daridorexant for treating long-term insomnia

Last edited 10/2023 and last reviewed 11/2023

Daridorexant for treating long-term insomina

Daridorexant is the first dual orexin receptor antagonist approved for the treatment of chronic insomnia in the EU and has been approved for insomnia in the USA (1)

  • daridorexant is an orally administered dual orexin type 1 and type 2 (OX1 and OX2) receptor antagonist (DORA) developed for the treatment of insomnia
    • endogenous ligands orexin A and orexin B (also known as hypocretin-1 and -2) are produced in the hypothalamus and promote wakefulness through interactions with OX1 and OX2 (2)
    • dual orexin receptor antagonists suppress wakefulness and are generally considered to have a favourable safety profile compared with older classes of insomnia drugs, including less risk of tolerance, dependence, abuse and withdrawal effects (1)
      • in clinical trials
        • daridorexant improved objective sleep onset, objective sleep maintenance and self-reported total sleep time, and self-reported daytime functioning at a 50 mg dose (1)
      • daridorexant was generally well tolerated
        • had a low incidence of adverse events such as (1):
            • sleepiness,
            • fatigue,
            • dizziness and falls
          • most of which were similar to that with placebo
      • efficacy and tolerability of daridorexant were sustained for 12 months
      • had a favourable safety profile compared to other classes of insomnia drugs, minimal residual next-morning effects and improvements in daytime functioning, daridorexant is a useful option for the treatment of insomnia disorder (1)
    • daridorexant is extensively metabolized, primarily by CYP3A4 (89%) and mostly excreted via faeces (about 57%) and urine (about 28%), primarily as metabolites (2)

NICE have recommended daridorexant for insomnia in adults with symptoms lasting >=3 nights per week for >=3 months, where daytime functioning is considerably affected, only if cognitive behavioural therapy for insomnia has been tried but not worked, or is not available or unsuitable

  • daridorexant is recommended for treating insomnia in adults with symptoms lasting for 3 nights or more per week for at least 3 months, and whose daytime functioning is considerably affected, only if
    • cognitive behavioural therapy for insomnia (CBTi) has been tried but not worked, or
    • CBTi is not available or is unsuitable.
  • the length of treatment should be as short as possible
    • treatment with daridorexant should be assessed within 3 months of starting and should be stopped in people whose long-term insomnia has not responded adequately
    • if treatment is continued, assess whether it is still working at regular intervals

  • NICE committee stated "...CBTi is the standard first treatment for people with long-term insomnia after sleep hygiene advice is offered...Clinical trial evidence shows that daridorexant improves symptoms of insomnia compared with placebo for 12 months. The effects if it's taken for longer than this are unknown. A condition of the marketing authorisation is that treatment with daridorexant should be reviewed within 3 months and regularly after that..."

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Related pages:

insomnia