Daridorexant Evidence: Trial Results and Peer-Reviewed Publications

Hipa.ai Research · Source: PubMed & ClinicalTrials.gov / AACT · Last updated:

The clinical evidence base for Daridorexant comprises 47 peer-reviewed publications across 15 journals, 9 pivotal-trial primary-outcome rows reported to ClinicalTrials.gov, spanning indications including Sleep Initiation and Maintenance Disorders, and Stress Disorders, Post-Traumatic. Most recent publication: Efficacy and safety of daridorexant for the treatment of insomnia disorder in women of menopausal transition age: Insights from a randomized controlled trial., Maturitas, 2026.

Top peer-reviewed publications

Curated set of pivotal-trial result papers and recent publications in high-tier journals.

  1. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials.
    Mignot E, Mayleben D, Fietze I, et al. · Lancet Neurol · 2022
    PubMed: PMID 35065036 · NCT03545191 · Sleep Initiation and Maintenance Disorders
  2. Efficacy and safety of daridorexant for the treatment of insomnia disorder in women of menopausal transition age: Insights from a randomized controlled trial.
    Schaedel Z, Bakker TR, Bassetti C, et al. · Maturitas · 2026
    PubMed: PMID 41506007 · NCT03545191 · Sleep Initiation and Maintenance Disorders
  3. The Insomnia EEG Score: a new tool for the classification of people with poor sleep.
    Pathmanathan J, Little D, Sadeghi K, et al. · Sleep · 2026
    PubMed: PMID 41217192 · NCT03545191 · Sleep Initiation and Maintenance Disorders
  4. Nighttime safety of daridorexant: Evaluation of responsiveness to an external noise stimulus, postural stability, walking, and cognitive function.
    Magliocca M, Koopmans I, Vaillant C, et al. · J Psychopharmacol · 2025
  5. The Effects of Daridorexant on Patients With Comorbid Insomnia Disorder and Untreated Mild Obstructive Sleep Apnoea: A Post Hoc Subgroup Analysis of a Phase 3, Randomised Clinical Trial.
    Lettieri CJ, Briasoulis O, Léger D, et al. · J Sleep Res · 2026
    PubMed: PMID 40660750 · NCT03545191 · Sleep Initiation and Maintenance Disorders
  6. Efficacy and safety of daridorexant in Chinese patients with insomnia disorder: a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial.
    Huang Z, Wang H, Zhang B, et al. · Sleep · 2025
    PubMed: PMID 40557879 · NCT06010693 · Sleep Initiation and Maintenance Disorders
  7. Daridorexant in severe obstructive sleep apnea: Effects on sleep-disordered breathing and sleep.
    Fietze I, Boof ML, Lederer K, et al. · Sleep · 2026
  8. Daridorexant in children and adolescents with insomnia disorder: study protocol for a multicentre randomised controlled trial.
    Coloma P, Coury D, Wernette S, et al. · BMJ Open · 2026
    PubMed: PMID 41942161 · NCT05423717 · Sleep Initiation and Maintenance Disorders

Primary-outcome results across pivotal trials

Per-arm reported values from Phase 2/3 and Phase 3 trials with results posted to ClinicalTrials.gov.

TrialIndicationPrimary endpointArmValue
NCT03545191Sleep Initiation and Maintenance DisordersChange From Baseline to Month 1 in Latency to Persistent Sleep (LPS) (Sleep Onset)
From baseline to Month 1 (i.e. for up to 1 month)
Daridorexant 25 mg-28.17 minutes
Daridorexant 50 mg-31.20 minutes
Placebo-19.85 minutes
NCT03545191Sleep Initiation and Maintenance DisordersChange From Baseline to Month 1 in Wake After Sleep Onset (WASO) (Sleep Maintenance)
From baseline to Month 1 (i.e. for up to 1 month)
Daridorexant 25 mg-18.40 minutes
Daridorexant 50 mg-28.98 minutes
Placebo-6.20 minutes
NCT03545191Sleep Initiation and Maintenance DisordersChange From Baseline to Month 3 in Latency to Persistent Sleep (LPS)
From baseline to Month 3 (i.e. for up to 3 months)
Daridorexant 25 mg-30.73 minutes
Daridorexant 50 mg-34.80 minutes
Placebo-23.13 minutes
NCT03545191Sleep Initiation and Maintenance DisordersChange From Baseline to Month 3 in Wake After Sleep Onset (WASO)
From baseline to Month 3 (i.e. for up to 3 months)
Daridorexant 25 mg-22.97 minutes
Daridorexant 50 mg-29.41 minutes
Placebo-11.11 minutes
NCT03575104Sleep Initiation and Maintenance DisordersChange From Baseline to Month 1 in Latency to Persistent Sleep (LPS) (Sleep Onset)
From baseline to Month 1 (i.e. for up to 1 month)
Daridorexant 10 mg-22.62 minutes
Daridorexant 25 mg-26.46 minutes
Placebo-20.01 minutes
NCT03575104Sleep Initiation and Maintenance DisordersChange From Baseline to Month 1 in Wake After Sleep Onset (WASO) (Sleep Maintenance)
From baseline to Month 1 (i.e. for up to 1 month)
Daridorexant 10 mg-15.31 minutes
Daridorexant 25 mg-24.19 minutes
Placebo-12.57 minutes
NCT03575104Sleep Initiation and Maintenance DisordersChange From Baseline to Month 3 in Latency to Persistent Sleep (LPS)
From baseline to Month 3 (i.e. for up to 3 months)
Daridorexant 10 mg-23.09 minutes
Daridorexant 25 mg-28.91 minutes
Placebo-19.89 minutes
NCT03575104Sleep Initiation and Maintenance DisordersChange From Baseline to Month 3 in Wake After Sleep Onset (WASO)
From baseline to Month 3 (i.e. for up to 3 months)
Daridorexant 10 mg-15.95 minutes
Daridorexant 25 mg-24.25 minutes
Placebo-14.00 minutes
NCT03679884Sleep Initiation and Maintenance DisordersTotal no. of Subjects With at Least One TEAE
TEAEs (AEs that started or worsened during the double-blind study period up to 30 days after double-blind study treatment end date) are reported. Total duration: up to 44 weeks.
Daridorexant 10 mg53 Participants
Daridorexant 25 mg103 Participants
Daridorexant 50 mg55 Participants
ExPlacebo / Daridorexant 25 mg48 Participants
Placebo45 Participants

Publications by year

19932026: 47 publications.

1993
1
2007
1
2010
1
2011
1
2012
1
2019
2
2020
1
2021
6
2022
5
2023
9
2024
8
2025
6
2026
5

Publications by indication

Sleep Initiation and Maintenance Disorders (41)

  • Efficacy and safety of daridorexant for the treatment of insomnia disorder in women of menopausal transition age: Insights from a randomized controlled trial.
    Maturitas · 2026 · PMID 41506007 · NCT03545191
  • The Insomnia EEG Score: a new tool for the classification of people with poor sleep.
    Sleep · 2026 · PMID 41217192 · NCT03545191
  • The Effects of Daridorexant on Patients With Comorbid Insomnia Disorder and Untreated Mild Obstructive Sleep Apnoea: A Post Hoc Subgroup Analysis of a Phase 3, Randomised Clinical Trial.
    J Sleep Res · 2026 · PMID 40660750 · NCT03545191
  • Daridorexant in children and adolescents with insomnia disorder: study protocol for a multicentre randomised controlled trial.
    BMJ Open · 2026 · PMID 41942161 · NCT05423717
  • Efficacy and safety of daridorexant in Chinese patients with insomnia disorder: a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial.
    Sleep · 2025 · PMID 40557879 · NCT06010693

Stress Disorders, Post-Traumatic (1)

  • Allocation in platform trials to maintain comparability across time and eligibility.
    Stat Med · 2023 · PMID 37088912 · NCT05948540

Publications by journal

Trial-results highlights

In a clinical trial for sleep initiation and maintenance disorders, NCT03545191, participants received Daridorexant or placebo. At Month 1, the change from baseline in Latency to Persistent Sleep (LPS), which measures sleep onset, was observed as:

  • -28.17 minutes for the Daridorexant 25 mg arm
  • -31.20 minutes for the Daridorexant 50 mg arm
  • -19.85 minutes for the placebo arm

For Wake After Sleep Onset (WASO), which measures sleep maintenance, the change from baseline at Month 1 was:

  • -18.40 minutes for the Daridorexant 25 mg arm
  • -28.98 minutes for the Daridorexant 50 mg arm
  • -6.20 minutes for the placebo arm

At Month 3, the change from baseline in LPS was:

  • -30.73 minutes for the Daridorexant 25 mg arm
  • -34.80 minutes for the Daridorexant 50 mg arm

All Daridorexant publications (47)

2026 (5 papers)

  1. Efficacy and safety of daridorexant for the treatment of insomnia disorder in women of menopausal transition age: Insights from a randomized controlled trial.
    Schaedel Z, Bakker TR, Bassetti C, et al. · Maturitas · 2026 · Derived
    PubMed: PMID 41506007 · NCT03545191 · Sleep Initiation and Maintenance Disorders
  2. The Insomnia EEG Score: a new tool for the classification of people with poor sleep.
    Pathmanathan J, Little D, Sadeghi K, et al. · Sleep · 2026 · Derived
    PubMed: PMID 41217192 · NCT03545191 · Sleep Initiation and Maintenance Disorders
  3. The Effects of Daridorexant on Patients With Comorbid Insomnia Disorder and Untreated Mild Obstructive Sleep Apnoea: A Post Hoc Subgroup Analysis of a Phase 3, Randomised Clinical Trial.
    Lettieri CJ, Briasoulis O, Léger D, et al. · J Sleep Res · 2026 · Derived
    PubMed: PMID 40660750 · NCT03545191 · Sleep Initiation and Maintenance Disorders
  4. Daridorexant in severe obstructive sleep apnea: Effects on sleep-disordered breathing and sleep.
    Fietze I, Boof ML, Lederer K, et al. · Sleep · 2026 · Derived
  5. Daridorexant in children and adolescents with insomnia disorder: study protocol for a multicentre randomised controlled trial.
    Coloma P, Coury D, Wernette S, et al. · BMJ Open · 2026 · Derived
    PubMed: PMID 41942161 · NCT05423717 · Sleep Initiation and Maintenance Disorders

2025 (6 papers)

  1. Nighttime safety of daridorexant: Evaluation of responsiveness to an external noise stimulus, postural stability, walking, and cognitive function.
    Magliocca M, Koopmans I, Vaillant C, et al. · J Psychopharmacol · 2025 · Derived
  2. Efficacy and safety of daridorexant in Chinese patients with insomnia disorder: a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial.
    Huang Z, Wang H, Zhang B, et al. · Sleep · 2025 · Derived
    PubMed: PMID 40557879 · NCT06010693 · Sleep Initiation and Maintenance Disorders
  3. Effect of daridorexant on nighttime wakefulness and next-morning sleepiness: assessing the transition from night to day in insomnia disorder.
    Dauvilliers Y, Braunstein G, Zammit G, et al. · Sleep Med · 2025 · Derived
    PubMed: PMID 40288253 · NCT03545191 · Sleep Initiation and Maintenance Disorders
  4. Clinical practice guidelines for switching or deprescribing hypnotic medications for chronic insomnia: Results of European neuropsychopharmacology and sleep expert's consensus group.
    Palagini L, Brugnoli R, Dell' Osso BM, et al. · Sleep Med · 2025 · Background
    PubMed: PMID 39923608 · NCT07555743 · Sleep Initiation and Maintenance Disorders
  5. Efficacy of orexin antagonists for the management of major depressive disorder: A systematic review of randomized clinical trials.
    Meshkat S, Kwan ATH, Le GH, et al. · J Affect Disord · 2025 · Background
    PubMed: PMID 39638064 · NCT07555743 · Sleep Initiation and Maintenance Disorders
  6. Conditions of sleep restoration after smoking cessation: A systematic review.
    Mauries S, Rolland B, Mallevays M, et al. · Sleep Med Rev · 2025 · Background
    PubMed: PMID 39893864 · NCT07328594 · Sleep Initiation and Maintenance Disorders

2024 (8 papers)

  1. Effect of Daridorexant on the Pharmacokinetics of Midazolam, and on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Male Subjects.
    Zenklusen I, Dingemanse J, Reh C, et al. · Drugs R D · 2024 · Derived
  2. Meaningful Within-Patient Change in Subjective Total Sleep Time in Patients with Insomnia Disorder: An Analysis of the Sleep Diary Questionnaire Using Data from Open-Label and Phase III Clinical Trials.
    Phillips-Beyer A, Kawata AK, Kleinman L, et al. · Pharmaceut Med · 2024 · Derived
    PubMed: PMID 38302765 · NCT03545191 · Sleep Initiation and Maintenance Disorders
  3. Effect of daridorexant on sleep architecture in patients with chronic insomnia disorder: a pooled post hoc analysis of two randomized phase 3 clinical studies.
    Di Marco T, Djonlagic I, Dauvilliers Y, et al. · Sleep · 2024 · Derived
    PubMed: PMID 38644625 · NCT03575104 · Sleep Initiation and Maintenance Disorders
  4. Orexin Receptor Antagonists as Adjunct Drugs for the Treatment of Depression: A Mini Meta-Analysis.
    Uğurlu M · Noro Psikiyatr Ars · 2024 · Background
    PubMed: PMID 38496221 · NCT07555743 · Sleep Initiation and Maintenance Disorders
  5. Effects of Approved Pharmacological Interventions for Insomnia on Mood Disorders: A Systematic Review.
    Palagini L, Miniati M, Marazziti D, et al. · Clin Neuropsychiatry · 2024 · Background
    PubMed: PMID 39540072 · NCT07555743 · Sleep Initiation and Maintenance Disorders
  6. Early experience with the new DORA daridorexant in patients with insomnia disorder and comorbid mental disturbances: Results of a naturalistic study with 3 months follow-up.
    Palagini L, Alfi G, Gurrieri R, et al. · J Sleep Res · 2024 · Background
    PubMed: PMID 38522432 · NCT07555743 · Sleep Initiation and Maintenance Disorders
  7. Clinical safety and narcolepsy-like symptoms of dual orexin receptor antagonists in patients with insomnia: a systematic review and meta-analysis.
    Na HJ, Jeon N, Staatz CE, et al. · Sleep · 2024 · Background
    PubMed: PMID 37950346 · NCT07555743 · Sleep Initiation and Maintenance Disorders
  8. A narrative review on insomnia and hypersomnolence within Major Depressive Disorder and bipolar disorder: A proposal for a novel psychometric protocol.
    Guerrera CS, Boccaccio FM, Varrasi S, et al. · Neurosci Biobehav Rev · 2024 · Background
    PubMed: PMID 38331126 · NCT07555743 · Sleep Initiation and Maintenance Disorders

2023 (9 papers)

  1. Meaningful Within-Patient Change on the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ): Analysis of Phase III Clinical Trial Data of Daridorexant.
    Phillips-Beyer A, Kawata AK, Kleinman L, et al. · Pharmaceut Med · 2023 · Derived
    PubMed: PMID 37286927 · NCT03545191 · Sleep Initiation and Maintenance Disorders
  2. Long-Term Safety and Tolerability of Daridorexant in Patients with Insomnia Disorder.
    Kunz D, Dauvilliers Y, Benes H, et al. · CNS Drugs · 2023 · Derived
    PubMed: PMID 36484969 · NCT03679884 · Sleep Initiation and Maintenance Disorders
  3. Daridorexant as a novel pharmacotherapeutic approach in insomnia: a systematic review and meta-analysis.
    Dutta S, Singhal S, Shah R, et al. · Expert Opin Drug Saf · 2023 · Derived
    PubMed: PMID 37526060 · NCT03545191 · Sleep Initiation and Maintenance Disorders
  4. Number, Duration, and Distribution of Wake Bouts in Patients with Insomnia Disorder: Effect of Daridorexant and Zolpidem.
    Di Marco T, Scammell TE, Meinel M, et al. · CNS Drugs · 2023 · Derived
    PubMed: PMID 37477771 · NCT03545191 · Sleep Initiation and Maintenance Disorders
  5. Lemborexant and Daridorexant for the Treatment of Insomnia: An Indirect Comparison Using Number Needed to Treat, Number Needed to Harm, and Likelihood to Be Helped or Harmed.
    Citrome L, Juday TR, Lundwall C, et al. · J Clin Psychiatry · 2023 · Derived
    PubMed: PMID 37796657 · NCT03545191 · Sleep Initiation and Maintenance Disorders
  6. Effect of Daridorexant on the Pharmacokinetics of P-Glycoprotein Substrate Dabigatran Etexilate and Breast Cancer Resistance Protein Substrate Rosuvastatin in Healthy Subjects.
    Anliker-Ort M, Dingemanse J, Janů L, et al. · Clin Drug Investig · 2023 · Derived
  7. Alliance for Sleep Clinical Practice Guideline on Switching or Deprescribing Hypnotic Medications for Insomnia.
    Watson NF, Benca RM, Krystal AD, et al. · J Clin Med · 2023 · Background
    PubMed: PMID 37048577 · NCT07555743 · Sleep Initiation and Maintenance Disorders
  8. Allocation in platform trials to maintain comparability across time and eligibility.
    Viele K · Stat Med · 2023 · Background
    PubMed: PMID 37088912 · NCT05948540 · Stress Disorders, Post-Traumatic
  9. Orexin Receptor Antagonists in the Treatment of Depression: A Leading Article Summarising Pre-clinical and Clinical Studies.
    Fagan H, Jones E, Baldwin DS, et al. · CNS Drugs · 2023 · Background
    PubMed: PMID 36436175 · NCT07555743 · Sleep Initiation and Maintenance Disorders

2022 (5 papers)

  1. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials.
    Mignot E, Mayleben D, Fietze I, et al. · Lancet Neurol · 2022 · Trial result
    PubMed: PMID 35065036 · NCT03545191 · Sleep Initiation and Maintenance Disorders
  2. Preferences of patients for benefits and risks of insomnia medications using data elicited during two phase III clinical trials.
    Heidenreich S, Ross M, Chua GN, et al. · Sleep · 2022 · Derived
    PubMed: PMID 36054921 · NCT03545191 · Sleep Initiation and Maintenance Disorders
  3. Efficacy and Safety of Daridorexant in Older and Younger Adults with Insomnia Disorder: A Secondary Analysis of a Randomised Placebo-Controlled Trial.
    Fietze I, Bassetti CLA, Mayleben DW, et al. · Drugs Aging · 2022 · Derived
    PubMed: PMID 36098936 · NCT03545191 · Sleep Initiation and Maintenance Disorders
  4. Effect of insomnia in the major depressive disorder.
    Xu G, Li X, Xu C, et al. · BMC Neurol · 2022 · Background
    PubMed: PMID 36088310 · NCT07555743 · Sleep Initiation and Maintenance Disorders
  5. Dual Orexin Receptor Antagonists (DORAs) as an Adjunct Treatment for Smoking Cessation.
    Hamidovic A · CNS Drugs · 2022 · Background
    PubMed: PMID 35451800 · NCT07328594 · Sleep Initiation and Maintenance Disorders

2021 (6 papers)

  1. Impact of Daridorexant, a Dual Orexin Receptor Antagonist, on Cardiac Repolarization Following Bedtime Dosing: Results from a Thorough QT Study Using Concentration-QT Analysis.
    Schilling U, Henrich A, Muehlan C, et al. · Clin Drug Investig · 2021 · Derived
  2. Development and Validation of the Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ).
    Hudgens S, Phillips-Beyer A, Newton L, et al. · Patient · 2021 · Background
    PubMed: PMID 33131027 · NCT03575104 · Sleep Initiation and Maintenance Disorders
  3. Real-world evidence from a European cohort study of patients with treatment resistant depression: Treatment patterns and clinical outcomes.
    Heerlein K, Perugi G, Otte C, et al. · J Affect Disord · 2021 · Background
    PubMed: PMID 34044256 · NCT07555743 · Sleep Initiation and Maintenance Disorders
  4. The Economic Burden of Adults with Major Depressive Disorder in the United States (2010 and 2018).
    Greenberg PE, Fournier AA, Sisitsky T, et al. · Pharmacoeconomics · 2021 · Background
    PubMed: PMID 33950419 · NCT07555743 · Sleep Initiation and Maintenance Disorders
  5. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.
    GBD 2019 Diseases and Injuries Collaborators · Lancet · 2021 · Background
    PubMed: PMID 33069326 · NCT07555743 · Sleep Initiation and Maintenance Disorders
  6. The Insomnia-Addiction Positive Feedback Loop: Role of the Orexin System.
    Fragale JE, James MH, Avila JA, et al. · Front Neurol Neurosci · 2021 · Background
    PubMed: PMID 34052815 · NCT07328594 · Sleep Initiation and Maintenance Disorders

2020 (1 paper)

  1. Hypnotic Discontinuation in Chronic Insomnia.
    Hintze JP, Edinger JD · Sleep Med Clin · 2020 · Background
    PubMed: PMID 32386690 · NCT07555743 · Sleep Initiation and Maintenance Disorders

2019 (2 papers)

  1. Insomnia as an independent predictor of suicide attempts: a nationwide population-based retrospective cohort study.
    Lin HT, Lai CH, Perng HJ, et al. · BMC Psychiatry · 2019 · Background
    PubMed: PMID 29716570 · NCT07555743 · Sleep Initiation and Maintenance Disorders
  2. Reduced Orexin System Function Contributes to Resilience to Repeated Social Stress.
    Grafe LA, Eacret D, Dobkin J, et al. · eNeuro · 2019 · Background
    PubMed: PMID 29662948 · NCT07555743 · Sleep Initiation and Maintenance Disorders

2012 (1 paper)

  1. Hypocretin modulation of drug-induced synaptic plasticity.
    Baimel C, Borgland SL · Prog Brain Res · 2012 · Background
    PubMed: PMID 22813972 · NCT07555743 · Sleep Initiation and Maintenance Disorders

2011 (1 paper)

  1. Hcrtr1 and 2 signaling differentially regulates depression-like behaviors.
    Scott MM, Marcus JN, Pettersen A, et al. · Behav Brain Res · 2011 · Background
    PubMed: PMID 21377495 · NCT07555743 · Sleep Initiation and Maintenance Disorders

2010 (1 paper)

  1. Treatment of insomnia in depressed insomniacs: effects on health-related quality of life, objective and self-reported sleep, and depression.
    McCall WV, Blocker JN, D'Agostino R, et al. · J Clin Sleep Med · 2010 · Background
    PubMed: PMID 20726279 · NCT07555743 · Sleep Initiation and Maintenance Disorders

2007 (1 paper)

  1. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report.
    Rush AJ, Trivedi MH, Wisniewski SR, et al. · Am J Psychiatry · 2007 · Background
    PubMed: PMID 17074942 · NCT07555743 · Sleep Initiation and Maintenance Disorders

1993 (1 paper)

  1. Dysfunctional beliefs and attitudes about sleep among older adults with and without insomnia complaints.
    Morin CM, Stone J, Trinkle D, et al. · Psychol Aging · 1993 · Background
    PubMed: PMID 8216967 · NCT07555743 · Sleep Initiation and Maintenance Disorders

Sources and methodology

This page summarizes published evidence for general reference and does not constitute medical advice. For clinical decisions, consult the linked primary publications and your healthcare provider. Data sourced from PubMed and the ClinicalTrials.gov / AACT database maintained by the Clinical Trials Transformation Initiative (CTTI).