Daridorexant: Independent Evidence on Insomnia, Side Effects & Withdrawal

Table of contents

• Evidence summary
• What daridorexant is
• How it works
• What it is prescribed for
• What works and what does not
• Benefits by claim
• Risks and all side effects
• All interactions
• Who should avoid daridorexant
• Dosage and how to take it
• Follow the money: who makes it and who funded the evidence
• Related research
• Frequently asked questions
• Sources and funding notes

Evidence summary

Independent evidence and credibility scorecard

Independence tier: 1 = no money from the product's seller, 4 = funded by the seller. Credibility: A (highest) to D.

What daridorexant is

Daridorexant is a dual orexin receptor antagonist (DORA). It blocks both known receptors for orexin, a brain chemical that promotes wakefulness (EMA). It is sold as Quviviq in 25 mg and 50 mg film-coated tablets. It is the third orexin antagonist placed under US drug control, after suvorexant (Belsomra) in 2014 and lemborexant (Dayvigo) in 2021 (DEA, Federal Register 2026). NICE noted it was the first dual orexin receptor antagonist approved in the UK and Europe for long-term insomnia (NICE 3.41).

• United States: approved by the FDA on 7 January 2022 as a new molecular entity (NDA 214985, sponsor Idorsia) (Drugs@FDA). It is a Schedule IV controlled substance (FDA label 9.1). In August 2026 the DEA proposed moving all three orexin antagonists to Schedule V, the lowest schedule; the comment period closed on 10 September 2026 (Federal Register, 11 Aug 2026). As of this review the proposal was not final.
• European Union: authorised EU-wide on 29 April 2022. The licence holder is Idorsia Pharmaceuticals Deutschland GmbH (Lörrach, Germany) (EMA EPAR, EU SmPC).
• United Kingdom: prescription-only medicine. The Great Britain licence (PLGB 48711/0002) was first authorised on 26 August 2022 (UK SmPC, emc). NICE recommended it for NHS use on 18 October 2023 (NICE TA922). We could not verify whether it is a controlled drug under UK misuse-of-drugs rules from the sources we fetched.
• Generics: none. The FDA drug database lists no approved generic (ANDA) applications for daridorexant (openFDA Drugs@FDA).
• Originator: Idorsia Ltd. Actelion created Idorsia on 16 June 2017, when it spun off its drug discovery operations and early-stage clinical assets as Johnson & Johnson completed its acquisition of Actelion (J&J SEC filing, 2017). Idorsia is headquartered in Allschwil, Switzerland (Kunz et al. funding statement).
• UK list price: £1.40 per day for either strength, or £42 per pack of 30 tablets, according to the company submission (NICE TA922 section 2.3).

How it works

Orexin A and orexin B are signalling molecules made by a small cluster of neurons. They help keep the brain in the waking state. According to the FDA label, daridorexant binds to and blocks the OX1R and OX2R orexin receptors, which "is thought to suppress wake drive" (FDA label 12.1–12.2). This mechanism is different from benzodiazepines and Z-drugs (zopiclone, zolpidem), which boost the brain's main inhibitory chemical, GABA, more broadly. The mechanism matters for safety in two ways:

• Lower dependence signal. The US label says chronic use "did not produce withdrawal signs or symptoms" in animal studies and clinical trials. In 2026 the DEA, drawing on the HHS evaluation, found that the orexin antagonists "do not produce physical or psychological dependence", although their abuse potential "is similar to that of schedule IV substances" (DEA proposed rule).
• Narcolepsy-like effects. Narcolepsy type 1 is caused by a loss of orexin. Blocking orexin can therefore occasionally cause sleep paralysis, hallucinations at sleep onset or on waking, and brief cataplexy-like leg weakness. This is also why daridorexant is contraindicated in people with narcolepsy (EU SmPC 4.3–4.4).

Pharmacokinetics. Peak blood levels are reached in 1–2 hours. The terminal half-life is about 8 hours. The drug is 99.7% bound to plasma proteins, and 89% of its metabolism runs through the liver enzyme CYP3A4. That is why strong CYP3A4 inhibitors and inducers matter so much. A high-fat meal delays peak levels by 1.3 hours, which can delay sleep onset (FDA label 12.3).

What it is prescribed for

Licensed indications:

• UK/EU: adults with insomnia "characterised by symptoms present for at least 3 months and considerable impact on daytime functioning" (NICE, quoting the marketing authorisation).
• US: adults with insomnia "characterized by difficulties with sleep onset and/or sleep maintenance" (FDA label).
• It is not licensed for children, and its safety and effectiveness in children have not been established.

Where guidelines place it:

In short, daridorexant is a second-line option after CBTi in every guideline we reviewed. Its distinctive position in the UK is that NICE accepts it for longer-term use with regular review, which it does not for Z-drugs and benzodiazepines.

What works and what does not

Benefits by claim

1. The pivotal trials (manufacturer-funded)

Mignot et al. reported two randomised, double-blind, placebo-controlled phase 3 trials at 156 sites in 17 countries (Lancet Neurol 2022). The funding line of the paper reads simply "Idorsia Pharmaceuticals". Study 1 randomised 930 adults to 50 mg, 25 mg or placebo, and study 2 randomised 924 adults to 25 mg, 10 mg or placebo, each for 3 months. The primary outcomes were measured objectively in a sleep laboratory:

• 50 mg, WASO: least-squares mean difference versus placebo of −22.8 minutes (95% CI −28.0 to −17.6) at month 1 and −18.3 minutes (−23.9 to −12.7) at month 3.
• 50 mg, LPS: −11.4 minutes (−16.0 to −6.7) at month 1 and −11.7 minutes (−16.3 to −7.0) at month 3.
• 50 mg, self-reported total sleep time: +22.1 minutes at month 1 and +19.8 minutes (10.6 to 28.9) at month 3.
• 25 mg: WASO −11.9 minutes (study 1) and −10.3 minutes (study 2) at month 3. Self-reported total sleep time +9.9 and +19.1 minutes.
• 10 mg: no significant effect on WASO or LPS. This dose is not approved.

In the FDA label's tables for study 1, people on placebo also improved a lot. At month 3, WASO fell 11 minutes on placebo against 29 minutes on 50 mg, and self-reported total sleep time rose 38 minutes on placebo against 58 minutes on 50 mg (FDA label, Table 4). About two-thirds of the improvement in self-reported sleep time seen on 50 mg also happened on placebo. This is typical of insomnia trials, and it matters when people judge how much of their improvement is due to the tablet.

2. Is the difference clinically meaningful?

NICE's committee was candid about this. The Insomnia Severity Index (0–28, where higher is worse) was the only efficacy outcome in the company's economic model. On it, 50 mg reduced scores by 7.2 points against 5.4 on placebo at 3 months. The independent assessment group calculated a between-arm difference of −1.8. Clinical experts said "a difference of at least 4 in a between-arm analysis for ISI score would be considered clinically meaningful but noted that the placebo effect in this case was substantial." The committee concluded there was "uncertainty about whether the difference was clinically meaningful" (NICE 3.11, 3.36). The experts also argued that in practice only people who benefit would carry on, so the effect in real users might be larger. That is plausible, but it has not been tested.

For the objective measures, NICE's clinical experts said the WASO and LPS differences "can be considered clinically meaningful". They added that "in practice, subjective improvements in sleep quality, sleep quantity and daytime symptoms are more important" than laboratory measures.

3. Long-term use: what the extension really shows

The 40-week extension (study 303) enrolled 804 people who had completed the 12-week trials. Of these, 550 (68.4%) completed it (Kunz et al., CNS Drugs 2023). With 50 mg, self-reported total sleep time was higher than placebo by 20.4 minutes at week 12 of the extension (95% CI 4.2 to 36.5). At week 24 the difference was 15.8 minutes (−0.8 to 32.5) and at week 36 it was 17.8 minutes (−0.4 to 35.9). Both later confidence intervals cross zero. The extension was funded by Idorsia, which also paid for writing support, and four authors are Idorsia employees.

NICE's committee noted that "few participants remained on the daridorexant treatment arm at 12 months". The independent assessment group said benefits at 3 months "did not appear to persist at 12 months for some outcomes". The exact outcomes were marked confidential by the company (NICE 3.14, 3.17). An independent meta-analysis of all three orexin antagonists over 6 months or more found sustained subjective improvements. It also found more adverse events than placebo at 12 months and said longer trials are needed (Araujo et al., Arq Neuropsiquiatr 2026; no funding, no conflicts declared).

4. What independent syntheses conclude

• De Crescenzo et al., Lancet 2022 (NIHR-funded; 154 double-blind RCTs, 44,089 participants). This is the largest comparison and the one with the most public funding. It concluded that "many licensed drugs (including benzodiazepines, daridorexant, suvorexant, and trazodone) can be effective in the acute treatment of insomnia but are associated with poor tolerability, or information about long-term effects is not available." It found zopiclone caused more drop-outs from side effects than daridorexant (OR 3.45, 95% CI 1.41–8.33; low certainty). For long-term treatment, only eszopiclone and lemborexant beat placebo, with very low certainty (abstract).
• Yue et al., Sleep Med Rev 2023 (69 studies; authors declare no conflicts). Orexin antagonists ranked best for sleep latency, WASO, total sleep time and sleep efficiency. "Lemborexant and daridorexant ... showed greater efficacy than placebo ... with good tolerability." It also warned that "the long-term adverse effects of all medications are unclear" (abstract).
• Kishi et al., Transl Psychiatry 2025 (8 trials, 5,198 adults). All orexin antagonist arms outperformed placebo. Daridorexant 50 mg had the largest effect on self-reported total sleep time (reported SMD −0.475, 95% CI −0.593 to −0.357). Funding came from a university grant, but the authors have Eisai and Idorsia ties (full text).
• Smaller academic meta-analyses (no conflicts declared) broadly agree that daridorexant beats placebo. However, they found a modest rise in overall adverse events versus placebo: RR 1.16 in Tang et al. 2025 and RR 1.15 in Wang et al. 2026. Wang also found the benefit was clearest at 1 month. In people over 65, Rollo et al. (Sleep 2026) judged daridorexant's safety profile favourable. None of these reviews includes a head-to-head trial with another hypnotic.

How to read the disagreement. Smaller reviews that include only orexin antagonists and placebo tend to be positive. The broad Lancet review, which looked at acceptability and long-term data across 30 treatments, was more cautious. None of these reviews can add data that the manufacturer did not generate. All the daridorexant trials they pooled were Idorsia-funded.

Risks and all side effects

There is no boxed warning on the US label (FDA label). Complex sleep behaviours are nonetheless covered in its warnings section (see below).

Common side effects

In study 1 of the FDA label (reactions in at least 2% and more often than placebo), the rates on 25 mg / 50 mg / placebo were:

• headache: 6% / 7% / 5%
• somnolence or fatigue: 6% / 5% / 4%
• dizziness: 2% / 3% / 2%
• nausea: 0% / 3% / 2%

The EU SmPC lists headache, somnolence, dizziness, nausea and fatigue as common (1 in 100 to 1 in 10). It lists hypersensitivity, hallucinations, abnormal dreams or nightmares, sleepwalking (somnambulism) and sleep paralysis as uncommon (1 in 1,000 to 1 in 100) (EU SmPC 4.8). In study 1, adverse events of any kind occurred in 38% on 50 mg, 38% on 25 mg and 34% on placebo (Mignot 2022).

All interactions

This table is not a substitute for a pharmacist's interaction check. Tell your prescriber and pharmacist about every medicine, supplement and herbal product you take. Some herbal products can change liver-enzyme activity, and the daridorexant labels do not list every one.

Who should avoid daridorexant

• Contraindicated: narcolepsy; allergy to daridorexant or any ingredient; and, in the EU and UK, anyone taking strong CYP3A4 inhibitors (EU SmPC 4.3; FDA label 4).
• Severe liver impairment (Child-Pugh 10 or more): not studied and not recommended. In moderate impairment the maximum is 25 mg. No change is needed for kidney impairment, including severe.
• Pregnancy: there are no human data. The EU SmPC says to use it "only if the clinical condition of the pregnant woman requires treatment". Animal studies did not show harm. A US pregnancy registry is planned.
• Breastfeeding: it passes into milk in low amounts (0.02% of the maternal dose in the EU study). A risk of excessive sleepiness in the infant "cannot be excluded", so breastfed infants should be monitored.
• Older adults: no dose change is needed, but use caution because of fall risk. Data are limited over 75 years and absent over 85 years. The FDA notes somnolence becomes more likely with age. The 2023 AGS Beers Criteria do not list orexin antagonists, while they do tell older adults to avoid benzodiazepines and Z-drugs (AGS Beers 2023). An omission from the list is not an endorsement.
• Depression or other psychiatric conditions: use with caution, because data are limited and the trials excluded people needing psychiatric medicines.
• Severe COPD or significant breathing disorders: use with caution, because it has not been studied in severe COPD.
• History of alcohol or drug misuse: monitor carefully.
• Children and adolescents: not licensed. Safety and efficacy have not been established.
• Undiagnosed sleep problems: NICE's experts warned that sleep apnoea and restless legs can mimic insomnia. The US label says insomnia that has not improved after 7 to 10 days should prompt a check for another medical or psychiatric cause (NICE 3.5; FDA label 5.6).

Dosage and how to take it

Your prescriber sets the dose. The ranges below are the official licensed ranges for adults, given for information only.

• Food: it can be taken with or without food. A large or high-fat meal shortly beforehand can delay the effect on falling asleep.
• Missed dose: if you forget at bedtime, the EU SmPC says not to take it later in the night.
• How quickly it works: peak levels come 1–2 hours after a dose. In trials, effects were seen from the first nights and at month 1 (Wang et al. 2026; FDA label).
• Driving: the EU product information recommends about 9 hours between taking it and driving or using machines. Do not drive if you do not feel fully alert.
• Review: NICE expects a review within 3 months, and stopping if the response is not good enough.
• Stopping: the UK/EU licence says "treatment can be stopped without down-titration". No withdrawal or rebound was seen in trials, but the sleep benefit fades within days. Make any decision to stop, or to have a "drug holiday", with your prescriber, and ideally alongside CBTi.

Sleep habits and CBTi remain important while taking the medicine. NICE's committee said GPs should reinforce sleep hygiene advice alongside it, because neglecting behavioural measures may reduce the benefit (NICE 3.6, 3.17).

Follow the money: who makes it and who funded the evidence

Who makes and sells it

• Originator and marketer: Idorsia Ltd, Allschwil, Switzerland, listed on the SIX Swiss Exchange. Actelion created it in June 2017 as part of Johnson & Johnson's acquisition of Actelion (J&J SEC filing).
• Licence holders: Idorsia Pharmaceuticals Ltd holds the US application (FDA label). Idorsia Pharmaceuticals Deutschland GmbH, a German subsidiary, holds the EU and Great Britain licences (UK SmPC).
• Generics: none approved in the US as of this review.
• Revenue: Quviviq net sales were CHF 134 million in 2025, up from CHF 61 million in 2024. Idorsia's total revenue was CHF 221 million, with a US GAAP net loss of CHF 112 million. Total debt was CHF 1,342 million at the end of 2025, after a debt restructuring (Idorsia FY2025). Quviviq is the company's largest product line, so the company is under strong commercial pressure to grow it. That is a reason to read its claims critically. It is not proof that they are wrong.

Who funded the evidence

Every phase 3 trial of daridorexant was sponsored by Idorsia. The pivotal studies (Mignot 2022) list Idorsia as funder and include Idorsia employees as authors. The extension (Kunz 2023) was also funded by Idorsia, which paid for writing support and the open-access fee as well. NICE's appraisal rested on the company's submission. The independent assessment group's critique pulled the committee's preferred estimate to £25,383 per QALY, which NICE accepted as close enough to a stricter £25,000 threshold that it chose because of the remaining uncertainty (NICE 3.37–3.39). The independent reviews were paid for by public or academic sources: NIHR (UK), the National Research Foundation of Korea, the Taiwanese science ministry, and university grants. Some of their authors nevertheless declare industry ties, including to makers of competing orexin drugs. The scorecard above and the source list set these out.

Influence on guidelines and regulation (documented, not insinuated)

• The American Academy of Sleep Medicine disclosed $60,000 from Idorsia and $20,000 from Eisai under its 2023 Industry Engagement Program (AASM disclosure). Members of its 2026 insomnia combination-treatment panel declare current or recent consulting for Idorsia and Eisai (Buysse et al. 2026). That guideline's recommendations favour CBTi and do not promote any specific drug.
• US scheduling: on 3 April 2023 Idorsia petitioned the DEA to remove the three orexin antagonists from federal control altogether, and Eisai sent a letter supporting the petition. The DEA has not granted full descheduling. Instead, after an HHS evaluation, it proposed in August 2026 to move them from Schedule IV to Schedule V (Federal Register). Lobbying for a regulatory change is legal and was disclosed. The independent HHS and DEA review, rather than the petition, is the relevant evidence on dependence.
• Integrity events: in the sources we fetched, we found no retractions, regulatory sanctions or data-integrity findings relating to daridorexant.

Related research

• Sleep prevention guide: CBTi principles, sleep timing and non-drug steps that every guideline puts first.
• Sleep supplements: independent evidence
• Melatonin: a timing signal rather than a sedative; prescription prolonged-release melatonin is another insomnia option in over-55s.
• Magnesium and L-theanine
• Stress, anxiety and depression prevention guide: insomnia and mood problems often occur together.
• Stress, anxiety and depression supplements evidence
• St John's wort: a CYP3A4 inducer that can interact with many prescription drugs.
• Other prescription sleep medicines: zopiclone, zolpidem, trazodone, mirtazapine

Frequently asked questions

Sources and funding notes

• NICE TA922, Recommendations (18 Oct 2023): UK health technology appraisal. The recommendation rests on a company (Idorsia) submission.
• NICE TA922, Information about daridorexant: indication and list price (from the company submission).
• NICE TA922, Committee discussion: evidence submitted by Idorsia and critiqued by an independent external assessment group. Some 12-month data were withheld as confidential by the company.
• EMA, Quviviq EPAR overview: EU regulator (about 91.5% of its 2026 budget comes from fees).
• EMA, Quviviq product information (SmPC), updated 12 Mar 2026: regulator-approved text. Licence holder Idorsia Pharmaceuticals Deutschland GmbH.
• EMA, Funding page: sets out the agency's reliance on fees (EU).
• Quviviq 25 mg UK SmPC (emc): GB licence PLGB 48711/0002. Prescription-only medicine. Company-maintained, regulator-approved text.
• FDA prescribing information for Quviviq (DailyMed, version dated 26 Feb 2026): US regulator-approved label. Applicant Idorsia Pharmaceuticals Ltd.
• Drugs@FDA, NDA 214985: approval 7 Jan 2022, new molecular entity (US government).
• openFDA Drugs@FDA query: no ANDA (generic) records found (US government).
• DEA, Notice of proposed rulemaking: rescheduling suvorexant, lemborexant and daridorexant to Schedule V (Federal Register 91 FR 51606, 11 Aug 2026): US Department of Justice, relying on the HHS evaluation. It records Idorsia's 2023 descheduling petition.
• Mignot E et al., Lancet Neurol 2022 (phase 3 studies 1 and 2): funded by Idorsia Pharmaceuticals (Switzerland). Two Idorsia employee authors, and several authors with Idorsia fees or grants.
• Kunz D et al., CNS Drugs 2023 (40-week extension): funded by Idorsia, including writing support and the open-access fee. Four Idorsia employee authors, and the others are Idorsia advisory board members.
• De Crescenzo F et al., Lancet 2022 (network meta-analysis): funded by UK NIHR Oxford Health BRC and MRC (public). Declared ties to Boehringer Ingelheim (employment), Janssen (seltorexant trials) and Angelini.
• Kishi T et al., Transl Psychiatry 2025 (NMA of orexin antagonists): Fujita Health University grant (Japan). Authors report Eisai grants and honoraria, and a co-author consults for Idorsia, Eisai and Merck.
• Yue JL et al., Sleep Med Rev 2023 (NMA): China. Authors declare no conflicts. Funding not stated in the abstract.
• Hasan F et al., Sleep Breath 2023 (NMA, adults 18–65): funded by the Ministry of Science and Technology, Taiwan (public). It called daridorexant "a promising agent" for sleep-maintenance insomnia.
• Tang M et al., Psychopharmacology 2025: indirect comparison of lemborexant and daridorexant. No conflicts declared.
• Wang X et al., Front Pharmacol 2026: dose and time-course meta-analysis. No conflicts declared.
• Araujo LMM et al., Arq Neuropsiquiatr 2026: long-term orexin antagonist meta-analysis (Brazil). No funding and no conflicts.
• Rollo E et al., Sleep 2026: orexin antagonists in older adults (Italy). Financial disclosure: none.
• Na HJ et al., Sleep 2024: safety and narcolepsy-like symptoms. Funded by the National Research Foundation of Korea (public).
• Pan G et al., J Psychiatr Res 2024: falls and fractures meta-analysis (China). No competing interests.
• Fornaro M et al., Eur Neuropsychopharmacol 2024: driving NMA (Italy/Spain). Several authors declare industry fees, one including Idorsia.
• Riemann D et al., J Sleep Res 2023 (European Insomnia Guideline): European Sleep Research Society. Author conflicts not verified because the publisher page was inaccessible.
• Qaseem A et al., Ann Intern Med 2016 (ACP guideline): American College of Physicians (US), funded from its own budget.
• Sateia MJ et al., J Clin Sleep Med 2017 (AASM pharmacologic guideline): funded by the AASM (US). Predates daridorexant.
• Buysse DJ et al., J Clin Sleep Med 2026 (AASM combination-treatment guideline): AASM (US). Panel members declare Idorsia and Eisai consulting.
• AASM, CMSS financial disclosure (2023): self-disclosure. Idorsia $60,000 and Eisai $20,000.
• American Geriatrics Society, 2023 Beers Criteria: professional society (US). No sponsor for the paper. Orexin antagonists are not listed.
• NHS, Insomnia (reviewed 19 Mar 2024): UK public health service.
• Johnson & Johnson, SEC Form 8-K exhibit (16 Jun 2017): company filing (US) recording the creation of Idorsia from Actelion.
• Idorsia, Full-year 2025 results (26 Feb 2026): company release (Switzerland). Figures are reliable, but the framing is promotional.

Last reviewed: 26 September 2026. Educational information from Pure City Research, not medical advice. Medicine decisions belong with a qualified prescriber.