Orexin-blocking sleep tablets, called dual orexin receptor antagonists (DORAs), treat long-term insomnia by turning down the brain's "stay awake" signal. Orexin is a brain chemical that promotes wakefulness. DORAs block both of its receptors. Older sleeping tablets, such as zopiclone, work differently. They act on the brain's GABA receptor system.
Three DORAs exist. Only one, daridorexant (Quviviq), is licensed in Ireland and the UK. Suvorexant (Belsomra) and lemborexant (Dayvigo) are approved in the US. Lemborexant has been under review by the European Medicines Agency (EMA) since July 2026.
Daridorexant is for adults whose insomnia has lasted at least three months and badly affects their days. In the UK, NICE recommends it only after cognitive behavioural therapy for insomnia (CBT-I), or when CBT-I is unavailable or unsuitable. In Ireland, the HSE has not yet decided whether to fund it.
For how DORAs compare with z-drugs, trazodone and prescribed melatonin, see our overview of prescription sleep medications. This page goes deeper on DORAs alone.
The daridorexant product information explains the mechanism. Orexin A and orexin B act on two receptors to promote wakefulness. Daridorexant blocks both receptors equally. This "decreases the wake drive, allowing sleep to occur", without changing the proportion of sleep stages.
That is the opposite of the new orexin drugs for narcolepsy, which switch the receptor on. Narcolepsy, a condition linked to orexin loss, is listed as a reason not to use daridorexant.
In the US, all three are Schedule IV controlled substances.
Two three-month trials randomised 1,854 adults with insomnia disorder. About 39% were aged 65 or over. Sleep was measured in a sleep lab and by morning diaries.
In the first trial (930 people), at three months, compared with placebo:
These are differences from placebo. Placebo groups also improved, so within-group changes look larger.
The 50 mg dose improved all main and secondary measures, including a daytime sleepiness score. The 25 mg dose did not consistently shorten time to fall asleep. The 10 mg dose, tested in the second trial, was not effective.
Better days are the point of treatment. On the trial's daytime sleepiness questionnaire, 50 mg was 1.9 points better than placebo at three months. On 25 mg, the difference was 1.0 point, and its confidence interval reached zero.
People could continue into a nine-month placebo-controlled extension. In total, 331 people took daridorexant for at least 12 months. NICE notes that effects beyond 12 months are unknown.
After three months, the trials switched people to placebo for a week. The product information found no sign of rebound insomnia at the 50 mg dose. It found no withdrawal symptoms suggesting physical dependence.
A 2022 network meta-analysis in The Lancet pooled 154 trials of insomnia medicines. It found that lemborexant was among the drugs more effective than placebo in short-term treatment. It counted daridorexant and suvorexant among licensed drugs that "can be effective" short term, but with poor tolerability or missing long-term data. Zopiclone caused more people to stop treatment because of side effects than daridorexant did.
A 2026 meta-analysis of six trials of DORAs used for at least six months found sustained improvements in self-reported sleep. Side effects were similar to placebo at six months but higher at 12 months.
The daridorexant product information lists:
In a driving-simulator study of healthy adults aged 50 to 79, 50 mg impaired driving the morning after the first dose. No effect was seen after four nights. Zopiclone impaired driving at both points. The product information recommends about 9 hours between taking it and driving.
The licence covers adults with insomnia on at least three nights a week (in NICE's wording), lasting at least three months, with a considerable effect on daytime functioning.
They are not for:
Extra caution is advised for people over 75, those with severe COPD, psychiatric conditions or a history of substance misuse.
Where they sit: the 2023 European Insomnia Guideline recommends CBT-I as the first-line treatment. When CBT-I is not effective enough, medication can be offered. It says orexin receptor antagonists can be used for up to three months, or longer in some cases. Our guide to CBT-I explains what it involves. We also explain why sleep hygiene tips alone rarely fix insomnia.
We searched ClinicalTrials.gov, the EU clinical trials register and ISRCTN on 3 November 2026. We found no DORA trial for people with insomnia with a site in Ireland or the UK. One University of Oxford study is giving single doses of daridorexant to healthy volunteers to study emotion and learning. That is research, not a treatment option.
If you are waiting for specialist sleep help in Ireland, our guide to HSE outpatient waiting lists explains how the lists work.
Long-term insomnia and low mood often go together. If you are having thoughts of suicide or self-harm, contact Samaritans on 116 123 (Ireland and UK). In Ireland you can also text 50808. In an emergency, call 112 or 999.
Trials found no withdrawal symptoms or signs of abuse in people with insomnia. High doses produced "drug liking" similar to zolpidem in recreational drug users. In the US it is a Schedule IV controlled drug.
The main daridorexant insomnia trials compared it with placebo, not zopiclone. In one driving-simulator study, zopiclone impaired driving after one and four nights; daridorexant only after the first night. The Lancet meta-analysis found more people stopped zopiclone because of side effects.
Studies found it did not worsen breathing in obstructive sleep apnoea. But sleep apnoea needs its own diagnosis and treatment. Tell your GP if you snore or stop breathing at night.
The product information lists narcolepsy as a contraindication. Narcolepsy type 1 involves loss of orexin, the signal these tablets block.
No. Its EU licence, which covers Ireland, makes it a prescription-only medicine. In the UK, NICE guidance sets out when it should be prescribed.
This article is general information, not medical advice. Do not start, stop or change a sleeping tablet without your GP, pharmacist or prescriber.
Reviewed by: Proco Team
Last updated: November 2026