ramelteon / Generic mfg. - LARVOL DELTA

The 2025 revision of JPOS/JASCC clinical guidelines for delirium in adult patients with cancer: a summary of recommendations. (PubMed, Jpn J Clin Oncol) - "These revised clinical practice guidelines can serve as a practical framework for optimizing prevention, assessment, and management of delirium in adult patients with cancer in Japan."

Clinical guideline • Journal • CNS Disorders • Oncology • Palliative care

Circadian rhythm in platelet: an emerging therapeutic target in human diseases. (PubMed, Front Physiol) - "Third, circadian-targeting drugs including tasimelteon, ramelteon, agomelatine, SR9009, VTP-43742, and PF-670462 offer novel therapeutic strategies for rhythm-related disorders. This review highlights the circadian regulation of platelets as an emerging therapeutic target in human diseases."

Journal • Review • Cardiovascular • CNS Disorders • Hematological Disorders • Metabolic Disorders • Thrombosis • NR1D1 • RHOA

Ramelteon and Mortality in Patients With Sepsis and Cancer: Insights From a Propensity-Matched Analysis of the MIMIC-IV Database. (PubMed, Cancer Med) - "Ramelteon use was associated with lower mortality among patients with sepsis and cancer. However, given the observational design and potential residual confounding, these findings should be interpreted as hypothesis-generating and require confirmation in prospective studies."

Journal • Retrospective data • Infectious Disease • Oncology • Septic Shock

Ramelteon Mitigates Cisplatin-induced Testicular Dysfunction in Rats. (PubMed, In Vivo) - "Ramelteon mitigated acute cisplatin-induced testicular damage in rats by attenuating deterioration in sperm parameters and steroidogenesis-related changes. These findings suggest that ramelteon may be a candidate for further investigation as a strategy to mitigate acute chemotherapy-induced testicular injury."

Journal • Preclinical • CNS Disorders • Endocrine Disorders • Infertility • Insomnia • Oncology • Sexual Disorders • Sleep Disorder • CASP3 • CYP17A1 • IL6

Histological effect of melatonin and its agonist on testes in light-exposure and pinealectomized rats. (PubMed, Anat Sci Int) - "This study assessed testicular changes in MEL-deficient models and the capacity of MEL and the MEL-receptor agonist ramelteon (RAM) to ameliorate injury...This was evidenced by better preservation of seminiferous tubule architecture, reduced epithelial disorganization, and improved morphometric indices. These findings support melatonergic therapies for preserving fertility during environmental circadian disruption in adult males."

Journal • Preclinical

Pharmacological treatments of REM sleep behaviour disorder in synucleinopathies: a systematic review of effectiveness and safety. (PubMed, Sleep Med) - "pharmacological treatment of synucleinopathy-associated RBD remains supported by limited and heterogeneous evidence. Larger randomised trials using standardised clinical and vPSG outcomes are needed to clarify efficacy and safety."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Lewy Body Disease • Movement Disorders • Multiple System Atrophy • Parkinson's Disease • Psychiatry • Sleep Disorder

Pharmacological Interventions for Weight Reduction in Patients With Schizophrenia Treated With Antipsychotics: A Systematic Review and Network Meta-Analysis. (PubMed, JAMA Psychiatry) - "Other interventions including ramelteon, nizatidine, and aripiprazole were also found to be associated with weight-reducing effects but with very low certainty of evidence. This systematic review and network meta-analysis found substantial variability in weight-related outcomes across pharmacological interventions for antipsychotic-treated individuals with SSDs. Semaglutide, liraglutide, topiramate, metformin, and exenatide were associated with the greatest reductions in body weight and were supported by the highest-certainty evidence, providing guidance for clinicians managing antipsychotic-associated weight gain."

Clinical • Journal • Retrospective data • CNS Disorders • Psychiatry • Schizophrenia

Impact of early pharmacotherapy on delirium symptoms following acute stroke in older patients (CINP 2026) - "Early consecutive administration of ramelteon, suvorexant, or lemborexant within the first 48 h of hospitalization was associated with a lower likelihood of worsening delirium-related symptoms in older patients with stroke. Notably, this effect was observed despite a higher baseline prevalence of cognitive decline and previous delirium, both of which are established risk factors, in the consecutive group. The findings suggest that stabilizing the sleep–wake rhythm shortly after stroke onset may help mitigate delirium-related behavioral and cognitive disturbances."

Clinical • Cardiovascular • CNS Disorders • Cognitive Disorders • Sleep Disorder

Real-world data on the abuse potential of medications for the treatment of insomnia (CINP 2026) - "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

Effectiveness and safety of melatoninergic agonists in preventing delirium in the ICU: an updated dose‒response meta-analysis of randomized controlled trials. (PubMed, Crit Care) - "We performed a pairwise dose‒response meta-analysis of randomized controlled trials (RCTs) followed by meta-regression and trial sequential analysis to assess the ability of MEL or ramelteon (RAL) to prevent delirium in the ICU...Additionally, they appear to be safe while offering potential benefits in reducing ICU length of stay and duration of mechanical ventilation. However, the magnitude of effect was modest, with low-certainty evidence and moderate heterogeneity, and these findings should therefore be interpreted with caution."

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

Effectiveness and safety of pharmacologic agents for postoperative delirium: a narrative review. (PubMed, Curr Med Res Opin) - "Recent large-scale studies and clinical guidelines published between 2018 and 2025 reveal that neither traditional antipsychotics like haloperidol nor second-generation atypical antipsychotics like quetiapine, olanzapine, and risperidone significantly improve delirium duration, cognitive recovery, survival, or length of stay compared to a placebo...Dexmedetomidine demonstrates minimal benefit, restricted primarily to mechanically ventilated or highly agitated patients. Meanwhile, medications such as melatonin, ramelteon, orexin receptor antagonists, and ketamine have been evaluated mostly for delirium prevention rather than treatment, leaving insufficient evidence to support their use in established POD...Pharmacologic interventions should be strictly reserved for short-term behavioral control when severe agitation threatens the safety of the patient or staff. To move forward, future research must utilize standardized definitions, clearer phenotype characterizations, and..."

Journal • Review • CNS Disorders • Critical care • Psychiatry

Luzindole and ramelteon share a melatonin receptor-independent blocking effect on voltage-gated potassium KV4.2 channels. (PubMed, J Pharmacol Sci) - "Instead, specific structural features, including the methoxy group in melatonin and the furan ring in ramelteon, together with increased hydrophobicity, may be critical determinants of KV4.2 channel blockade. Collectively, these findings reveal previously unrecognized pharmacological properties of melatonin-related compounds."

Journal

Risk Factors for Delirium in Hospitalized Patients With Medical Conditions Receiving Dual Orexin Receptor Antagonists: A Retrospective Cohort Study. (PubMed, J Clin Psychopharmacol) - "Since concomitant medications represent modifiable risk factors, DORA monotherapy may be preferable for insomnia management in older hospitalized patients."

Journal • Retrospective data • Addiction (Opioid and Alcohol) • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Developmental Disorders • Insomnia • Psychiatry • Sleep Disorder • Vascular Neurology

Association between hypnotic medication use and in-hospital falls among older adults: A multicenter landmark analysis. (PubMed, PLoS One) - "Sustained hypnotic use during hospitalization was associated with a higher incidence of in-hospital falls among older adults. After adjustment for measured clinical factors and treatment selection, no significant difference in fall risk was observed between BZ/Zs and ORA/Ram."

Journal

Ramelteon for prevention of postoperative delirium in elderly cancer patients: A randomized, double-blind, placebo-controlled multicenter trial, JORTC-PON02/J-SUPPORT2103/NCCH2103. (ASCO 2026) - "In this phase III randomized controlled trial, ramelteon did not reduce the incidence of postoperative delirium in older adults undergoing major cancer surgery, and these findings do not support routine pharmacological prevention with ramelteon in this setting. Delirium within 5 days after surgery."

Clinical • Late-breaking abstract • CNS Disorders • Geriatric Disorders • Oncology

Evaluating Whether Melatonin Impacts Postoperative Sleep Following Total Joint Arthroplasty: A Systematic Review and Meta-analysis of Randomized Controlled Trials. (PubMed, Cureus) - "A search was performed utilizing the Boolean search phrase "(melatonin OR ramelteon OR tasimelteon OR agomelatine) AND (joint OR hip OR knee) AND (replacement OR arthroplasty)." Sleep duration, nightly awakenings, and patient-reported sleep outcomes were recorded when available. Melatonin does not appear to have a significant impact on postoperative sleep following TJA. Further investigation is warranted to address other factors, such as pain and environmental disturbances, to improve sleep quality."

Journal • Retrospective data • Review • CNS Disorders • Orthopedics • Pain • Psychiatry

Preventive effects of active Protocol-Based Pharmacotherapy Management for delirium in general wards of emergency department (aPBPM trial): study protocol for a single-center, randomized controlled trial {1a}. (PubMed, Trials) - "This study will determine whether pharmacist-led proactive pharmacological intervention (Active PBPM) reduces the incidence of delirium in high-risk older patients in acute care settings. The findings may establish a new standard of care for the prevention of delirium in emergency medicine."

Journal • CNS Disorders • Cognitive Disorders • Geriatric Disorders • Insomnia • Mental Retardation • Psychiatry • Sleep Disorder

Doxepin Alone or Combined With Ramelteon Versus Placebo for Improving Sleep Quality After Primary Total Knee Arthroplasty (clinicaltrials.gov) - P4 | N=129 | Not yet recruiting | Sponsor: University of Washington

New P4 trial • Orthopedics • Pain

UHPLC-MS/MS Determination of Ramelteon in Rat Plasma and Its Altered Pharmacokinetics Under Simulated High Altitude: Relevance to High-Altitude Sleep Disorders. (PubMed, Biomed Chromatogr) - "Together with a proportional decrease in volume of distribution, these findings suggest that reduced first-pass metabolism and altered distribution collectively lead to an unchanged half-life. The elevated exposure indicates that a dose reduction may be warranted when ramelteon is used for high-altitude sleep disorders."

Journal • PK/PD data • Preclinical • CNS Disorders • Insomnia • Sleep Disorder • CYP1A2

A Review of Psychotropic Related Parasomnias and Their Management (APA 2026) - "These include antidepressant medications (e.g. amitriptyline, fluoxetine, citalopram, bupropion), antipsychotic medications (e.g. aripiprazole, clozapine, quetiapine, risperidone), hypnotics/sedatives (e.g. ramelteon, zolpidem), opioids (e.g. fentanyl, naloxone, tramadol), and nervous system agents (e.g. certain dopaminergic drugs, anesthetics and dementia medication). Different methods have been studied to minimize the effects of this disorder including promotion of good sleep hygiene, preventing sleep deprivation, and avoiding medications that trigger them. In this poster we aim to highlight the medications that can trigger parasomnias and their management."

Review • Alzheimer's Disease • CNS Disorders • Dementia • Mental Retardation • Movement Disorders • Narcolepsy • Obstructive Sleep Apnea • REM Sleep Behavior Disorder • Respiratory Diseases • Restless Legs Syndrome • Sleep Apnea • Sleep Disorder • Urinary Incontinence

Structural and Dynamics Insights into Melatonin Binding to MT1 Receptor. (PubMed, Chembiochem) - "Despite recent reports on X-ray free-electron laser and cryo-EM structures of MT1 receptor in complex with agonists, such as agomelatine, 2-phenylmelatonin and ramelteon, a detailed high-resolution description of the MT1 binding by melatonin under near to native (physiological) conditions is still missing. Combined with computational methodologies such as homology modeling, molecular docking and molecular dynamics simulations, this approach provides significant structural and dynamical insights into the interaction between MT1 receptor and melatonin. We found that MLT interacts, through hydrophobic interactions, with the orthosteric binding pocket enhancing receptor motions that in turn facilitate local rearrangements in the cytoplasmic portion of MT1."

Journal • Oncology

In Vitro Reaction Phenotyping and Projection of Drug Interactions Mediated by Cytochrome P450 Enzymes for Central Nervous System Drugs as Victims: Implications for Safety in Vulnerable Populations. (PubMed, Drug Metab Dispos) - "Reaction phenotyping with isoform-selective inhibitors quantified the fractional metabolic contribution (fm,cyp) of each enzyme, and inhibition parameters for fluvoxamine (CYP1A2), ticlopidine (CYP2B6), cinacalcet/paroxetine (CYP2D6), and ketoconazole (CYP3A4) were incorporated into a mechanistic static model using unbound hepatic inlet concentrations as surrogates for site of inhibition exposure...In contrast, CYP1A2 substrates showed high sensitivity to fm,cyp values exceeding 0.9, resulting in underprediction (eg, ramelteon-fluvoxamine, 66-fold) or overprediction (eg, tacrine)...Overprediction of select CYP3A4 interactions, such as lurasidone-ketoconazole, likely reflects underestimation of the fraction escaping intestinal metabolism...This study shows that human liver microsome-based reaction phenotyping reliably predicts CYP2B6, CYP2D6, and CYP3A4 interactions, whereas small deviations in fm,cyp for CYP1A2 substrates can cause substantial under- or overprediction...."

Journal • Preclinical • CYP1A2 • CYP3A4

Context-Dependent Temporal Changes in Hypnotics Involved in Suicide Attempts. (PubMed, Neuropsychopharmacol Rep) - "Hypnotics involved in suicide attempts changed in a context-dependent manner during the study period. The increase in non-GABAergic hypnotics was driven by DORAs, whereas reductions in BZ involvement were detectable only in overdose-related contexts. These findings suggest that evolving hypnotic availability may influence the profile of medications involved in self-poisoning."

Journal • Retrospective data

Time-dependent risk of falls associated with hypnotic use in hospitalized patients. (PubMed, Psychiatry Clin Neurosci) - "Fall risk associated with hypnotic use is not uniform throughout the day. Short-acting benzodiazepines were linked to evening and nighttime falls, while long-acting benzodiazepines increased morning fall risk. These findings highlighted the need to consider time-specific fall risks when prescribing hypnotics."

Journal

The Protective Effects of Ramelteon on Acute Intestinal Injury Caused by Experimentally Induced Endoplasmic Reticulum Stress. (PubMed, J Surg Res) - "Ram appears to possess the potential ability to ameliorate experimentally induced small bowel damage by suppressing ER stress."

Journal • Cardiovascular • Oncology • Reperfusion Injury • CASP3 • CASP8 • IL10 • TNFA