Lemborexant, an orexin receptor antagonist sedative-hypnotic: Is it useful for insomnia in psychiatric disorders?

Lemborexant, an orexin receptor antagonist similar to suvorexant, has been approved for the treatment of sleep onset and/or maintenance insomnia. Lemborexant is reviewed and compare to suvorexant from a psychiatric perspective.

Rapidly absorbed (peak 1-3 h), lemborexant has a half-life of 17-19 h (suvorexant half-life 12 h). It is metabolized by CYP3A4/5, with no significant effects of age, sex or weight. Trials for insomnia indicate sustained efficacy beyond 6 months. Lemborexant has not been trialled in major psychiatric disorders. Commenced at 5 mg, lemborexant can then be increased to 10 mg, taken at least 7 h before planned awakening. Adverse effects are higher at 10 mg: somnolence occurs in about 10% while headache and nightmares affect 2-5%, approximately similar to 40 mg suvorexant (recommended suvorexant dose 20 mg). Sleep paralysis, hypnagogic/hypnopompic hallucinations, and cataplexy-like symptoms, complex sleep behaviours and emergence of depression/suicidal ideation can occur. Neither tolerance to sedation nor withdrawal effects on discontinuation have been observed. Whether the differences between lemborexant and suvorexant are clinically relevant is unclear. Like suvorexant, lemborexant appears to be effective in longer-term use for insomnia, but until efficacy and safety are adequately investigated in major mental disorders, clinicians need to monitor patient experience closely.