important in regulating wakefulness.3 The drug’s efficacy and safety were evaluated primarily in two 3-month, randomized, placebo-controlled, clinical trials in subjects with insomnia characterized by difficulties falling asleep and staying asleep.1 In two studies with similar design, subjects were randomized 2:1 to suvorexant (20 mg if ages 18-64 or 15 mg if age ≥ 65 years) or placebo.1 Sleep latency and sleep maintenance were assessed by polysomnography and patient estimation. In study 1 (n = 483), sleep latency was reduced by 34 minutes (baseline 69 minutes) compared to -23 minutes for placebo (baseline 66 minutes), a statistically significant difference of 10 minutes at 1 month. The effect was less at 3 months, -35 vs -27 (difference of 8 minutes). In the second study (n = 431), the drug was less effective, with a difference of 8 minutes at 1 month and no difference at 3 months. In terms of patient-estimated time-to-sleep onset, the difference ranged from 5-8 minutes over the course of the study. Polysomnographic assessment of sleep maintenance showed a reduction of 24-26 minutes in time awake after sleep onset at 1 month (mean baseline, approximately 118 minutes) and 17-31 minutes at 3 months. Patient-estimated total sleep time changes were 16-21 minutes at 1 month and 11-22 minutes at 3 months (baseline of approximately 310 minutes). No clear rebound effects were observed after nightly dose for 3 months. Some patients may experience impaired driving performance the next day, particularly at the 20 mg dose.1 Also, next-day effect on memory or balance may be experienced by some. Suvorexant did not appear to have any respiratory depressant effect in healthy subjects and those with mild-to-moderate chronic obstructive pulmonary disease.1 The drug seems well tolerated, with somnolence as the most common side effect (7% vs 3% for placebo).
Suvorexant is the first in a new class of drugs for the treatment of insomnia. It has been suggested that it may be safer (i.e., greater therapeutic margin for sleep vs cognitive disturbance in animals) than the nonbenzodiazepine hypnotics (Z-drugs) such as zolpidem and eszopiclone.4 There are currently no published comparative trials; however, numerical results reported for suvorexant seem modest compared to those reported for the Z-drugs. For example, suvorexant decreased sleep latency by 5-10 minutes compared to about 22 minutes reported for the Z-drugs.5,6 How suvorexant differs from eszopiclone or zolpidem in terms of sleep quality and sleep depth is not known. The ultimate role of suvorexant in the treatment of insomnia remains to be determined. The cost was not available at the time of this review.1 Suvorexant is a Schedule IV controlled substance.
- Belsomra Prescribing Information. Whitehouse Station, NJ: Merck & Co. Inc.; August 2014.
- Michelson D, et al. Safety and efficacy of suvorexant during 1-year treatment of insomnia with subsequent abrupt treatment discontinuation. Lancet Neurol 2014;13:461-471.
- Mieda M, Sakurai T. Orexin (hypocretin) receptor agonists and antagonists for treatment of sleep disorders. Rationale for development and current status. CNS Drugs 2013;27:83-90.
- Uslaner JM, et al. Orexin receptor antagonists differ from standard sleep drugs by promoting sleep at doses that do not disrupt cognition. Sci Transl Med 2013;5:179ra44.
- Erman MK, et al. A polysomnographic placebo-controlled evaluation of the efficacy and safety of eszopiclone relative to placebo and zolpidem in the treatment of primary insomnia. J Clin Sleep Med 2008;4:229-234.
- Huedo-Medina TB, et al. Effectiveness of non-benzodiazepine hypnotics in treatment of adult insomnia: Meta-analysis of data submitted to the Food and Drug Administration. BMJ 2012;345;e8343.