The National Institute for Health and Care Excellence (NICE) has recommended daridorexant (QUVIVIQ, Idorsia) as a new treatment option for long-term insomnia but underscored the importance of keeping the duration of treatment as brief as possible.
Long-term insomnia — also known as chronic insomnia or insomnia disorder — is defined as dissatisfaction with quantity or quality of sleep for 3 nights or more per week for at least 3 months with an effect on daytime functioning. The condition — thought to affect around 7% of the UK adult population —has both night-time symptoms as well as a negative impact on physical health, daytime functioning, and overall wellbeing. Furthermore, suboptimal management of the condition is associated with decreased workplace productivity, and an increased risk of workplace accidents, falls, and costly workplace errors.
Lisa Artis, deputy CEO of The Sleep Charity UK, said: "While we all may experience short periods of sleeplessness, people living with chronic insomnia are persistently deprived of the restorative sleep they need, which can have a major impact on their overall health and wellbeing."
The standard first treatment for insomnia is sleep hygiene advice plus cognitive behavioural therapy for insomnia (CBTi). However, access to CBTi varies across England, and there are difficulties accessing CBTi, NICE alerted. "Even when CBTi was available, people with insomnia were often not aware of it," the regulator pointed out.
Tackling Overactive Wakefulness
A key component of the wake and sleep signalling process is the orexin system — made up of orexin A and orexin B neuropeptides, and receptors OX1R and OX2R — which helps promote wakefulness.
This system stimulates targeted neurons in the wake system leading to the release of several chemicals — serotonin, histamine, acetylcholine, norepinephrine — to promote wakefulness. Under normal circumstances, orexin levels rise throughout the day as wakefulness is promoted, and then fall at night.
Overactivity of the wake system is an important driver of insomnia. Daridorexant works by selectively blocking only the activation of orexin receptors, thereby decreasing the brain's "overactive wakefulness".
Daridorexant is taken orally once a night, around half an hour before bed. The list price per pack for the 50mg or the 25mg dose is £1.40 per day.
Evidence presented to an appraisal committee showed a reduction in insomnia with daridorexant compared with placebo over a 12-month period, and that the drug was effective in improving symptoms related to long-term insomnia, reducing the total number of minutes that a person was awake after initially falling asleep, and the time it took for the person to fall asleep after going to bed. After 12 months' treatment, daridorexant was not associated with physical signs of dependency, tolerance, or rebound insomnia after its discontinuation.
Daridorexant Recommended as Second Line
In final draft guidance, NICE said that daridorexant would be offered as a second-line treatment option for long-term insomnia, but only if CBTi had been tried but had not worked, or if CBTi was not available or was unsuitable. It is estimated that just over 20,000 people in England could receive the treatment in the next year.
"There is some uncertainty about its longer-term benefit compared with placebo beyond 12 months, and [about] cost-effectiveness modelling assumptions," cautioned NICE. However, it emphasised that "even accounting for this uncertainty", the cost-effectiveness estimates for daridorexant compared with 'no treatment' was within the range it normally considered to be an acceptable use of NHS resources.
Dr David O'Regan, consultant in psychiatry and sleep medicine, said that the decision by the regulator represented a "significant breakthrough" for chronic insomnia patients. "While other treatment options for insomnia are available, these may not be suitable for long-term use, effective for all patients, or specifically licensed for the treatment of chronic insomnia," he explained.
The regulator stressed that the "length of treatment should be as short as possible", and that treatment with the drug should be assessed within 3 months of starting and should be stopped in people whose long-term insomnia had not responded adequately. If treatment was continued, assessment of whether it was still working should be made at regular intervals.
NICE said that as a new medicinal product containing a new active substance, daridorexant was subject to additional monitoring, and it was therefore important to report on the Yellow Card system any suspected adverse events.
Final NICE guidance is due to be published on 18 October, 2023.