ramelteon / Generic mfg. - LARVOL DELTA

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

Real-world data on the abuse potential of medications for the treatment of insomnia (WSS 2025) - "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 abuse, misuse, overdose, dependence and withdrawal for DORAs compared with drugs typically prescribed long term for insomnia treatment. This included benzodiazepines (both indicated for and used off label) as well as z-drugs. The DORA class had significantly lower odds of reporting for adverse events denoting drug abuse when compared with both the scheduled drug zolpidem and the non-scheduled drug trazodone."

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

Bridging the Guideline Gap: Clinically Tested Casein Tryptic Hydrolysate (CTH) and the Combination of CTH-Theanine as First-Line Therapy for Mild to Moderate Insomnia (WSS 2025) - "When the CBT-I approach is not effective, pharmacological intervention can be offered as a short-term (≤ 4 weeks) approach, prescribing benzodiazepines, benzodiazepine receptor agonists, daridorexant, and low-dose sedating antidepressants; a longer-term approach (up to 3 months) with orexin receptor antagonists or prolonged-release melatonin, considering their advantages and disadvantages. Materials and Antihistamines, antipsychotics, fast-release melatonin, ramelteon, and phytotherapeutics are not recommended for insomnia, as indicated by the recent European Insomnia Guideline... In contrast to many pharmacological options, both CTH and CTH-theanine formulations consistently exhibit favourable safety profiles, positioning them as compelling candidates for first-line therapy when CBT-I is inadequate. Larger, multinational trials are warranted to further validate these findings and support broader clinical adoption."

Clinical • Anesthesia • CNS Disorders • Insomnia • Sleep Disorder

Ultra-low-dose ramelteon is useful for non-24-h sleep-wake rhythm disorder in a severe psychomotor handicapped child. (PubMed, Pediatr Int) - No abstract available

Journal • Sleep Disorder

Association between sleep disorder and delirium in adult patients undergoing cardiac surgery: a retrospective cohort study. (PubMed, BMC Anesthesiol) - "Although sleep disorders did not show significant associations with postoperative delirium in patients undergoing cardiac surgery based on MIMIC database, sleep screening should remain an integral part of a comprehensive perioperative risk assessment. Delirium is an independent risk factor for increased mortality and increased healthcare resource consumption. The core of clinical management should focus on early identification and efficient intervention of postoperative delirium."

Journal • Retrospective data • Cardiovascular • CNS Disorders • Cognitive Disorders • Sleep Disorder

Adverse events of pharmacological interventions for insomnia disorder in adults: a systematic review and network meta-analysis. (PubMed, Front Psychiatry) - "Compared with placebo, zolpidem (somnolence: relative risk [RR] 1.85; dizziness: RR 2.33; headache: RR 1.26), zopiclone (somnolence: RR 2.02; dizziness: RR 2.33; dysgeusia: RR 7.84), indiplon (somnolence: RR 3.46; dizziness: RR 2.30; headache: RR 1.63), gaboxadol (dizziness: RR 3.44), eszopiclone (somnolence: RR 2.00; dizziness: RR 3.18; dysgeusia: RR 10.54), estazolam (somnolence: RR 2.08), flunitrazepam (somnolence: RR 3.04), flurazepam (somnolence: RR 2.52), lemborexant (somnolence: RR 6.57), nitrazepam (somnolence: RR 3.80), Ramelteon (somnolence: RR 2.19), suvorexant (somnolence: RR 3.32), Temazepam (somnolence: RR 3.77), trazodone (somnolence: RR 2.86), triazolam (somnolence: RR 2.35), and esmirtazapine (somnolence: RR 4.63; dizziness: RR 2.87) had the most harmful profile in nervous system disorders...Data on some drugs like flurazepam, nitrazepam, triazolam, and zaleplon in some outcomes were mainly based on limited study with rare event and thus was highly..."

Adverse events • Journal • Retrospective data • Review • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Infectious Disease • Insomnia • Otorhinolaryngology • Pain • Psychiatry • Respiratory Diseases • Sinusitis • Sleep Disorder • Xerostomia

Association between ramelteon use and risk of fragility fractures: A retrospective cohort study. (PubMed, Arch Osteoporos) - "In a real-world setting, short- to mid-term ramelteon use was not associated with an increased risk of fractures. Future studies should consider longer follow-up periods to further investigate the effects of ramelteon on bone health."

Journal • Retrospective data • Musculoskeletal Diseases • Orthopedics • Osteoporosis • Rheumatology

Melatonin Use in the ICU: A Systematic Review and Meta-Analysis. (PubMed, Crit Care Med) - "Our findings suggest that melatonin administration in the critically ill may improve perceived sleep and reduce delirium, without increasing adverse effects. Certainty of evidence was negatively affected by the risk of bias and inconsistency. Future RCTs should focus on identifying optimal dosing, administration timing, improving measurements of sleep outcomes, and target populations."

Clinical • Journal • Retrospective data • CNS Disorders • Critical care • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry

Safety profile of ramelteon from the perspective of physicians and pharmacists: a 20-year real-world pharmacovigilance analysis based on the FAERS database. (PubMed, BMC Psychiatry) - "Our study reveals a broad spectrum of AEs associated with ramelteon, including unique sensory experiences (e.g., hangover, derealisation, feeling drunk), reproductive system effects (e.g., decreased libido, priapism), hallucination-related AEs (e.g., visual hallucinations), and rare but clinically significant reactions (e.g., glossoptosis, restless legs syndrome, and photopsia). These findings expand the current understanding of ramelteon's safety and underscore the importance of closely monitoring patients' responses during treatment. Emphasis should be placed on individualized treatment strategies and strengthened pharmacovigilance."

Adverse events • Journal • Real-world evidence • CNS Disorders • Insomnia • Mental Retardation • Movement Disorders • Psychiatry • Restless Legs Syndrome • Sleep Disorder

Global burden of insomnia medication-associated suicidality, 1967-2024: A disproportionality analysis of the global pharmacovigilance database. (PubMed, Psychiatry Res) - "Although this disproportionality analysis did not permit causal interpretation, our study highlights significant variations in suicidality signal risk among insomnia medications, with benzodiazepines, Z-drugs, antidepressants, and first-generation H1 antagonists posing stronger signal, and dual orexin receptor antagonists presenting a weaker signal. Given the limitations of pharmacovigilance data, further studies are needed to confirm these findings and guide safer prescribing practices, particularly for individuals at high risk of suicidality."

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

Evaluating machine learning algorithms for prediction of treatment response for sleep disturbances in patients with schizophrenia: A post-hoc analysis from a randomized controlled trial. (PubMed, Psychiatr Danub) - P4 | "Machine learning models are an emerging trend in clinical research and should be translated into clinical practice. The logistic regression model predicted responders with 90% accuracy."

Clinical • Journal • Retrospective data • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia • Sleep Disorder

Efficacy of Ramelteon, Suvorexant, and Lemborexant for Delirium Prevention in Hospitalized Patients: A Systematic Review and Meta-Analysis. (PubMed, Crit Care Med) - "Sleep-wake regulating pharmacologic agents were associated with 40%-46% relative risk reductions in delirium prevalence, based on low-certainty evidence. Although these findings are promising, the absence of credible subgroup effects limits conclusions about the comparative efficacy of individual agents. Further, high-quality, prospective trials are needed to confirm these results and to clarify the role of specific pharmacologic strategies in delirium prevention."

Journal • Retrospective data • CNS Disorders

Ramelteon reduced anxiety/depression and sleep problems among shift ​workers (CINP-AsCNP 2025) - "Our preliminary open-label trial was the first to show ramelteon, a pure melatonin agonist, could reduce both anxiety/depression and sleep quality. The circadian rhythm might play a role of the presence of anxiety/depression among shift workers. The circadian rhythm and mental condition of shift workers can be regularly monitored and evaluated."

CNS Disorders • Depression • Fatigue • Mood Disorders • Psychiatry • Sleep Disorder • Sleep Wake Cycle Disorder