ramelteon / Generic mfg. - LARVOL DELTA

Melatonin or ramelteon for the prevention of postoperative delirium in elderly patients: A systematic review and meta-analysis of randomized clinical trials. (PubMed, J Clin Anesth) - "Perioperative melatonin was associated with reduced POD in elderly surgical patients, with an apparent dose-response at ≥5 mg. Ramelteon did not demonstrate benefit in the available trials. Given heterogeneity and low certainty, findings-especially dose effects-should be interpreted cautiously."

Clinical • Journal • Retrospective data • Review • Anesthesia • CNS Disorders • Geriatric Disorders • Pain

Real-world data on the abuse potential of medications for the treatment of insomnia: a disproportionality analysis of the FAERS database. (PubMed, Front Pharmacol) - "Drugs of interest included Schedule IV drugs (benzodiazepines, Z-drugs, dual orexin receptor antagonists [DORAs]) and non-scheduled drugs (trazodone, doxepin, ramelteon)...This study identified significantly fewer reported cases of real-world abuse, misuse, overdose, and other safety risks for DORAs compared with the unscheduled drug trazodone and scheduled Z-drugs. This suggests that categorization of DORAs as Schedule IV drugs may overstate their abuse potential."

Journal • Real-world evidence • CNS Disorders • Insomnia • 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

Melatonin Agonist for Shift-time Workers. (clinicaltrials.gov) - P4 | N=61 | Completed | Sponsor: Tri-Service General Hospital

New P4 trial • Sleep Disorder

Impact of the Medical Policy Intervention for Polypharmacy on Long-Term Prescriptions of Hypnotic Medications in Older Patients: An Interrupted Time-Series Analysis Using a Nationwide Claims Database in Japan. (PubMed, Geriatr Gerontol Int) - "The medical fee revisions related to polypharmacy significantly redirected the long-term prescription trends of BZDs, z-drugs, and ramelteon/ORAs toward a decline."

Journal

Melatonin supplementation reduces delirium incidence in critically ill patients: a systematic review and meta-analysis. (PubMed, Front Pharmacol) - "Only RCTs comparing melatonin or ramelteon with placebo or standard care in adult ICU patients were included...These findings support the use of melatonin for delirium prevention but suggest its benefits may be limited to reducing occurrence rather than altering the course of established delirium or other clinical outcomes. https://osf.io/95je7."

Journal • Retrospective data • Review • CNS Disorders • Critical care • Psychiatry

Pharmacologic Modulation of Circadian Rhythms for Delirium Prevention: An Age-Stratified Systematic Review and Meta-Analysis. (PubMed, J Am Geriatr Soc) - "Sleep-wake pharmacotherapies may reduce incident delirium in hospitalized adults. In randomized trials, melatonin and ramelteon did not significantly reduce delirium incidence, whereas dual orexin receptor antagonists showed a possible benefit, but the meta-regression did not demonstrate a reliable between-class difference, and the evidence remains limited. Adequately powered randomized trials across inpatient settings are needed to clarify any true differences and define clinical relevance."

Journal • Retrospective data • Review • CNS Disorders

Evaluating the Safety of Prescription Sleep Medications in Patients Undergoing Total Knee Arthroplasty: A Propensity Matched Analysis. (PubMed, J Am Acad Orthop Surg) - "Use of any prescription sleep medication or only standard sleep medications is associated with increased surgical complications. Additional research is needed to find medications that may be safer for routine postoperative use."

Journal • CNS Disorders • Musculoskeletal Diseases • Orthopedics • Pain • Psychiatry • Sleep Disorder

Can We Develop Glioma Subtype-Specific Precision Medicines? An Integrative Machine Learning Pipeline for Biomarker Discovery and Drug Repurposing for Glioblastoma and Low-Grade Glioma. (PubMed, OMICS) - "Repurposed drug candidates were then predicted via signature-based prioritization and evaluated using molecular docking simulations, revealing six promising compounds for GBM (vandetanib, capecitabine, melatonin, agomelatine, ramelteon, and tasimelteon) and one for LGG (ambroxol). This study demonstrates the utility of combining class-balancing, feature selection, and drug repurposing pipelines to uncover clinically relevant glioma biomarkers and therapeutic candidates, thus providing a computational foundation for future experimental and translational validation in these brain cancers and neuro-oncology."

Biomarker • Journal • Brain Cancer • Glioblastoma • Glioma • Oncology • Solid Tumor • ANK3

A Pharmacoepidemiological Indicator for Detecting Potential Regional Overuse of Hypnotics in Japan: A Cross-Sectional Study. (PubMed, Cureus) - "Population-adjusted prescription volumes of ramelteon, suvorexant, and lemborexant were obtained from the National Database of Health Insurance Claims. Conclusions Regional prescription volumes of circadian-related hypnotics can, to some extent, be anticipated from environmental determinants such as sunlight duration. The proposed indicator-based pharmacoepidemiological framework may help identify regions at risk of potential overuse and guide climate-sensitive strategies for optimizing hypnotic use in older adults."

Journal • Observational data

Assessing the Efficacy of Ramelteon in the Management of Insomnia among Veterans with Previous Melatonin Ineffectiveness (ASHP 2025) - No abstract available

Clinical • CNS Disorders • Insomnia • Sleep Disorder

Ramelteon versus Doxepin for Insomnia in Older Adults: A Comparative Literature Review and Evidence Synthesis (ASHP 2025) - No abstract available

Clinical • Review • CNS Disorders • Insomnia • Sleep Disorder

A scalable natural language processing framework for drug repurposing in chemotherapy-induced adverse events from clinical narrative records. (PubMed, Eur J Cancer) - "This study introduces a scalable NLP-epidemiology framework for non-invasive, real-world validation of drug repurposing candidates. The ARB finding provides human-level PoC evidence supporting prospective clinical testing, while the ramelteon signal warrants further exploration. Our approach demonstrates how EHR narratives can operationalize translational research, prioritizing safe, accessible agents for improving the tolerability of cancer treatment."

Adverse events • Journal • Mucositis • Oncology • Pain • Stomatitis

Targeted interventions to promote sleep for hospitalized older adults: a narrative review. (PubMed, Hosp Pract (1995)) - "Sleep promotion should include, at a minimum, non-pharmacological interventions (e.g. increasing familiarity, reducing sensory stimulation as bedtime approaches, maintaining environmental and behavioral zeitgebers). Pharmacological (e.g. ramelteon, trazadone, doxepin, dual orexin receptor antagonists) and nutraceutical (e.g. melatonin, magnesium) interventions may be appropriate, Certain pharmacological options are considered potentially unsafe for older adults (e.g. benzodiazepines, Z-drugs, antihistamines) and should be avoided in this population."

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

Exploring the mechanism of BuNao AnShen Capsules in the treatment of insomnia based on network pharmacology and experimental validation. (PubMed, J Ethnopharmacol) - "This study confirmed the sedative-hypnotic efficacy of BNASC and revealed its underlying mechanisms related to neurotransmitters, inflammatory cytokines, and oxidative stress, providing a theoretical basis for its clinical application."

Journal • CNS Disorders • Inflammation • Insomnia • Sleep Disorder • IL1B • IL6 • TNFA

Molecular docking and dynamic simulation of melatonin interaction with insulin-like growth factor, mechanistic target of rapamycin, and ecdyson receptor proteins in mud crab (Scylla spp.): implications for growth regulation. (PubMed, Braz J Biol) - "Molecular docking revealed strong binding affinities of melatonin with IGF (-5.7 kcal/mol), mTOR (-5.7 kcal/mol), and EcR (-6.0 kcal/mol), comparable to or exceeding that of the reference ligand, ramelteon. Molecular dynamics simulations further confirmed the structural stability of the melatonin-protein complexes, with RMSF values below 3 Å at key residues. These findings provide foundational insights into the molecular basis of melatonin's growth-regulatory potential in crustaceans and propose IGF as candidate targets for future in vivo studies in aquaculture applications."

Journal • mTOR

Ramelteon Ameliorates Isoflurane-Induced Hyperactivity and Social-Recognition Impairment in Aged Mice. (PubMed, J Integr Neurosci) - "Isoflurane anesthesia combined with abdominal surgery was associated with prolonged hyperactivity and impaired social recognition, although other cognitive domains such as working memory appeared to remain unaffected. Ramelteon appeared to alleviate these behavioral and neuroinflammatory changes, suggesting its potential for preventing certain postoperative neurobehavioral alterations."

Journal • Preclinical • Anesthesia • CNS Disorders • Cognitive Disorders • IL1B

Z-drug abuse and dependence: clinical guideline of the Brazilian Academy of Neurology for diagnosis and management. (PubMed, Arq Neuropsiquiatr) - "An advisory committee, consisting of neurologists from the Brazilian Academy of Neurology (Academia Brasileira de Neurologia, ABN, in Portuguese) and psychiatrists specializing in substance-use disorders, contributed to the selection and organization of the scientific literature and took part in the voting process. Key recommendations were established: 1) prior to discontinuation, a comprehensive assessment of mental status, psychiatric and sleep comorbidities, and the degree of pharmacological dependence is essential; 2) gradual tapering is advised; 3) non-pharmacological interventions, such as cognitive behavioral therapy for insomnia, are recommended, and acceptance and commitment therapy, which is optional, may be incorporated; 4) for zolpidem withdrawal, adjunctive pharmacotherapy, which is optional, may include trazodone, other antidepressants, quetiapine or other antipsychotics, alpha-2-delta (α2δ) ligands, or alternative hypnotics (such as ramelteon, zopiclone,..."

Clinical guideline • Journal • Review • CNS Disorders • Insomnia • Psychiatry • Sleep Disorder

Self-reported sleep variables, sleep quality, and quality of life assessment in transition to lemborexant in patients with Insomnia: the multicenter, open-label SOMNUS study. (PubMed, Sleep Med X) - P4 | "The prospective, nonrandomized, open-label, multicenter SOMNUS Study analyzed data from 90 patients across four cohorts of direct switching to lemborexant from Z-drugs (monotherapy cohort: n = 25), suvorexant (monotherapy cohort: n = 25, combination cohort: n = 21), and ramelteon (combination cohort: n = 19) up to 14 weeks. These findings indicate that transitioning to lemborexant from previous insomnia treatment is efficacious in improving sleep parameters, insomnia severity, and health-related quality of life, with a favorable safety profile. NCT04742699."

HEOR • Journal • CNS Disorders • Insomnia • Sleep Disorder

Investigating the impact of ramelteon on all-cause mortality in ischemic stroke ICU patients: a retrospective propensity-matched study from the MIMIC-IV database. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "Through subgroup and sensitivity analyses, the associations were confirmed to be consistent across different clinical strata. In critically ill patients with ischemic stroke, ramelteon usage was independently associated with lower short- and long-term all-cause mortality."

Journal • Retrospective data • Cardiovascular • Critical care • Ischemic stroke

Falls and fractures associated with ramelteon use: A systematic review and meta-analysis. (PubMed, Gen Hosp Psychiatry) - "Ramelteon was not associated with a statistically significant increase in the risk of falls or fractures, regardless of the study design."

Journal • Retrospective data • Review • Musculoskeletal Diseases • Orthopedics

The Efficacy of Melatonergic Receptor Agonists Used in Clinical Practice in Insomnia Treatment: Melatonin, Tasimelteon, Ramelteon, Agomelatine, and Selected Herbs. (PubMed, Molecules) - "It also examines their functional interplay with serotonergic, GABAergic, dopaminergic, and orexinergic systems involved in arousal and sleep regulation. Through comparative synthesis of pharmacokinetics and neurochemical mechanisms, this work aims to inform the development of evidence-based strategies for the treatment of insomnia and circadian rhythm sleep-wake disorders."

Journal • Review • CNS Disorders • Insomnia • Sleep Disorder • Sleep Wake Cycle Disorder

Sequence Symmetry Analysis of the Interrelationships Between Ramelteon and Parkinson's Disease. (PubMed, J Pineal Res) - "However, even though this study used real-world data, these results should be interpreted with caution, as a sequence symmetry analysis cannot be adjusted for covariates. Therefore, additional pharmacoepidemiological studies are needed to further verify the potential risk of Parkinson's disease associated with ramelteon use."

Journal • Alzheimer's Disease • CNS Disorders • Movement Disorders • Parkinson's Disease

Efficacy and Safety of Ramelteon in the Reduction of Delirium and Duration of ICU Stay: A Randomized Placebo-Controlled Trial. (PubMed, Cureus) - "While its impact on delirium incidence was not statistically significant, the findings suggest a potential benefit in mitigating delirium severity and enhancing recovery. Further large-scale studies are needed to confirm these results."

Journal • CNS Disorders • Critical care • Sleep Disorder

Real-World Treatment Patterns of Sleep Medications in the United States Veterans Affairs Health System (WSS 2025) - "Overall, an estimated 2.6% were prescribed zolpidem, 0.7% temazepam, 0.28% eszopiclone, 0.12% ramelteon, 0.6% zaleplon, 0.5% suvorexant, 0.4% triazolam, 0.006 lemborexant, 0.005% estazolam, and 0.0001% daridorexant. The Z-drug zolpidem was the most commonly prescribed medication indicated for insomnia. Sedative antidepressants were also frequently utilized, likely due to their affordability and the lack of widely accepted, cost-effective alternatives for managing insomnia. This reliance on off-label agents such as trazodone suggests a potential gap between clinical guidelines and real-world practice, possibly reflecting formulary constraints, prescriber familiarity, or patient comorbidities."

Clinical • HEOR • Real-world • Real-world evidence • CNS Disorders • Insomnia • Sleep Disorder