New treatment for chronic insomnia
Chronic insomnia affects 10-30% of women and up until now has been very difficult to treat. It is an important condition as it is associated with an increased risk of depression and anxiety , cardiovascular disease and reduced quality of life . There have essentially been no medication options available which are safe and effective and therefore there has necessarily been a reliance on complementary therapies. Cognitive behavioural therapy (CBTi) is the most effective treatment, with 1 in every 3-4 people trying it achieving remission of their symptoms, and 1 in 2-3 obtaining some benefit . But for people for whom CBTi and other complementary therapies don’t work there have been very little options.
Daridorexant is a new medication which has just been approved for use in the UK. It helps 1 in every 5-9 people after 1 month of use, and 1 in every 6-12 people after 3 months of use . It is therefore less effective than CBTi and therefore it is recommended that CBTi should be tried initially and daridorexant only be used if this is ineffective.
It works in a novel way compared to other traditional medications used for insomnia. It is a dual orexin receptor antagonist, acting on both orexin 1 and orexin 2 receptors and equipotent on both. The orexin neuropeptides (orexin A and orexin B) act on orexin receptors to promote wakefulness. Daridorexant antagonises the activation of orexin receptors by the orexin neuropeptides and consequently decreases the wake drive, allowing sleep to occur, without altering the proportion of sleep stages (as assessed by electroencephalographic recording in rodents or polysomnography in patients with insomnia). The side effects listed by the manufacturer include daytime sleepiness, headache, dizziness, nausea and fatigue, and less commonly hallucinations (6 in every 1,000) and sleep paralysis (3 in every 1,000).
Daridorexant has been tested for up to 12 months continuous use in individuals and there has been no sign of rebound insomnia upon treatment discontinuation. We await longer term data to understand if it is still effective and safe for use beyond 12 months.
Daridorexant undergoes extensive metabolism and is primarily metabolised by an enzyme called CYP3A4. If you are taking medications which inhibit this enzyme moderately e.g. erythromycin, ciprofloxacin, cyclosporine, then you need to be on half the usual dose. If you are taking medications which inhibit this enzyme significantly e.g. itraconazole, clarithromycin, ritonavir, then you shouldn’t take daridorexant There is also genetic variability in the expression of this enzyme which you can be tested for to see if you are more likely to require a lower dosage to avoid side effects.
References
Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention? JAMA. 1989;262(11):1479–1484
Léger D, Morin CM, Uchiyama M, et al. Chronic insomnia, quality-of-life, and utility scores: comparison with good sleepers in a cross-sectional international survey. Sleep Med. 2012;13(1):43–51
Øystein Vedaa*, Håvard Kallestad*, Jan Scott, Otto R F Smith, Ståle Pallesen, Gunnar Morken, Knut Langsrud, Philip Gehrman, Frances P Thorndike, Lee M Ritterband, Allison G Harvey, Tore Stiles, Børge Sivertsen. Effects of digital cognitive behavioural therapy for insomnia on insomnia severity: a large-scale randomised controlled trial. Lancet Digital Health 2020; 2: e397–406.
François-Xavier Chalet, Pierre-Philippe Luyet, Cristina Rabasa, Cédric Vaillant, Paul Saskin, Ajay Ahuja, Leslie Citrome. Daridorexant in patients with insomnia disorder: number needed to treat, number needed to harm & likelihood to be helped or harmed. Sleep, Volume 46, Issue Supplement_1, May 2023, Page A155