Dayvigo (lemborexant) / Eisai - LARVOL DELTA

Unveiling the binding mechanism of orexin 2 receptor antagonists with computational chemistry. (PubMed, Phys Chem Chem Phys) - "In this study, we investigated the molecular interactions of three dual orexin receptor antagonists (daridorexant, lemborexant, suvorexant) and the selective OXR2 antagonist seltorexant using an integrated computational approach that combined classical molecular docking, explicit-membrane molecular dynamics (MD) simulations of 700 ns, and quantum-based molecular fractionation with conjugate caps (MFCC) calculations coupled with density functional theory (DFT) at the B97D/6-311+G(d,p) level. These findings shed light on the structural and energetic factors that determine OXR2-ligand recognition. The results provide a solid molecular framework for the rational optimization of orexin receptor antagonists with enhanced selectivity and improved pharmacological profiles."

Journal • CNS Disorders • Mental Retardation • Psychiatry

Treatment Options for Sleep Disturbances in Dementia: A Systematic Review. (PubMed, J Geriatr Psychiatry Neurol) - "Z-drug eszopiclone, low-dose ORA lemborexant, and social stimulation PARO show the most favorable profile across outcomes and benchmarks, but pharmacological options require careful risk-benefit consideration. No external funding. The review was registered in INPLASY: https://doi.org/10.37766/inplasy2025.1.0097."

Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Sleep Disorder

Effects of Lemborexant on Motor-sleep Comorbidity in Parkinson's Disease (clinicaltrials.gov) - P4 | N=44 | Recruiting | Sponsor: YangPan | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Insomnia • Movement Disorders • Parkinson's Disease • Sleep Disorder

Restoring sleep in cirrhosis: A prospective three arm double blind randomized clinical trial of lemborexant efficacy and hepatic safety (APASL 2026) - No abstract available

Clinical • Fibrosis • Hepatology • Immunology

Efficacy and Safety of Lemborexant for Patients With Cirrhosis and Sleep Problems (clinicaltrials.gov) - P2 | N=82 | Completed | Sponsor: Indonesia University

New P2 trial • CNS Disorders • Fibrosis • Gastroenterology • Hepatic Encephalopathy • Hepatology • Immunology • Insomnia • Liver Cirrhosis • Sleep Disorder

Effect of Lemborexant Coadministration on Clozapine Concentration-to-Dose Ratios: A Within-Subject Therapeutic Drug Monitoring Series. (PubMed, J Clin Psychopharmacol) - No abstract available

Journal

Involvement of orexin nerves in early stage of Alzheimer's disease model mice and preventive effect of orexin receptor antagonists. (PubMed, J Alzheimers Dis) - "Furthermore, both drugs suppressed the accumulation of Aβ in the CA1 region of the hippocampus in App-KI mice. This was associated with increased Aβ uptake by activated microglia.ConclusionsThe results suggest that suvorexant and lemborexant effectively suppresses the early stages of AD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Acceptability of suvorexant versus lemborexant: An inverse probability of treatment weighting analysis. (PubMed, J Psychiatr Res) - "However, the discontinuation rate due to lack of efficacy was significantly lower for lemborexant (4.9%; 38/768) compared to suvorexant (7.1%; 23/323), with an odds ratio of 0.63 (95% confidence interval, 0.48-0.83). This exploratory finding suggests a potential difference in treatment acceptability associated with efficacy between suvorexant and lemborexant in routine clinical practice, warranting further investigation."

Journal • CNS Disorders • Insomnia • Psychiatry • Sleep Disorder

Effects of Pharmacologic Interventions on Objective Sleep Architecture and Continuity in Alzheimer's Disease: A Network Meta-analysis of Randomized Trials (AAN 2026) - "Improvement in sleep efficiency was statistically significant for Suvorexant (MD 5.8 [1.99,9.61]) and numerically significant for Lemborexant(2.5-5 mg). Suvorexant demonstrated the most consistent efficacy, with statistical significance for increasing total sleep time, sleep efficiency and reduced wakefulness after sleep onset. Lembroxeant had modest effects on sleep efficiency, while zolpidem and zopiclone ranked highest for reducing night awakenings without statistical significance. With such therapeutic potential for enhancing sleep continuity by Suvorexant, further long-term trials could confirm sustained benefits and safety"

Retrospective data • Alzheimer's Disease • CNS Disorders • Sleep Disorder

Does Treatment for Insomnia Improve Sleep State Misperception? (AAN 2026) - "Background: Discrepancies often exist between patient-reported (subjective) and PSG-assessed (objective) sleep data, yet few insomnia studies have examined the effects of treatment on sleep state misperception.Design/ E2006-G000-304: 1-month, randomized, double-blind study of LEM 5mg (LEM5), LEM 10mg (LEM10), placebo (PBO), and zolpidem extended-release (ZOL) 6.25mg in participants with insomnia disorder aged ≥55 years. While many participants with insomnia became more accurate in reporting their sleep parameters with treatment, sleep state misperception persisted in many individuals despite improvement in sleep."

CNS Disorders • Insomnia • Sleep Disorder

Interpreting Adverse Events of Somnolence With Lemborexant in Clinical Trials (AAN 2026) - P1, P3 | "Incidence of somnolence was dose-dependent, but patients are advised to start on LEM5. The probability of reporting somnolence diminished after the first 2 weeks. LEM10 was not associated with driving impairment, suggesting TEAE-S do not equate with impairment."

Adverse events • Clinical • CNS Disorders • Insomnia • Sleep Disorder

Comparative Effects of Pharmacologic Interventions on Subjective and Functional Sleep-Wake Outcomes in Alzheimer's Disease: A Network Meta-Analysis of Randomized Controlled Trials (AAN 2026) - "For daytime sleep regulation, orexin receptor antagonists (lemborexant) showed promising effects, with lemborexant 10mg demonstrating MD 76.58 [-7.64; 160.80]. Melatonin consistently improved nocturnal sleep and circadian rhythm on subjective measures, with dose-dependent ranking advantages across networks. Dual orexin receptor antagonists showed promising sleep maintenance signals but needed confirmation for daytime effects and longer-term outcomes, while galantamine offered minimal sleep benefit. These network-based hierarchies enable targeted pharmacotherapy and elevate restorative sleep in AD."

Retrospective data • Alzheimer's Disease • CNS Disorders • Sleep Disorder

Beyond the Gut: A Case Report of Antibiotic-Induced Dysbiosis as a Hidden Cause of Chronic Insomnia. (PubMed, Cureus) - "Several months later, he developed severe insomnia, unresponsive to melatonin, mirtazapine, CBT-I, and multiple hypnotics, including zolpidem and lemborexant. Clinicians should consider gut microbiome assessment in persistent insomnia, particularly in patients with extensive antibiotic exposure. Further research is warranted to elucidate mechanisms and validate microbiome-targeted therapies."

Journal • Acute Lymphocytic Leukemia • CNS Disorders • Hematological Malignancies • Insomnia • Leukemia • Oncology • Sleep Disorder • Transplantation

Lemborexant in Delayed Sleep Phase Syndrome (clinicaltrials.gov) - P4 | N=71 | Completed | Sponsor: Stanford University | Recruiting ➔ Completed | Trial completion date: Aug 2025 ➔ Jan 2026 | Trial primary completion date: Aug 2025 ➔ Jan 2026

Trial completion • Trial completion date • Trial primary completion date • Delayed Sleep Phase Disorder

A Multicenter Observational Study of Lemborexant on Insomnia Patients With Psychiatric Disorders (clinicaltrials.gov) - P=N/A | N=121 | Recruiting | Sponsor: Shanghai Mental Health Center

New trial • CNS Disorders • Insomnia • Mental Retardation • Psychiatry • Sleep Disorder

Investigation of a simple suspension method for orexin receptor antagonist tablets. (PubMed, J Pharm Health Care Sci) - No abstract available

Journal

Lemborexant for Sleep and Delirium Prevention in Elderly ICU Patients (clinicaltrials.gov) - P4 | N=100 | Not yet recruiting | Sponsor: Mahidol University

New P4 trial • CNS Disorders • Cognitive Disorders • Sleep Disorder

Comparative effects of hypnotic agents on sleep architecture and respiratory outcomes in obstructive sleep apnea: A systematic review and network meta-analysis. (PubMed, Psychiatry Clin Neurosci) - "Our network meta-analysis identified different effects of various hypnotics on sleep architecture and respiratory parameters; however, the lack of data prevented a formal synthesis of subjective outcomes. Therefore, these results should be interpreted with caution in clinical practice."

Journal • Retrospective data • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Effects of Dual Orexin Receptor Antagonists on Seizure Quality in Modified Electroconvulsive Therapy: A Pilot Study. (PubMed, J ECT) - "DORA use during m-ECT did not impair seizure quality, supporting their safe concomitant use. Findings were consistent across subgroup, agent, and dose-response analyses. Larger prospective trials are warranted to confirm these results."

Journal • CNS Disorders • Epilepsy • Insomnia • Sleep Disorder

Effects of Lemborexant on Motor-sleep Comorbidity in Parkinson's Disease (clinicaltrials.gov) - P4 | N=44 | Not yet recruiting | Sponsor: YangPan

New P4 trial • CNS Disorders • Insomnia • Movement Disorders • Parkinson's Disease • Sleep Disorder

Case Report: A case of post-viral inflammatory insomnia: observed sleep restoration associated with histamine-targeted interventions and implications for mast cell pathways. (PubMed, Front Sleep) - "Despite optimal CPAP use and multiple pharmacological trials for sleep disturbance (zolpidem, trazodone, gabapentin, diazepam, lemborexant), Oura Ring data demonstrated persistently low sleep scores, often in the 30-40 range, and minimal REM and deep sleep...At 4-week follow-up, lingering daytime fatigue and patient-reported cognitive fog prompted additional dietary modification to a low-histamine pattern and the addition of loratadine (10 mg AM) and famotidine (20 mg BID)...A multi-component intervention targeting histamine pathways, including antihistamine therapy, environmental modification, and dietary adjustment, was associated with rapid and sustained normalization of objective sleep metrics in this patient. These findings highlight the importance of evaluating immune and inflammatory contributors in patients with refractory insomnia and support further investigation of mast cell-related pathways in translational sleep medicine."

Journal • CNS Disorders • Fatigue • Inflammation • Insomnia • Sleep Disorder

Lemborexant Shift Work Treatment Study (clinicaltrials.gov) - P4 | N=29 | Completed | Sponsor: University of California, San Francisco | Recruiting ➔ Completed | N=45 ➔ 29

Enrollment change • Trial completion • CNS Disorders • Sleep Disorder

Zolpidem Withdrawal Delirium Developed as Severe Psychiatric and Physical Symptoms in a Patient With a History of Ovarian Cancer: A Case Report and Literature Review. (PubMed, Neuropsychopharmacol Rep) - "Cancer patients might be relatively more prone to zolpidem withdrawal delirium because of the possible Blood-Brain Barrier dysfunction derived from anticancer drug treatment or cancer. Oncologists and liaison psychiatrists need to prevent and detect zolpidem withdrawal delirium because it may be difficult to manage withdrawal delirium with severe psychiatric symptoms in cancer hospitals with no dedicated psychiatric ward."

Journal • Review • CNS Disorders • Gastrointestinal Disorder • Gynecology • Insomnia • Movement Disorders • Oncology • Ovarian Cancer • Pain • Psychiatry • Psychomotor Agitation • Sleep Disorder • Solid Tumor

Real-World Effectiveness, Safety, and Treatment Patterns of Lemborexant in Patients with Insomnia in Sleep Clinics: A Multicenter Prospective Cohort Study (ChiCTR) - P4 | N=1000 | Not yet recruiting | Sponsor: Xuanwu Hospital, Capital Medical University; Xuanwu Hospital, Capital Medical University

New P4 trial • CNS Disorders • Insomnia • Sleep Disorder

Lemborexant Reduces Infarct Volume and Improves Long-Term Functional Recovery in a Murine Model of Ischemic Stroke. (PubMed, bioRxiv) - "Since lemborexant is already FDA-approved for insomnia, these results could be rapidly translated into a therapeutic opportunity to improve stroke recovery through targeted sleep modulation. This approach may shift poststroke care toward integrating neurorestorative, sleep-based interventions during the subacute phase."

Journal • Preclinical • Cardiovascular • CNS Disorders • Infectious Disease • Insomnia • Ischemic stroke • Sleep Disorder