{ "artifact": "PV literature screening record", "artifact_version": "1.0", "counts": { "accounts_for_every_retrieved_record": true, "n_excluded": 37, "n_excluded_by_reason_code": { "X2": 20, "X3": 1, "X4": 14, "X6": 2 }, "n_included": 23, "n_retrieved": 60, "total_reported_by_esearch": 60 }, "flagged_candidates": [ { "citation": "Sun D, Li J, Chen G, Liu X, Jiang C, Ye T. Suicidal ideation associated with daridorexant treatment in insomnia patients: Comparator-restricted disproportionality analysis and assessment of potential heterogeneity in reporting patterns.. Social psychiatry and psychiatric epidemiology. 2026:10.1007/s00127-026-03227-9. doi:10.1016/j.jclinepi.2023.08.010 PMID:42888253.", "doi": "10.1016/j.jclinepi.2023.08.010", "languages": [ "eng" ], "pmid": "42888253", "publication_types": [ "journal article" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42888253/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "Suicidal ideation associated with daridorexant treatment in insomnia patients: Comparator-restricted disproportionality analysis and assessment of potential heterogeneity in reporting patterns.", "Although previous studies have identified a significant signal for suicidal ideation associated with daridorexant when compared with all other drugs, the significance when compared specifically with insomnia medications and the potential differences in reporting patterns of suicidal ideation across subgroups remain unclear.", "Additionally, there may be potential differences in reporting patterns of daridorexant-associated suicidal ideation across subgroups." ] }, { "citation": "Svedmyr S, Bergqvist J. Daridorexant- Case Report of Possible Side-Effect in Rare Mitochondrial Disorder.. Journal of sleep research. 2026:e70440. doi:10.1111/jsr.70440 PMID:42674807.", "doi": "10.1111/jsr.70440", "languages": [ "eng" ], "pmid": "42674807", "publication_types": [ "journal article" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42674807/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "Daridorexant- Case Report of Possible Side-Effect in Rare Mitochondrial Disorder." ] }, { "citation": "Fietze I, Boof ML, Lederer K, Lemoine V, Vaillant C, Pépin JL. Daridorexant in severe obstructive sleep apnea: effects on sleep-disordered breathing and sleep.. Sleep. 2026;49(9):zsag145. doi:10.5664/jcsm.9300 PMID:42171662.", "doi": "10.5664/jcsm.9300", "languages": [ "eng" ], "pmid": "42171662", "publication_types": [ "clinical trial, phase i", "journal article", "randomized controlled trial" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/42171662/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "Four adverse events were reported (daridorexant n = 3;" ] }, { "citation": "Schaedel Z, Bakker TR, Bassetti C, Briasoulis O, Cassel P, Pain S, et al. 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;206:108821. doi:10.1016/j.maturitas.2025.108821 PMID:41506007.", "doi": "10.1016/j.maturitas.2025.108821", "languages": [ "eng" ], "pmid": "41506007", "publication_types": [ "journal article", "randomized controlled trial", "multicenter study" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41506007/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "Efficacy and safety of daridorexant for the treatment of insomnia disorder in women of menopausal transition age: Insights from a randomized controlled trial.", "OBJECTIVES: To evaluate the efficacy and safety of daridorexant in women aged 47-55 years with insomnia disorder, an age group representative of the menopause transition.", "Daridorexant 50 mg is well tolerated in this population, with no increased risk of next-morning sleepiness or somnolence." ] }, { "citation": "Kono S, Nishiyama T, Nakano S, Ishimoto Y, Horikoshi S. Real-World Effectiveness and Safety of Daridorexant in Japanese Patients With Insomnia: A Multicenter Observational Study Evaluating Four-Week Changes in Athens Insomnia Scale Among 54 Participants.. Cureus. 2025;17(11):e97174. doi:10.7759/cureus.97174 PMID:41262489.", "doi": "10.7759/cureus.97174", "languages": [ "eng" ], "pmid": "41262489", "publication_types": [ "journal article" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41262489/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "Real-World Effectiveness and Safety of Daridorexant in Japanese Patients With Insomnia: A Multicenter Observational Study Evaluating Four-Week Changes in Athens Insomnia Scale Among 54 Participants.", "Therefore, this observational study assessed the effectiveness and safety of daridorexant in real-world settings for Japanese participants with insomnia beyond those evaluated in previous clinical trials." ] }, { "citation": "Pathmanathan J, Little D, Sadeghi K, Di Marco T, Kleinschmidt D, Nerrie J, et al. The Insomnia EEG Score: a new tool for the classification of people with poor sleep.. Sleep. 2026;49(4):zsaf353. doi:10.1093/sleep/zsaf353 PMID:41217192.", "doi": "10.1093/sleep/zsaf353", "languages": [ "eng" ], "pmid": "41217192", "publication_types": [ "journal article" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/41217192/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "Clinical Trials Study to Assess the Efficacy and Safety of ACT-541468 (Daridorexant) in Adult and Elderly Subjects with Insomnia Disorder, https://clinicaltrials.gov/study/NCT03545191, NCT03545191;", "Study to Assess the Efficacy and Safety of ACT-541468 (Daridorexant) in Adult and Elderly Subjects Suffering from Difficulties to Sleep, https://www.clinicaltrials.gov/study/NCT03575104, NCT03575104." ] }, { "citation": "Ferini-Strambi L, Arnaldi D, Bonanni E, Cicolin A, Gigli GL, Liguori C, et al. Daridorexant and Insomnia in Clinical Practice: A Nominal Group Technique Consensus Study among Italian Sleep and Insomnia Experts.. Current neuropharmacology. 2026;24(1):135-149. doi:10.1016/j.smrv.2023.101762 PMID:40776640.", "doi": "10.1016/j.smrv.2023.101762", "languages": [ "eng" ], "pmid": "40776640", "publication_types": [ "consensus statement", "journal article" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/40776640/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "Key findings highlight daridorexant's mechanism of action, safety profile, efficacy on night and day parameters, and suitability for long-term use.", "DISCUSSION: Daridorexant may address insomnia without increasing sedation via its dual orexin receptor antagonism." ] }, { "citation": "Lettieri CJ, Briasoulis O, Léger D, Luyet PP, Pépin JL, Quan SF, et al. 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.. Journal of sleep research. 2026;35(2):e70135. doi:10.5664/jcsm.7112 PMID:40660750.", "doi": "10.5664/jcsm.7112", "languages": [ "eng" ], "pmid": "40660750", "publication_types": [ "journal article", "clinical trial, phase iii", "randomized controlled trial", "research support, non-u.s. gov't" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/40660750/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "This post hoc analysis evaluated the efficacy and safety of daridorexant 25 and 50 mg on objective and self-reported insomnia variables and self-reported daytime functioning in patients with untreated mild OSA and comorbid insomnia disorder (COMISA).", "No safety concerns were reported for daridorexant 50 or 25 mg." ] }, { "citation": "Huang Z, Wang H, Zhang B, Li C, Wang J, Xu L, et al. Efficacy and safety of daridorexant in Chinese patients with insomnia disorder: a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial.. Sleep. 2025;48(12):zsaf170. doi:10.1093/sleep/zsaf170 PMID:40557879.", "doi": "10.1093/sleep/zsaf170", "languages": [ "eng" ], "pmid": "40557879", "publication_types": [ "journal article", "randomized controlled trial", "clinical trial, phase iii", "multicenter study", "research support, non-u.s. gov't" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/40557879/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "Efficacy and safety of daridorexant in Chinese patients with insomnia disorder: a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial.", "STUDY OBJECTIVES: To evaluate the efficacy and safety of daridorexant in Chinese patients with insomnia disorder.", "CONCLUSIONS: Daridorexant 50 mg significantly improved both objective and self-reported sleep outcomes in Chinese patients with insomnia disorder, with a favorable safety profile." ] }, { "citation": "Lederer K, Benes H, Fine A, Shoffner S, Bacchelli S, Diaz DC, et al. A randomised crossover trial of daridorexant for the treatment of chronic insomnia and nocturia.. Journal of sleep research. 2025;34(6):e70002. doi:10.1111/jsr.70002 PMID:40083090.", "doi": "10.1111/jsr.70002", "languages": [ "eng" ], "pmid": "40083090", "publication_types": [ "journal article", "randomized controlled trial", "research support, non-u.s. gov't" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/40083090/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "This double-blind, placebo-controlled, two-way crossover trial evaluated the efficacy and safety of daridorexant in patients with chronic insomnia and comorbid nocturia.", "No adverse events of special interest (falls/urinary incontinence) were reported during daridorexant treatment.", "In conclusion, in patients with chronic insomnia and nocturia, daridorexant improves both conditions with a favourable safety profile." ] }, { "citation": "Sun Y, Xu T, Xu H. Safety of dual orexin receptor antagonists: a real-world pharmacovigilance study.. Expert opinion on drug safety. 2026;25(9):1695-1701. doi:10.1080/14740338.2025.2471520 PMID:39985333.", "doi": "10.1080/14740338.2025.2471520", "languages": [ "eng" ], "pmid": "39985333", "publication_types": [ "journal article" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39985333/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "METHODS: Data related to daridorexant, suvorexant, and lemborexant were collected from the US Food and Drug Administration Adverse Event Reporting System between the first quarter of 2022 and the third quarter of 2024.", "The highest signal of strength of PT was sleep paralysis for daridorexant and lemborexant, and abnormal sleep-related event for suvorexant.", "The most frequent PT was somnolence for lemborexant (30, 11.54%) and insomnia for daridorexant (252, 14.50%) and suvorexant (62, 9.30%) within the top 30 PTs." ] }, { "citation": "Magliocca M, Koopmans I, Vaillant C, Lemoine V, Zuiker R, Dingemanse J, et al. Nighttime safety of daridorexant: Evaluation of responsiveness to an external noise stimulus, postural stability, walking, and cognitive function.. Journal of psychopharmacology (Oxford, England). 2025;39(3):223-232. doi:10.1093/sleep/zsx086 PMID:39641404.", "doi": "10.1093/sleep/zsx086", "languages": [ "eng" ], "pmid": "39641404", "publication_types": [ "journal article", "randomized controlled trial" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39641404/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "Nighttime safety of daridorexant: Evaluation of responsiveness to an external noise stimulus, postural stability, walking, and cognitive function." ] }, { "citation": "Jiang M, Li H, Kong L. Data mining and safety analysis of dual orexin receptor antagonists (DORAs): a real-world pharmacovigilance study based on the FAERS database.. Frontiers in pharmacology. 2024;15:1436405. doi:10.3389/fphar.2021.766125 PMID:39166117.", "doi": "10.3389/fphar.2021.766125", "languages": [ "eng" ], "pmid": "39166117", "publication_types": [ "journal article" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39166117/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "RESULTS: A total of 11,857 DORAs-related adverse reactions were detected, reported with suvorexant, lemborexant, and daridorexant as the main suspected drugs was 8717584, and 2556, respectively." ] }, { "citation": "Uchimura N, Ozone M, Suzuki M, Taniguchi M, Kuriyama K, Togo O, et al. Long-term safety and efficacy of daridorexant in Japanese patients with insomnia disorder.. Sleep medicine. 2024;122:64-70. doi:10.1016/j.sleep.2024.07.036 PMID:39128336.", "doi": "10.1016/j.sleep.2024.07.036", "languages": [ "eng" ], "pmid": "39128336", "publication_types": [ "journal article", "randomized controlled trial", "clinical trial, phase iii", "multicenter study", "research support, non-u.s. gov't" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39128336/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "Long-term safety and efficacy of daridorexant in Japanese patients with insomnia disorder.", "OBJECTIVE/BACKGROUND: The short-term efficacy and safety of daridorexant, a dual orexin receptor antagonist, has been demonstrated in Japanese patients with insomnia disorder.", "The objective of this study was to evaluate, in a non-overlapping patient population to the short-term study, the long-term safety and efficacy of daridorexant in Japanese patients with insomnia disorder." ] }, { "citation": "Uchiyama M, Mishima K, Yagi T, Yoshihara T, Eto T, Muehlan C, et al. Pharmacokinetics, safety, and efficacy of daridorexant in Japanese subjects: Results from phase 1 and 2 studies.. Journal of sleep research. 2025;34(1):e14302. doi:10.1111/jsr.14302 PMID:39118245.", "doi": "10.1111/jsr.14302", "languages": [ "eng" ], "pmid": "39118245", "publication_types": [ "clinical trial, phase i", "clinical trial, phase ii", "journal article", "randomized controlled trial", "research support, non-u.s. gov't" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39118245/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "Pharmacokinetics, safety, and efficacy of daridorexant in Japanese subjects: Results from phase 1 and 2 studies." ] }, { "citation": "Uchimura N, Taniguchi M, Ariyoshi Y, Oka Y, Togo O, Uchiyama M. Daridorexant in Japanese patients with insomnia disorder: A phase 3, randomized, double-blind, placebo-controlled study.. Sleep medicine. 2024;122:27-34. doi:10.1016/j.sleep.2024.07.037 PMID:39116704.", "doi": "10.1016/j.sleep.2024.07.037", "languages": [ "eng" ], "pmid": "39116704", "publication_types": [ "journal article", "randomized controlled trial", "clinical trial, phase iii", "multicenter study", "research support, non-u.s. gov't" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39116704/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "OBJECTIVE: This Phase 3 double-blind, placebo-controlled study evaluated the efficacy and safety of daridorexant in Japanese patients with insomnia disorder.", "PATIENTS/METHODS: 490 patients with insomnia disorder from 95 sites in Japan were randomized to daridorexant 50 mg (n = 163), 25 mg (n = 163) or placebo (n = 164) for 4 weeks, followed by a 7-day placebo run-out and a 30-day safety follow-up." ] }, { "citation": "Wang Q, Zhou Q, Du Z, Lu R, Jiang Y, Zhu H. Clinical safety of daridorexant in insomnia treatment: Analysis of FDA adverse event reports.. Journal of affective disorders. 2024;362:552-559. doi:10.1016/j.jad.2024.07.034 PMID:39019232.", "doi": "10.1016/j.jad.2024.07.034", "languages": [ "eng" ], "pmid": "39019232", "publication_types": [ "journal article" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/39019232/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "Clinical safety of daridorexant in insomnia treatment: Analysis of FDA adverse event reports.", "The aim of this study is to delve into the adverse events (AEs) of daridorexant by analyzing data from the FAERS database, to assess its safety and effectiveness in clinical applications.", "Signal mining identified new potential AEs related to daridorexant, including sleep-related psychiatric symptoms (nightmare, abnormal dreams, sleep terror, etc.), emotional and perceptual abnormalities (hallucination, depression, agitation), physiological and behavioral responses (palpitations, dry mouth, energy increased, etc.), suicide risk (suicidal ideation, intentional overdose), and other special concern AEs (tachyphrenia, sleep-related eating disorder, hypersensitivity)." ] }, { "citation": "Chalet FX, Luyet PP, Rabasa C, Vaillant C, Saskin P, Ahuja A, et al. Daridorexant for patients with chronic insomnia disorder: number needed to treat, number needed to harm, and likelihood to be helped or harmed.. Postgraduate medicine. 2024;136(4):396-405. doi:10.1080/00325481.2024.2359891 PMID:38814132.", "doi": "10.1080/00325481.2024.2359891", "languages": [ "eng" ], "pmid": "38814132", "publication_types": [ "journal article", "randomized controlled trial", "clinical trial, phase iii" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/38814132/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "Daridorexant for patients with chronic insomnia disorder: number needed to treat, number needed to harm, and likelihood to be helped or harmed.", "OBJECTIVES: Appraise the evidence for daridorexant 50 mg and 25 mg versus placebo when treating chronic insomnia disorder in terms of number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).", "All LHH ratios at Months 1 and 3 were >1 (except for daridorexant 25 mg for the IDSIQ alert/cognition domain), indicating that patients were more likely to respond to daridorexant 50 mg and 25 mg than to experience an AE of somnolence, headache, or fatigue." ] }, { "citation": "McIntyre RS, Wong S, Kwan ATH, Rhee TG, Teopiz KM, Ho R, et al. Association between dual orexin receptor antagonists (DORAs) and suicidality: reports to the United States Food and Drug Administration Adverse Event Reporting System (FAERS).. Expert opinion on drug safety. 2025;24(6):753-757. doi:10.1080/14740338.2024.2361300 PMID:38804896.", "doi": "10.1080/14740338.2024.2361300", "languages": [ "eng" ], "pmid": "38804896", "publication_types": [ "journal article", "comparative study" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/38804896/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "BACKGROUND: Package inserts for the FDA-approved dual orexin receptor antagonists (DORAs) suvorexant, lemborexant and daridorexant state that suicide risk should be monitored." ] }, { "citation": "Di Marco T, Djonlagic I, Dauvilliers Y, Sadeghi K, Little D, Datta AN, et al. Effect of daridorexant on sleep architecture in patients with chronic insomnia disorder: a pooled post hoc analysis of two randomized phase 3 clinical studies.. Sleep. 2024;47(11):zsae098. doi:10.1016/j.ijpsycho.2021.07.626 PMID:38644625.", "doi": "10.1016/j.ijpsycho.2021.07.626", "languages": [ "eng" ], "pmid": "38644625", "publication_types": [ "journal article", "randomized controlled trial", "clinical trial, phase iii", "research support, non-u.s. gov't" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/38644625/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "CLINICAL TRIALS: ClinicalTrials.gov NCT03545191: study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants with insomnia disorder.", "URL: Study Details | study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants with insomnia disorder | ClinicalTrials.gov ClinicalTrials.gov NCT03575104:study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants who experience difficulties sleeping.", "URL: study details | study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants who experience difficulties sleeping | ClinicalTrials.gov." ] }, { "citation": "Álamo C, Sáiz Ruiz J, Zaragozá Arnáez C. Orexinergic Receptor Antagonists as a New Therapeutic Target to Overcome Limitations of Current Pharmacological Treatment of Insomnia Disorder.. Actas espanolas de psiquiatria. 2024;52(2):172-182. doi:10.62641/aep.v52i2.1659 PMID:38622003.", "doi": "10.62641/aep.v52i2.1659", "languages": [ "eng" ], "pmid": "38622003", "publication_types": [ "journal article" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/38622003/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "Dual orexin receptor antagonists (DORAs) such as daridorexant, lemborexant, and suvorexant, represent a novel approach to insomnia treatment by inhibiting wakefulness rather than enhancing sedation.", "As the only DORA approved for insomnia treatment by the European Medicines Agency (EMA) and Food and Drug Administration (FDA), daridorexant has demonstrated sustained efficacy over a 12-month period, improving nocturnal sleep parameters and daytime functionality, with a favorable safety and tolerability profile." ] }, { "citation": "Cicala G, Barbieri MA, Russo G, Salvo F, Spina E. Safety of Dual Orexin Receptor Antagonist Daridorexant: A Disproportionality Analysis of Publicly Available FAERS Data.. Pharmaceuticals (Basel, Switzerland). 2024;17(3):342. doi:10.1007/s40801-021-00278-z PMID:38543128.", "doi": "10.1007/s40801-021-00278-z", "languages": [ "eng" ], "pmid": "38543128", "publication_types": [ "journal article" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/38543128/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "Safety of Dual Orexin Receptor Antagonist Daridorexant: A Disproportionality Analysis of Publicly Available FAERS Data.", "These data provide valuable insights into the real-world safety profile of daridorexant, supporting the existence of safety signals related to nightmares, depression, and hangovers." ] }, { "citation": "Fernandes M, Placidi F, Mercuri NB, Liguori C. Daridorexant treatment for chronic insomnia: a real-world retrospective single-center study.. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2024;45(7):3443-3448. doi:10.1016/j.smrv.2020.101332 PMID:38280086.", "doi": "10.1016/j.smrv.2020.101332", "languages": [ "eng" ], "pmid": "38280086", "publication_types": [ "journal article", "observational study" ], "pubmed_url": "https://pubmed.ncbi.nlm.nih.gov/38280086/", "why_flagged": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "why_flagged_detail": [ "This retrospective observational study aimed to describe real-world data on daridorexant effectiveness and safety in adult patients with CID.", "CONCLUSIONS: This study suggests daridorexant to be effective and safe in real-world CID treatment whether used as a first-ever treatment, switch, or add-on, as reflected by subjective and objective measures and the absence of serious treatment-related adverse events." ] } ], "protocol": { "decision_rule_order": [ "X1", "X2", "X3", "X4", "X5", "INCLUDE" ], "dual_screening_note": "This record is a single-pass demonstration run. Production delivery applies dual independent screening with adjudication; the protocol above is the published version of the rule set used here.", "exclusion_criteria": [ "X1 NOT_HUMAN — in vitro, animal or other non-clinical evidence only.", "X2 NO_NEW_CASES — review, editorial, comment, guideline or meta-analysis carrying no new case data.", "X3 NO_SAFETY_DATA — the record reports no adverse event, tolerability or safety outcome.", "X4 DRUG_NOT_IMPLICATED — the medicine is mentioned but no reported adverse event is attributed to it.", "X5 RECORD_INCOMPLETE — citation data insufficient to screen; routed to manual review, never silently dropped." ], "inclusion_criteria": [ "I1 HUMAN — the record reports exposure in humans (clinical trial, observational study, case report, case series, real-world evidence or spontaneous report).", "I2 IMPLICATED — the medicine is implicated in a reported adverse event, tolerability finding or safety outcome.", "I3 RETRIEVABLE — full citation data (PMID, title, journal, year, authors, abstract) was retrieved, so the decision is auditable." ], "protocol_document": "screening_protocol.md", "protocol_id": "ZIIX-PV-LS-001", "protocol_version": "1.0", "reason_codes": { "INCLUDE": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "X1": "X1 — NOT_HUMAN: no human exposure; in vitro, animal or other non-clinical evidence only.", "X2": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "X3": "X3 — NO_SAFETY_DATA: the record reports no adverse event, tolerability or safety outcome.", "X4": "X4 — DRUG_NOT_IMPLICATED: the medicine is mentioned, but no reported adverse event is attributed to it.", "X5": "X5 — RECORD_INCOMPLETE: citation data insufficient to screen; routed to manual review, never silently dropped.", "X6": "X6 — STUDY_PROTOCOL: a study protocol or design paper reporting no results; it can contain no case." }, "title": "Medical literature screening protocol — single-medicine PubMed/MEDLINE run" }, "records": [ { "citation": "Sun D, Li J, Chen G, Liu X, Jiang C, Ye T. Suicidal ideation associated with daridorexant treatment in insomnia patients: Comparator-restricted disproportionality analysis and assessment of potential heterogeneity in reporting patterns.. Social psychiatry and psychiatric epidemiology. 2026:10.1007/s00127-026-03227-9. doi:10.1016/j.jclinepi.2023.08.010 PMID:42888253.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "patients", "receptor" ], "implication_evidence": [ "Suicidal ideation associated with daridorexant treatment in insomnia patients: Comparator-restricted disproportionality analysis and assessment of potential heterogeneity in reporting patterns.", "Although previous studies have identified a significant signal for suicidal ideation associated with daridorexant when compared with all other drugs, the significance when compared specifically with insomnia medications and the potential differences in reporting patterns of suicidal ideation across subgroups remain unclear.", "Additionally, there may be potential differences in reporting patterns of daridorexant-associated suicidal ideation across subgroups." ], "safety_vocabulary_found": [ "adverse", "event", "events", "suicidal" ] }, "pmid": "42888253", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Saliba R, Cercone J, El-Solh AA. Current perspectives on the pharmacotherapeutic management of insomnia in Veterans.. Expert opinion on pharmacotherapy. 2026:1-13. doi:10.1080/14656566.2026.2749647 PMID:42873187.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "patients", "receptor" ], "publication_types": [ "journal article", "review" ] }, "pmid": "42873187", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Saladi S, Jouda H, Yong T, Anderson KN. Long-term outcomes of daridorexant in those with comorbid insomnia.. BJPsych bulletin. 2026:1-6. doi:10.1192/bjb.2026.10298 PMID:42864752.", "decision": "EXCLUDE", "evidence": { "reason_detail": "the medicine appears only as background; no reported adverse event is attributed to it in any sentence", "safety_vocabulary_found": [ "adverse", "events", "suicidality" ] }, "pmid": "42864752", "reason": "X4 — DRUG_NOT_IMPLICATED: the medicine is mentioned, but no reported adverse event is attributed to it.", "reason_code": "X4" }, { "citation": "Shalihin MSE, Abdul Aziz MAN, Sharin SI. Pharmacological and non-pharmacological interventions of insomnia in geriatrics: A systematic review.. The Medical journal of Malaysia. 2026;81(5):787-794 PMID:42813493.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "receptor", "trial" ], "publication_types": [ "journal article", "meta-analysis", "systematic review" ] }, "pmid": "42813493", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Svedmyr S, Bergqvist J. Daridorexant- Case Report of Possible Side-Effect in Rare Mitochondrial Disorder.. Journal of sleep research. 2026:e70440. doi:10.1111/jsr.70440 PMID:42674807.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "case report", "patients" ], "implication_evidence": [ "Daridorexant- Case Report of Possible Side-Effect in Rare Mitochondrial Disorder." ], "safety_vocabulary_found": [ "side-effect", "symptoms" ] }, "pmid": "42674807", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Araujo LMM, Sousa AD, Vieira CC, Abreu JPP, Conti CF, Silva MML, et al. Long-term use of dual orexin receptor antagonists for the treatment of insomnia: a systematic review and meta-analysis.. Arquivos de neuro-psiquiatria. 2026;84(7):1-10. doi:10.1007/s40265-022-01699-y PMID:42595319.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "discontinuation", "participants", "patient", "patient-reported", "receptor", "trial" ], "publication_types": [ "journal article", "meta-analysis", "systematic review" ] }, "pmid": "42595319", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Wang X, Wang Y, Wang M, Zheng Q, Li M, Zheng Y, et al. The \"efficacy window\" phenomenon of daridorexant in insomnia treatment: a dose-dependent time-course meta-analysis.. Frontiers in pharmacology. 2026;17:1847130. doi:10.1212/WNL.0000000000009475 PMID:42453571.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "patients" ], "publication_types": [ "journal article", "systematic review" ] }, "pmid": "42453571", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "He S, Zeng J, Zhang Y, Ruan X. Dual orexin receptor antagonists for preventing delirium in hospitalized older adults: protocol for a randomized-trial systematic review and meta-analysis.. Systematic reviews. 2026;15(1):261. doi:10.1136/bmj.39489.470347.AD PMID:42437946.", "decision": "EXCLUDE", "evidence": { "matched_terms": [ "protocol for a" ], "reason_detail": "the title identifies a study protocol or design paper, which reports no results" }, "pmid": "42437946", "reason": "X6 — STUDY_PROTOCOL: a study protocol or design paper reporting no results; it can contain no case.", "reason_code": "X6" }, { "citation": "O'Regan D. Real-world experience with daridorexant for insomnia in adults with intellectual disabilities: a retrospective single-centre case series.. Drugs in context. 2026;15:2026-5-4. doi:10.1111/jsr.14399 PMID:42422713.", "decision": "EXCLUDE", "evidence": { "publication_types": [ "journal article" ], "safety_vocabulary_found": [] }, "pmid": "42422713", "reason": "X3 — NO_SAFETY_DATA: the record reports no adverse event, tolerability or safety outcome.", "reason_code": "X3" }, { "citation": "Qi L, Liu J, Wang K, Li Q. Mechanistic insights into the safety of daridorexant in older adults: From postural stability to next-day function.. Journal of psychopharmacology (Oxford, England). 2026;40(10):1680-1682. doi:10.1177/02698811261453852 PMID:42206495.", "decision": "EXCLUDE", "evidence": { "human_evidence": [], "publication_types": [ "letter" ] }, "pmid": "42206495", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Fietze I, Boof ML, Lederer K, Lemoine V, Vaillant C, Pépin JL. Daridorexant in severe obstructive sleep apnea: effects on sleep-disordered breathing and sleep.. Sleep. 2026;49(9):zsag145. doi:10.5664/jcsm.9300 PMID:42171662.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "participants", "patients", "receptor", "trial" ], "implication_evidence": [ "Four adverse events were reported (daridorexant n = 3;" ], "safety_vocabulary_found": [ "adverse", "events", "safety", "symptoms", "well-tolerated" ] }, "pmid": "42171662", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Rollo E, Antonioni A, Manzoli L, Di Lorenzo F, Flacco ME. Treatment of chronic insomnia in elderly adults with dual orexin receptor antagonists: a systematic review and meta-analysis.. Sleep. 2026;49(8):zsag135. doi:10.1038/s44323-025-00025-5 PMID:42143581.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "patients", "receptor" ], "publication_types": [ "journal article", "meta-analysis", "systematic review" ] }, "pmid": "42143581", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Terauchi M. Sleep Disturbances during Menopause: Mechanisms and Management Approaches.. Journal of menopausal medicine. 2026;32(1):12-17. doi:10.6118/jmm.25111 PMID:42045086.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "cohort", "patient", "receptor" ], "publication_types": [ "journal article", "review" ] }, "pmid": "42045086", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Coloma P, Coury D, Wernette S, Beevers V, Dubois C, Di Marco T, et al. Daridorexant in children and adolescents with insomnia disorder: study protocol for a multicentre randomised controlled trial.. BMJ open. 2026;16(4):e099888. doi:10.5664/jcsm.7228 PMID:41942161.", "decision": "EXCLUDE", "evidence": { "matched_terms": [ "protocol for a", "study protocol" ], "reason_detail": "the title identifies a study protocol or design paper, which reports no results" }, "pmid": "41942161", "reason": "X6 — STUDY_PROTOCOL: a study protocol or design paper reporting no results; it can contain no case.", "reason_code": "X6" }, { "citation": "Winter Y, Arnaldi D. Daridorexant: exploring its role in the treatment of insomnia disorder.. Expert review of neurotherapeutics. 2026;26(4):325-340. doi:10.1080/14737175.2026.2639557 PMID:41817674.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "patient", "patient-reported", "patients", "receptor" ], "publication_types": [ "journal article", "review" ] }, "pmid": "41817674", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Hoxhaj D, Colitta A, Maestri Tassoni M, Pascazio A, Buracchi Torresi F, Turco F, et al. Real-world findings of daridorexant in chronic insomnia: A pilot study on subjective and actigraphic sleep parameters.. Sleep medicine. 2026;142:108839. doi:10.1016/j.sleep.2026.108839 PMID:41719767.", "decision": "EXCLUDE", "evidence": { "reason_detail": "the medicine appears only as background; no reported adverse event is attributed to it in any sentence", "safety_vocabulary_found": [ "adverse", "event", "sleep paralysis", "symptoms" ] }, "pmid": "41719767", "reason": "X4 — DRUG_NOT_IMPLICATED: the medicine is mentioned, but no reported adverse event is attributed to it.", "reason_code": "X4" }, { "citation": "von Fabeck K, Boudsocq JP, Boye M, French PCC Research Group, Simon N. Clinical toxicity of daridorexant: a retrospective analysis of poison centre data.. Clinical toxicology (Philadelphia, Pa.). 2026;64(6):497-502. doi:10.1080/15563650.2026.2617481 PMID:41700897.", "decision": "EXCLUDE", "evidence": { "reason_detail": "the medicine appears only as background; no reported adverse event is attributed to it in any sentence", "safety_vocabulary_found": [ "adverse", "hallucinations", "overdose", "risk", "safety", "safety profile" ] }, "pmid": "41700897", "reason": "X4 — DRUG_NOT_IMPLICATED: the medicine is mentioned, but no reported adverse event is attributed to it.", "reason_code": "X4" }, { "citation": "Kishi T, Ikuta T, Sakuma K, Hatano M, Kishi T, Kitajima T, et al. Comparative effects of hypnotic agents on sleep architecture and respiratory outcomes in obstructive sleep apnea: A systematic review and network meta-analysis.. Psychiatry and clinical neurosciences. 2026;80(5):390-397. doi:10.1111/pcn.70036 PMID:41665171.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "discontinuation" ], "publication_types": [ "comparative study", "journal article", "network meta-analysis", "systematic review" ] }, "pmid": "41665171", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Schaedel Z, Bakker TR, Bassetti C, Briasoulis O, Cassel P, Pain S, et al. 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;206:108821. doi:10.1016/j.maturitas.2025.108821 PMID:41506007.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "patients", "subjects", "trial" ], "implication_evidence": [ "Efficacy and safety of daridorexant for the treatment of insomnia disorder in women of menopausal transition age: Insights from a randomized controlled trial.", "OBJECTIVES: To evaluate the efficacy and safety of daridorexant in women aged 47-55 years with insomnia disorder, an age group representative of the menopause transition.", "Daridorexant 50 mg is well tolerated in this population, with no increased risk of next-morning sleepiness or somnolence." ], "safety_vocabulary_found": [ "adverse", "events", "risk", "safety", "somnolence", "symptoms" ] }, "pmid": "41506007", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Young B, Zhuang T, Fernando N, Manner P, Kamal RN, Hernandez NM. Evaluating the Safety of Prescription Sleep Medications in Patients Undergoing Total Knee Arthroplasty: A Propensity Matched Analysis.. The Journal of the American Academy of Orthopaedic Surgeons. 2026;34(19):e2719-e2726. doi:10.5435/JAAOS-D-25-00888 PMID:41490393.", "decision": "EXCLUDE", "evidence": { "reason_detail": "the medicine appears only as background; no reported adverse event is attributed to it in any sentence", "safety_vocabulary_found": [ "risk", "safety" ] }, "pmid": "41490393", "reason": "X4 — DRUG_NOT_IMPLICATED: the medicine is mentioned, but no reported adverse event is attributed to it.", "reason_code": "X4" }, { "citation": "Chino Y, Sugiyama H, Chaki S, Sato Y. Current and novel dual orexin receptor antagonists for the treatment of insomnia: the emergence of vornorexant.. The international journal of neuropsychopharmacology. 2025;28(12):pyaf077. doi:10.5664/jcsm.7036 PMID:41273062.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "humans", "patients", "receptor" ], "publication_types": [ "journal article", "research support, non-u.s. gov't", "review" ] }, "pmid": "41273062", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Kono S, Nishiyama T, Nakano S, Ishimoto Y, Horikoshi S. Real-World Effectiveness and Safety of Daridorexant in Japanese Patients With Insomnia: A Multicenter Observational Study Evaluating Four-Week Changes in Athens Insomnia Scale Among 54 Participants.. Cureus. 2025;17(11):e97174. doi:10.7759/cureus.97174 PMID:41262489.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "participants", "patients", "real-world", "receptor" ], "implication_evidence": [ "Real-World Effectiveness and Safety of Daridorexant in Japanese Patients With Insomnia: A Multicenter Observational Study Evaluating Four-Week Changes in Athens Insomnia Scale Among 54 Participants.", "Therefore, this observational study assessed the effectiveness and safety of daridorexant in real-world settings for Japanese participants with insomnia beyond those evaluated in previous clinical trials." ], "safety_vocabulary_found": [ "adverse", "aes", "events", "risk", "safety", "safety profile", "symptoms" ] }, "pmid": "41262489", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Pathmanathan J, Little D, Sadeghi K, Di Marco T, Kleinschmidt D, Nerrie J, et al. The Insomnia EEG Score: a new tool for the classification of people with poor sleep.. Sleep. 2026;49(4):zsaf353. doi:10.1093/sleep/zsaf353 PMID:41217192.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "cohort", "subjects" ], "implication_evidence": [ "Clinical Trials Study to Assess the Efficacy and Safety of ACT-541468 (Daridorexant) in Adult and Elderly Subjects with Insomnia Disorder, https://clinicaltrials.gov/study/NCT03545191, NCT03545191;", "Study to Assess the Efficacy and Safety of ACT-541468 (Daridorexant) in Adult and Elderly Subjects Suffering from Difficulties to Sleep, https://www.clinicaltrials.gov/study/NCT03575104, NCT03575104." ], "safety_vocabulary_found": [ "safety" ] }, "pmid": "41217192", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Vasudeva S, Wong S, Le GH, Dri CE, Teopiz KM, Ho R, et al. Efficacy and safety profiles of FDA-approved dual orexin receptor antagonists in depression: A systematic review of pre-clinical and clinical studies.. Journal of psychiatric research. 2025;191:752-769. doi:10.1016/j.jpsychires.2025.10.001 PMID:41109037.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "healthy", "receptor" ], "publication_types": [ "journal article", "research support, n.i.h., extramural", "systematic review" ] }, "pmid": "41109037", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Liu H, Wang Y, Li M, Liu X, Chen X, Zhu B, et al. Efficacy and safety of insomnia pharmacotherapies: Convergent evidence from Bayesian network meta-regression and FAERS-based disproportionality analysis.. Sleep medicine. 2025;136:106848. doi:10.1016/j.sleep.2025.106848 PMID:41101148.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "patients", "pharmacovigilance", "receptor" ], "publication_types": [ "journal article", "network meta-analysis", "research support, non-u.s. gov't", "review" ] }, "pmid": "41101148", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Żełabowski K, Petrov W, Wojtysiak K, Ratka Z, Biedka K, Wesołowski M, et al. Targeting the Orexin System in the Pharmacological Management of Insomnia and Other Diseases: Suvorexant, Lemborexant, Daridorexant, and Novel Experimental Agents.. International journal of molecular sciences. 2025;26(17):8700. doi:10.1093/sleep/zsab072.057 PMID:40943625.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "receptor", "receptors" ], "publication_types": [ "journal article", "review" ] }, "pmid": "40943625", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Ferini-Strambi L, Arnaldi D, Bonanni E, Cicolin A, Gigli GL, Liguori C, et al. Daridorexant and Insomnia in Clinical Practice: A Nominal Group Technique Consensus Study among Italian Sleep and Insomnia Experts.. Current neuropharmacology. 2026;24(1):135-149. doi:10.1016/j.smrv.2023.101762 PMID:40776640.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "patient", "receptor" ], "implication_evidence": [ "Key findings highlight daridorexant's mechanism of action, safety profile, efficacy on night and day parameters, and suitability for long-term use.", "DISCUSSION: Daridorexant may address insomnia without increasing sedation via its dual orexin receptor antagonism." ], "safety_vocabulary_found": [ "safety", "safety profile", "sedation" ] }, "pmid": "40776640", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Lettieri CJ, Briasoulis O, Léger D, Luyet PP, Pépin JL, Quan SF, et al. 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.. Journal of sleep research. 2026;35(2):e70135. doi:10.5664/jcsm.7112 PMID:40660750.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "participants", "patients", "receptor", "trial" ], "implication_evidence": [ "This post hoc analysis evaluated the efficacy and safety of daridorexant 25 and 50 mg on objective and self-reported insomnia variables and self-reported daytime functioning in patients with untreated mild OSA and comorbid insomnia disorder (COMISA).", "No safety concerns were reported for daridorexant 50 or 25 mg." ], "safety_vocabulary_found": [ "adverse", "events", "safety", "somnolence", "symptoms" ] }, "pmid": "40660750", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Sena C, Albuquerque P, Oliveira J, Vieira D. Molecular Insights into the Interaction of Orexin 1 Receptor Antagonists: A Comprehensive Study Using Classical and Quantum Computational Methods.. Molecules (Basel, Switzerland). 2025;30(13):2790. doi:10.1002/jcc.10189 PMID:40649305.", "decision": "EXCLUDE", "evidence": { "reason_detail": "the medicine appears only as background; no reported adverse event is attributed to it in any sentence", "safety_vocabulary_found": [ "dependence", "safety" ] }, "pmid": "40649305", "reason": "X4 — DRUG_NOT_IMPLICATED: the medicine is mentioned, but no reported adverse event is attributed to it.", "reason_code": "X4" }, { "citation": "Fang J, Wang Y, He J, Ge C, Zhang Y, Liu Y, et al. Discovery, asymmetric synthesis and biological evaluation of new bisbenzylisoquinoline-orexin receptor antagonists for insomnia treatment.. European journal of medicinal chemistry. 2025;297:117957. doi:10.1016/j.ejmech.2025.117957 PMID:40644919.", "decision": "EXCLUDE", "evidence": { "reason_detail": "the medicine appears only as background; no reported adverse event is attributed to it in any sentence", "safety_vocabulary_found": [ "safety", "toxicity" ] }, "pmid": "40644919", "reason": "X4 — DRUG_NOT_IMPLICATED: the medicine is mentioned, but no reported adverse event is attributed to it.", "reason_code": "X4" }, { "citation": "Huang Z, Wang H, Zhang B, Li C, Wang J, Xu L, et al. Efficacy and safety of daridorexant in Chinese patients with insomnia disorder: a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial.. Sleep. 2025;48(12):zsaf170. doi:10.1093/sleep/zsaf170 PMID:40557879.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "participants", "patients", "trial" ], "implication_evidence": [ "Efficacy and safety of daridorexant in Chinese patients with insomnia disorder: a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial.", "STUDY OBJECTIVES: To evaluate the efficacy and safety of daridorexant in Chinese patients with insomnia disorder.", "CONCLUSIONS: Daridorexant 50 mg significantly improved both objective and self-reported sleep outcomes in Chinese patients with insomnia disorder, with a favorable safety profile." ], "safety_vocabulary_found": [ "adverse", "aes", "events", "next-day", "safety", "safety profile", "symptoms", "withdrawal" ] }, "pmid": "40557879", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Kishi T, Ikuta T, Citrome L, Sakuma K, Hatano M, Hamanaka S, et al. Comparative efficacy and safety of daridorexant, lemborexant, and suvorexant for insomnia: a systematic review and network meta-analysis.. Translational psychiatry. 2025;15(1):211. doi:10.1111/jsr.14302 PMID:40555730.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "discontinuation", "receptor" ], "publication_types": [ "comparative study", "journal article", "network meta-analysis", "systematic review" ] }, "pmid": "40555730", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Briggs AH, Chalet FX, Cooper J, Graham P, Palmer S, Miller P, et al. Cost-Effectiveness Analysis of Daridorexant for the Pharmacological Treatment of Chronic Insomnia Disorder in Adults.. PharmacoEconomics - open. 2025;9(3):379-397. doi:10.1093/intqhc/mzq068 PMID:40153194.", "decision": "EXCLUDE", "evidence": { "reason_detail": "the medicine appears only as background; no reported adverse event is attributed to it in any sentence", "safety_vocabulary_found": [ "adverse", "events" ] }, "pmid": "40153194", "reason": "X4 — DRUG_NOT_IMPLICATED: the medicine is mentioned, but no reported adverse event is attributed to it.", "reason_code": "X4" }, { "citation": "Di Nicola M, Pepe M, Bonomo L, Milintenda M, Panaccione I, Brugnoli R, et al. A Preliminary Report on the Effects of Daridorexant in Patients with Comorbid Insomnia and Substance Use Disorders.. Pharmaceuticals (Basel, Switzerland). 2025;18(3):378. doi:10.1159/000514965 PMID:40143154.", "decision": "EXCLUDE", "evidence": { "reason_detail": "the medicine appears only as background; no reported adverse event is attributed to it in any sentence", "safety_vocabulary_found": [ "safety", "symptoms", "tolerability" ] }, "pmid": "40143154", "reason": "X4 — DRUG_NOT_IMPLICATED: the medicine is mentioned, but no reported adverse event is attributed to it.", "reason_code": "X4" }, { "citation": "Tang M, Shen Z, Yu P, Yu M, Tong X, Jiang G. Comparison of efficacy and safety of dual orexin receptor antagonists lemborexant and daridorexant for the treatment of insomnia: a systematic review and meta-analysis.. Psychopharmacology. 2025;242(8):1693-1711. doi:10.1007/s00213-025-06773-3 PMID:40133470.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "patient", "patients", "receptor" ], "publication_types": [ "comparative study", "journal article", "meta-analysis", "systematic review" ] }, "pmid": "40133470", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Lederer K, Benes H, Fine A, Shoffner S, Bacchelli S, Diaz DC, et al. A randomised crossover trial of daridorexant for the treatment of chronic insomnia and nocturia.. Journal of sleep research. 2025;34(6):e70002. doi:10.1111/jsr.70002 PMID:40083090.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "patients", "trial" ], "implication_evidence": [ "This double-blind, placebo-controlled, two-way crossover trial evaluated the efficacy and safety of daridorexant in patients with chronic insomnia and comorbid nocturia.", "No adverse events of special interest (falls/urinary incontinence) were reported during daridorexant treatment.", "In conclusion, in patients with chronic insomnia and nocturia, daridorexant improves both conditions with a favourable safety profile." ], "safety_vocabulary_found": [ "adverse", "complaints", "events", "safety", "safety profile", "symptoms" ] }, "pmid": "40083090", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Sun Y, Xu T, Xu H. Safety of dual orexin receptor antagonists: a real-world pharmacovigilance study.. Expert opinion on drug safety. 2026;25(9):1695-1701. doi:10.1080/14740338.2025.2471520 PMID:39985333.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "pharmacovigilance", "real-world", "receptor" ], "implication_evidence": [ "METHODS: Data related to daridorexant, suvorexant, and lemborexant were collected from the US Food and Drug Administration Adverse Event Reporting System between the first quarter of 2022 and the third quarter of 2024.", "The highest signal of strength of PT was sleep paralysis for daridorexant and lemborexant, and abnormal sleep-related event for suvorexant.", "The most frequent PT was somnolence for lemborexant (30, 11.54%) and insomnia for daridorexant (252, 14.50%) and suvorexant (62, 9.30%) within the top 30 PTs." ], "safety_vocabulary_found": [ "adverse", "aes", "event", "events", "safety", "sleep paralysis", "somnolence" ] }, "pmid": "39985333", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Magliocca M, Koopmans I, Vaillant C, Lemoine V, Zuiker R, Dingemanse J, et al. Nighttime safety of daridorexant: Evaluation of responsiveness to an external noise stimulus, postural stability, walking, and cognitive function.. Journal of psychopharmacology (Oxford, England). 2025;39(3):223-232. doi:10.1093/sleep/zsx086 PMID:39641404.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "healthy", "receptor", "subjects" ], "implication_evidence": [ "Nighttime safety of daridorexant: Evaluation of responsiveness to an external noise stimulus, postural stability, walking, and cognitive function." ], "safety_vocabulary_found": [ "safety" ] }, "pmid": "39641404", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Yeh WC, Li YS, Chang YP, Hsu CY. The efficacy and safety of dual orexin receptor antagonists in obstructive sleep apnea: A systematic review and meta-analysis of randomised controlled trials.. Journal of sleep research. 2025;34(4):e14399. doi:10.1111/jsr.14399 PMID:39543812.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "patients", "receptor" ], "publication_types": [ "journal article", "meta-analysis", "systematic review" ] }, "pmid": "39543812", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Jiang M, Li H, Kong L. Data mining and safety analysis of dual orexin receptor antagonists (DORAs): a real-world pharmacovigilance study based on the FAERS database.. Frontiers in pharmacology. 2024;15:1436405. doi:10.3389/fphar.2021.766125 PMID:39166117.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "pharmacovigilance", "real-world", "receptor" ], "implication_evidence": [ "RESULTS: A total of 11,857 DORAs-related adverse reactions were detected, reported with suvorexant, lemborexant, and daridorexant as the main suspected drugs was 8717584, and 2556, respectively." ], "safety_vocabulary_found": [ "adverse", "event", "events", "hallucination", "safety", "sleep paralysis" ] }, "pmid": "39166117", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Uchimura N, Ozone M, Suzuki M, Taniguchi M, Kuriyama K, Togo O, et al. Long-term safety and efficacy of daridorexant in Japanese patients with insomnia disorder.. Sleep medicine. 2024;122:64-70. doi:10.1016/j.sleep.2024.07.036 PMID:39128336.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "patient", "patients", "receptor" ], "implication_evidence": [ "Long-term safety and efficacy of daridorexant in Japanese patients with insomnia disorder.", "OBJECTIVE/BACKGROUND: The short-term efficacy and safety of daridorexant, a dual orexin receptor antagonist, has been demonstrated in Japanese patients with insomnia disorder.", "The objective of this study was to evaluate, in a non-overlapping patient population to the short-term study, the long-term safety and efficacy of daridorexant in Japanese patients with insomnia disorder." ], "safety_vocabulary_found": [ "adverse", "events", "safety", "sleep paralysis", "symptoms", "tolerability" ] }, "pmid": "39128336", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Uchiyama M, Mishima K, Yagi T, Yoshihara T, Eto T, Muehlan C, et al. Pharmacokinetics, safety, and efficacy of daridorexant in Japanese subjects: Results from phase 1 and 2 studies.. Journal of sleep research. 2025;34(1):e14302. doi:10.1111/jsr.14302 PMID:39118245.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "exposure", "healthy", "patients", "receptor", "subjects" ], "implication_evidence": [ "Pharmacokinetics, safety, and efficacy of daridorexant in Japanese subjects: Results from phase 1 and 2 studies." ], "safety_vocabulary_found": [ "safety" ] }, "pmid": "39118245", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Uchimura N, Taniguchi M, Ariyoshi Y, Oka Y, Togo O, Uchiyama M. Daridorexant in Japanese patients with insomnia disorder: A phase 3, randomized, double-blind, placebo-controlled study.. Sleep medicine. 2024;122:27-34. doi:10.1016/j.sleep.2024.07.037 PMID:39116704.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "discontinuation", "patients" ], "implication_evidence": [ "OBJECTIVE: This Phase 3 double-blind, placebo-controlled study evaluated the efficacy and safety of daridorexant in Japanese patients with insomnia disorder.", "PATIENTS/METHODS: 490 patients with insomnia disorder from 95 sites in Japan were randomized to daridorexant 50 mg (n = 163), 25 mg (n = 163) or placebo (n = 164) for 4 weeks, followed by a 7-day placebo run-out and a 30-day safety follow-up." ], "safety_vocabulary_found": [ "adverse", "discontinuation", "event", "events", "safety", "somnolence", "symptoms", "withdrawal" ] }, "pmid": "39116704", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Luyet PP, McCall WV, Bassetti CLA, Braunstein G, Laurent J, Olivieri A, et al. Dose-response of daridorexant in insomnia disorder: An analysis of Phase 2 and 3 studies.. Sleep medicine. 2024;121:315-325. doi:10.1016/j.sleep.2024.07.019 PMID:39047305.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "patients" ], "publication_types": [ "journal article", "meta-analysis", "research support, non-u.s. gov't" ] }, "pmid": "39047305", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Wang Q, Zhou Q, Du Z, Lu R, Jiang Y, Zhu H. Clinical safety of daridorexant in insomnia treatment: Analysis of FDA adverse event reports.. Journal of affective disorders. 2024;362:552-559. doi:10.1016/j.jad.2024.07.034 PMID:39019232.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "receptor" ], "implication_evidence": [ "Clinical safety of daridorexant in insomnia treatment: Analysis of FDA adverse event reports.", "The aim of this study is to delve into the adverse events (AEs) of daridorexant by analyzing data from the FAERS database, to assess its safety and effectiveness in clinical applications.", "Signal mining identified new potential AEs related to daridorexant, including sleep-related psychiatric symptoms (nightmare, abnormal dreams, sleep terror, etc.), emotional and perceptual abnormalities (hallucination, depression, agitation), physiological and behavioral responses (palpitations, dry mouth, energy increased, etc.), suicide risk (suicidal ideation, intentional overdose), and other special concern AEs (tachyphrenia, sleep-related eating disorder, hypersensitivity)." ], "safety_vocabulary_found": [ "adverse", "ae", "aes", "event", "events", "hallucination", "overdose", "risk" ] }, "pmid": "39019232", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Chalet FX, Luyet PP, Rabasa C, Vaillant C, Saskin P, Ahuja A, et al. Daridorexant for patients with chronic insomnia disorder: number needed to treat, number needed to harm, and likelihood to be helped or harmed.. Postgraduate medicine. 2024;136(4):396-405. doi:10.1080/00325481.2024.2359891 PMID:38814132.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "participants", "patients" ], "implication_evidence": [ "Daridorexant for patients with chronic insomnia disorder: number needed to treat, number needed to harm, and likelihood to be helped or harmed.", "OBJECTIVES: Appraise the evidence for daridorexant 50 mg and 25 mg versus placebo when treating chronic insomnia disorder in terms of number needed to treat (NNT), number needed to harm (NNH), and likelihood to be helped or harmed (LHH).", "All LHH ratios at Months 1 and 3 were >1 (except for daridorexant 25 mg for the IDSIQ alert/cognition domain), indicating that patients were more likely to respond to daridorexant 50 mg and 25 mg than to experience an AE of somnolence, headache, or fatigue." ], "safety_vocabulary_found": [ "adverse", "ae", "aes", "events", "harm", "risk", "safety", "somnolence" ] }, "pmid": "38814132", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "McIntyre RS, Wong S, Kwan ATH, Rhee TG, Teopiz KM, Ho R, et al. Association between dual orexin receptor antagonists (DORAs) and suicidality: reports to the United States Food and Drug Administration Adverse Event Reporting System (FAERS).. Expert opinion on drug safety. 2025;24(6):753-757. doi:10.1080/14740338.2024.2361300 PMID:38804896.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "receptor" ], "implication_evidence": [ "BACKGROUND: Package inserts for the FDA-approved dual orexin receptor antagonists (DORAs) suvorexant, lemborexant and daridorexant state that suicide risk should be monitored." ], "safety_vocabulary_found": [ "adverse", "event", "risk", "suicidal", "suicidality" ] }, "pmid": "38804896", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Kaufmann P, Muehlan C, Anliker-Ort M, Sabattini G, Siebers N, Dingemanse J. Transfer of the Dual Orexin Receptor Antagonist Daridorexant into Breast Milk of Healthy Lactating Women.. Journal of clinical pharmacology. 2024;64(10):1278-1287. doi:10.1002/jcph.2455 PMID:38736033.", "decision": "EXCLUDE", "evidence": { "reason_detail": "the medicine appears only as background; no reported adverse event is attributed to it in any sentence", "safety_vocabulary_found": [ "risk", "safety", "safety profile", "somnolence", "tolerability" ] }, "pmid": "38736033", "reason": "X4 — DRUG_NOT_IMPLICATED: the medicine is mentioned, but no reported adverse event is attributed to it.", "reason_code": "X4" }, { "citation": "Ranteh O, Tedasen A, Rahman MA, Ibrahim MA, Sama-Ae I. Bioactive compounds from Ocimum tenuiflorum and Poria cocos: A novel natural Compound for insomnia treatment based on A computational approach.. Computers in biology and medicine. 2024;175:108491. doi:10.1016/j.compbiomed.2024.108491 PMID:38657467.", "decision": "EXCLUDE", "evidence": { "reason_detail": "the medicine appears only as background; no reported adverse event is attributed to it in any sentence", "safety_vocabulary_found": [ "adverse", "risk", "toxicity" ] }, "pmid": "38657467", "reason": "X4 — DRUG_NOT_IMPLICATED: the medicine is mentioned, but no reported adverse event is attributed to it.", "reason_code": "X4" }, { "citation": "Di Marco T, Djonlagic I, Dauvilliers Y, Sadeghi K, Little D, Datta AN, et al. Effect of daridorexant on sleep architecture in patients with chronic insomnia disorder: a pooled post hoc analysis of two randomized phase 3 clinical studies.. Sleep. 2024;47(11):zsae098. doi:10.1016/j.ijpsycho.2021.07.626 PMID:38644625.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "participants", "patients" ], "implication_evidence": [ "CLINICAL TRIALS: ClinicalTrials.gov NCT03545191: study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants with insomnia disorder.", "URL: Study Details | study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants with insomnia disorder | ClinicalTrials.gov ClinicalTrials.gov NCT03575104:study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants who experience difficulties sleeping.", "URL: study details | study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants who experience difficulties sleeping | ClinicalTrials.gov." ], "safety_vocabulary_found": [ "safety" ] }, "pmid": "38644625", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Álamo C, Sáiz Ruiz J, Zaragozá Arnáez C. Orexinergic Receptor Antagonists as a New Therapeutic Target to Overcome Limitations of Current Pharmacological Treatment of Insomnia Disorder.. Actas espanolas de psiquiatria. 2024;52(2):172-182. doi:10.62641/aep.v52i2.1659 PMID:38622003.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "receptor" ], "implication_evidence": [ "Dual orexin receptor antagonists (DORAs) such as daridorexant, lemborexant, and suvorexant, represent a novel approach to insomnia treatment by inhibiting wakefulness rather than enhancing sedation.", "As the only DORA approved for insomnia treatment by the European Medicines Agency (EMA) and Food and Drug Administration (FDA), daridorexant has demonstrated sustained efficacy over a 12-month period, improving nocturnal sleep parameters and daytime functionality, with a favorable safety and tolerability profile." ], "safety_vocabulary_found": [ "risk", "safety", "sedation", "tolerability", "unfavorable" ] }, "pmid": "38622003", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Kim WJ, Kim HS. Emerging and upcoming therapies in insomnia.. Translational and clinical pharmacology. 2024;32(1):1-17. doi:10.12793/tcp.2024.32.e5 PMID:38586124.", "decision": "EXCLUDE", "evidence": { "reason_detail": "the medicine appears only as background; no reported adverse event is attributed to it in any sentence", "safety_vocabulary_found": [ "abuse", "dependence", "safety" ] }, "pmid": "38586124", "reason": "X4 — DRUG_NOT_IMPLICATED: the medicine is mentioned, but no reported adverse event is attributed to it.", "reason_code": "X4" }, { "citation": "Vecchierini MF, Léger D. [Pharmacotherapies for insomnia].. La Revue du praticien. 2024;74(3):297-302 PMID:38551874.", "decision": "EXCLUDE", "evidence": { "reason_detail": "the medicine appears only as background; no reported adverse event is attributed to it in any sentence", "safety_vocabulary_found": [ "abuse", "adverse", "event", "risk", "sedation", "somnolence" ] }, "pmid": "38551874", "reason": "X4 — DRUG_NOT_IMPLICATED: the medicine is mentioned, but no reported adverse event is attributed to it.", "reason_code": "X4" }, { "citation": "Cicala G, Barbieri MA, Russo G, Salvo F, Spina E. Safety of Dual Orexin Receptor Antagonist Daridorexant: A Disproportionality Analysis of Publicly Available FAERS Data.. Pharmaceuticals (Basel, Switzerland). 2024;17(3):342. doi:10.1007/s40801-021-00278-z PMID:38543128.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "pharmacovigilance", "real-world", "receptor" ], "implication_evidence": [ "Safety of Dual Orexin Receptor Antagonist Daridorexant: A Disproportionality Analysis of Publicly Available FAERS Data.", "These data provide valuable insights into the real-world safety profile of daridorexant, supporting the existence of safety signals related to nightmares, depression, and hangovers." ], "safety_vocabulary_found": [ "adr", "adverse", "adverse drug reaction", "event", "events", "reaction", "safety", "safety profile" ] }, "pmid": "38543128", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Zenklusen I, Dingemanse J, Reh C, Gehin M, Kaufmann P. Effect of Daridorexant on the Pharmacokinetics of Midazolam, and on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Male Subjects.. Drugs in R&D. 2024;24(1):97-108. doi:10.1002/PSP4.12877 PMID:38472696.", "decision": "EXCLUDE", "evidence": { "reason_detail": "the medicine appears only as background; no reported adverse event is attributed to it in any sentence", "safety_vocabulary_found": [ "safety", "tolerability" ] }, "pmid": "38472696", "reason": "X4 — DRUG_NOT_IMPLICATED: the medicine is mentioned, but no reported adverse event is attributed to it.", "reason_code": "X4" }, { "citation": "Fornaro M, Caiazza C, Rossano F, Cilmi F, De Prisco M, Vieta E, et al. Residual effects of medications for sleep disorders on driving performance: A systematic review and network meta-analysis of randomized controlled trials: NMA driving and hypnotics.. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. 2024;81:53-63. doi:10.1016/j.euroneuro.2024.01.011 PMID:38401406.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "healthy", "subjects" ], "publication_types": [ "journal article", "network meta-analysis", "systematic review" ] }, "pmid": "38401406", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Fernandes M, Placidi F, Mercuri NB, Liguori C. Daridorexant treatment for chronic insomnia: a real-world retrospective single-center study.. Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2024;45(7):3443-3448. doi:10.1016/j.smrv.2020.101332 PMID:38280086.", "decision": "INCLUDE", "evidence": { "human_evidence": [ "patient", "patients", "real-world", "receptor", "retrospective" ], "implication_evidence": [ "This retrospective observational study aimed to describe real-world data on daridorexant effectiveness and safety in adult patients with CID.", "CONCLUSIONS: This study suggests daridorexant to be effective and safe in real-world CID treatment whether used as a first-ever treatment, switch, or add-on, as reflected by subjective and objective measures and the absence of serious treatment-related adverse events." ], "safety_vocabulary_found": [ "adverse", "events", "safety", "symptoms" ] }, "pmid": "38280086", "reason": "INCLUDE — INCLUDED: human record in which the medicine is implicated in a reported adverse event, tolerability or safety finding.", "reason_code": "INCLUDE" }, { "citation": "Na HJ, Jeon N, Staatz CE, Han N, Baek IH. Clinical safety and narcolepsy-like symptoms of dual orexin receptor antagonists in patients with insomnia: a systematic review and meta-analysis.. Sleep. 2024;47(2):zsad293. doi:10.1093/sleep/zsad293 PMID:37950346.", "decision": "EXCLUDE", "evidence": { "human_evidence": [ "discontinuation", "patients", "receptor" ], "publication_types": [ "journal article", "meta-analysis", "research support, non-u.s. gov't", "systematic review" ] }, "pmid": "37950346", "reason": "X2 — NO_NEW_CASES: a review, editorial, comment, guideline or meta-analysis carrying no new case data.", "reason_code": "X2" }, { "citation": "Anliker-Ort M, Dingemanse J, Janů L, Kaufmann P. Effect of Daridorexant on the Pharmacokinetics of P-Glycoprotein Substrate Dabigatran Etexilate and Breast Cancer Resistance Protein Substrate Rosuvastatin in Healthy Subjects.. Clinical drug investigation. 2023;43(11):827-837. doi:10.1007/s40261-023-01310-6 PMID:37858005.", "decision": "EXCLUDE", "evidence": { "reason_detail": "the medicine appears only as background; no reported adverse event is attributed to it in any sentence", "safety_vocabulary_found": [ "safety" ] }, "pmid": "37858005", "reason": "X4 — DRUG_NOT_IMPLICATED: the medicine is mentioned, but no reported adverse event is attributed to it.", "reason_code": "X4" }, { "citation": "Muehlan C, Roch C, Vaillant C, Dingemanse J. The orexin story and orexin receptor antagonists for the treatment of insomnia.. 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