Belsomra (suvorexant) / Merck (MSD) - LARVOL DELTA

Sleep, wake, and signaling: Functional profiling of orexin agonists and antagonists using newly developed orexin β-arrestin 2 and miniGαq recruitment assays. (PubMed, Eur J Pharmacol) - "These assays were successfully applied to evaluate the pharmacological profiles of both agonists and antagonists, including the endogenous ligands orexin-A and -B, the clinically approved small molecule antagonists suvorexant and daridorexant, as well as EMPA (N-ethyl-2-[(6-methoxy-pyridin-3-yl)-(toluene-2-sulphonyl)-amino]-N-pyridin-3-ylmethyl-acetamide) and four other compounds described in literature to act at orexin receptors. The obtained receptor activation patterns and selectivity profiles were consistent with literature data, indicating the reliability and robustness of the assay systems. Overall, the newly developed assays expand the toolkit for orexin receptor research by allowing the characterization of both agonists and antagonists, thereby contributing to the functional characterization of potential new drug candidates for various pathological conditions."

Journal • CNS Disorders • Insomnia • Narcolepsy • Sleep Disorder • ARRB1

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

Suvorexant for alcohol use disorder and post-traumatic stress disorder: study protocol for a phase II randomized clinical trial. (PubMed, Trials) - P2 | "The combination of human laboratory modeling and real-world clinical outcomes provides a unique and synergistic set of data that can advance the development of suvorexant and identify its behavioral mechanisms of action. The recruitment of individuals with AUD and PTSD with sleep disturbances and who are intrinsically motivated to quit is a novel approach to screening pharmacotherapies by bridging the gap between experimental studies with non-treatment seekers and clinical trials with treatment-seeking individuals."

Clinical • Journal • P2 data • Addiction (Opioid and Alcohol) • CNS Disorders • Insomnia • Mood Disorders • Post-traumatic Stress Disorder • Sleep Disorder

Emerging neurobiological targets in psychiatric treatment. (PubMed, Eur Neuropsychopharmacol) - "Recent evidence suggests that sodium channel modulators, such as evenamide, may offer therapeutic benefits for treatment-resistant schizophrenia by stabilizing glutamatergic neurotransmission...Additionally, Sigma-1 receptor agonists, including Blarcamesine and Pridopidine, have shown neuroprotective and cognitive-enhancing properties, making them attractive candidates for psychiatric and neurodegenerative disorders. Orexin receptor antagonists, such as suvorexant and seltorexant, have potential in mood disorders and substance dependence, highlighting the broader therapeutic applications of targeting the orexinergic system...The identification of biomarkers for patient stratification will be critical in the hitherto elusive goal of developing precision medicine approaches. Targeted pharmacological interventions offer a path toward more effective, well-tolerated, and potentially individualized treatment options for patients with severe mental illness."

Journal • Review • Bipolar Disorder • CNS Disorders • Depression • Inflammation • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry • Schizophrenia

Evaluation of Suvorexant for Reduction of Brain Reactivity in Patients With Cannabis Use Disorder (Pilot Study) (clinicaltrials.gov) - P4 | N=20 | Recruiting | Sponsor: Massachusetts General Hospital | N=10 ➔ 20 | Trial completion date: Dec 2025 ➔ Jul 2026 | Trial primary completion date: Dec 2025 ➔ Jul 2026

Enrollment change • Trial completion date • Trial primary completion date • Substance Abuse

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

DISSECTING THE DYNAMIC RELATIONSHIP BETWEEN TAUOPATHY, SLEEP IMPAIRMENT AND AUTOPHAGIC-LYSOSOMAL DYSFUNCTION, AND IDENTIFICATION OF TRANSLATIONAL OPPORTUNITIES (ADPD 2026) - "Our study demonstrates progressive neuropathological and proteostatic alterations in tauopathy mouse models modeling changes observed in Alzheimer's disease (AD) and related dementias. Consistent with our previous findings, these models exhibited autophagic-lysosomal dysfunction, a key contributor to proteinopathy. Our results reveal a positive feedback loop wherein sleep disruption exacerbates tau accumulation, autophagic-lysosomal dysfunction, and neuroinflammation, accelerating disease progression."

Alzheimer's Disease • CNS Disorders • Dementia • Inflammation • Proteinopathy • Sleep Disorder • MAPT

Treatment of Disturbed Sleep in Progressive Supranuclear Palsy: a randomized, remote, double-blinded, 6-week cross-over design study protocol comparing zolpidem, suvorexant, and placebo. (PubMed, Trials) - "The study design aims to reduce participant and caregiver burden, while improving accessibility to such a study. Administering a remote clinical trial for a rare disease, however, creates unique issues that would otherwise be absent from in-person studies. Particularly, a symptom rather than disease-modifying trial is challenging to recruit for when potential disease-modifying therapeutics are available. Needing to coordinate with non-associated medical offices to attain medical records or prescriptions can cause frustrations for the potential participant, medical office, and study team. In recruitment, onboarding, and trial maintenance, this study design relies on consistent communication to support participant enrollment and satisfaction."

Journal • Alzheimer's Disease • CNS Disorders • Insomnia • Movement Disorders • Progressive Supranuclear Palsy • Rare Diseases • Sleep Disorder

Smartphone-Based Real-Time Assessment of Daytime Insomnia Symptoms With Suvorexant: A Randomized Clinical Trial. (PubMed, JAMA Netw Open) - P2 | "In this randomized clinical trial of older adults with insomnia, although traditional outcomes assessments detected no between-group differences, EMA was sensitive to detect effects of insomnia pharmacotherapy on daytime insomnia symptoms at various times of day, a critical gap in the literature. ClinicalTrials.gov Identifier: NCT05908526."

Clinical • Journal • CNS Disorders • Cognitive Disorders • Depression • Fatigue • Insomnia • Mood Disorders • Obstructive Sleep Apnea • Psychiatry • Respiratory Diseases • Sleep Disorder

Bajaj Healthcare Limited has secured regulatory approval from the Central Drugs Standard Control Organisation (CDSCO) on December 31, 2025, to conduct clinical trials and bioequivalence study for Suvorexant tablets (Scanx) - "The CDSCO approval enables Bajaj Healthcare to proceed with clinical testing and bioequivalence studies of Suvorexant tablets, a medication primarily used for treating sleep disorders....The approval indicates that the regulatory authority has reviewed and accepted the company's clinical trial protocol, manufacturing standards, and safety parameters for the proposed study."

New trial • Sleep Disorder

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

Evaluation of suvorexant effects on alcohol seeking and self-administration in baboons. (PubMed, Drug Alcohol Depend) - "Low dose suvorexant may acutely reduce drinking, but the magnitude of change may not be clinically meaningful. Higher doses of suvorexant may worsen heavy drinking. These data do not support suvorexant use to reduce alcohol intake during ongoing use."

Journal

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

Effectiveness and safety of dual orexin receptor antagonists for the prevention of delirium: A systematic review with meta-analysis and trial sequential analysis. (PubMed, Gen Hosp Psychiatry) - "DORAs, especially suvorexant showed promise for delirium prevention. However, strength of available evidence remains low due to small number of RCTs, risk of bias in several included studies, heterogeneity in observational data, and possible publication bias warranting cautious interpretation. In future, larger well-designed multinational trials are required to establish DORA use in delirium prevention."

Journal • Retrospective data • Review • CNS Disorders

Quantitative determination of suvorexant, lemborexant, and daridorexant in human plasma using a MonoTip C18 and gas chromatography-mass spectrometry. (PubMed, Forensic Toxicol) - "MonoTip C18 utilizes a reduced amount of solvent, thereby eliminating the need for evaporation-to-dryness steps. As a result, the entire procedure, encompassing SPE to GC-MS detection, can be completed within 40 min. This single protocol is applicable to all ORAs currently available in Japan and is suitable for both clinical and forensic toxicological applications."

Journal • CNS Disorders • Insomnia • Sleep Disorder

Bidirectional effects of orexin receptor antagonists on long-term potentiation in the hippocampus of wild type and Alzheimer's disease model mice. (PubMed, J Pharmacol Sci) - "In the present study, we evaluated the effects of chronic administration of dual orexin receptor antagonists, suvorexant (Suv) and lemborexant (Lem), on long-term potentiation (LTP) in the hippocampal CA1 region of wild-type (WT) and APPNL-G-F knock-in (APP-KI) mice. In contrast, in APP-KI mice, Suv moderately and Lem markedly reduced LTP. These findings suggest that orexin receptor antagonists bidirectionally modulate LTP in WT and AD model mice."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders

Fatal atomoxetine overdose in Japan: a forensic autopsy case report. (PubMed, Int J Legal Med) - "Cardiac blood screening, performed using a semi-quantitative analysis, detected 7-aminoflunitrazepam, 7-aminonitrazepam, allylisopropylacetylurea, aripiprazole, atomoxetine, bromazepam, and suvorexant. The atomoxetine and bromazepam concentrations were 23.2 and 0.71 µg/mL in femoral blood and 24.0 and 0.78 µg/mL in cardiac blood. In conclusion, the cause of death was primarily due to acute atomoxetine intoxication, with bromazepam excluded as a direct contributing factor."

Journal • ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Psychiatry

Current and novel dual orexin receptor antagonists for the treatment of insomnia: the emergence of vornorexant. (PubMed, Int J Neuropsychopharmacol) - "As an alternative target to generate novel hypnotics, the orexin system has recently gained much attention, and 3 dual orexin receptor antagonists (DORAs)-suvorexant, lemborexant, and daridorexant-were launched. Indeed, it has shown rapid sleep-promoting effects in patients with insomnia, maintaining its activity throughout the night but having a low incidence of next-day residual effects. In this review, we first provide an overview of the role of the orexin system in sleep/wake balance and then describe the profile of a newly developed DORA, vornorexant, from drug discovery to clinical results."

Journal • CNS Disorders • Insomnia • Sleep Disorder

Examining the Role of the Orexin System in Sleep and Stress in Persons With Opioid Use Disorder (clinicaltrials.gov) - P2 | N=138 | Completed | Sponsor: Johns Hopkins University | Recruiting ➔ Completed | N=200 ➔ 138 | Trial completion date: Aug 2026 ➔ Aug 2025 | Trial primary completion date: Aug 2026 ➔ Aug 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Sleep Disorder • Substance Abuse

Evidence of a functional interaction between orexin/corticotropin-releasing factor and orexin/dynorphin transmission in the infralimbic cortex following alcohol dependence: mediation of alcohol-seeking behavior (Neuroscience 2025) - "Following extinction training (12 sessions), the rats received an intra-IL microinfusion of the OX1/2 receptor antagonist suvorexant (15 μg/0.5 μl/side), the CRF1 receptor antagonist CP154,526 (0.6 μg/0.5 μl/side), the κ-opioid receptor antagonist nor-binaltorphimine (norBNI; 4 µg/0.5 µl/side), or a combination of suvorexant+CP154,526 or suvorexant+norBNI...Increases in Crhr1 and Hcrtr1 mRNA expression in the IL were found in alcohol-dependent rats only. These results demonstrate a functional interaction between OX/CRF/DYN receptor signaling in the IL in subjects with a history of alcohol dependence."

Addiction (Opioid and Alcohol) • CNS Disorders

Targeting the Orexin System to Alleviate Stress-Induced Dopamine Dysregulation (Neuroscience 2025) - "Additionally, we utilized in vivo electrophysiology and fiber photometry to demonstrate that suvorexant attenuates IC-evoked glutamatergic activity in the OFC. Finally, we examined how stress alters orexin release in the OFC.By identifying the circuit and molecular mechanisms through which stress alters dopamine system function, and by evaluating orexin receptor antagonism as a potential therapeutic strategy, this work aims to advance our understanding of stress-related neuropsychiatric disorders and inform novel treatments for PTSD, psychosis, and related conditions."

CNS Disorders • Mental Retardation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry

Suvorexant'S effect on sleep in female and male c57bl/6 mice during nicotine abstinence (Neuroscience 2025) - "Given the strong link between sleep disturbances and relapse, further research is warranted to evaluate suvorexant's potential as a therapeutic intervention for nicotine withdrawal-induced sleep disruptions. Targeting the orexin system may provide a novel approach to addressing both sleep and addiction-related challenges during nicotine cessation."

Preclinical • Addiction (Opioid and Alcohol) • CNS Disorders • Insomnia • Nicotine Addiction • Psychiatry • Sleep Disorder

Suvorexant helps protect against retinal neurovascular defects in db/db mice (Neuroscience 2025) - "Our findings suggest that suvorexant may be explored further as a potential treatment strategy for DR."

Preclinical • CNS Disorders • Insomnia • Sleep Disorder • IL1B • PLCG1 • TNFA

The Orexin System: A Target for the Treatment of Stress-Induced Sleep Alterations in a Rodent Model of PTSD (Neuroscience 2025) - "We have previously shown that Suvorexant, an FDA-approved dual OXR antagonist, reverses both stress-induced dopamine dysfunction and corresponding deficits in psychosis-like behaviors...This suggests that both OX1R and OX2R play a role in regulating REM sleep. Taken together, these data indicate that targeting the orexin system is relevant for the treatment of stress-induced sleep disruptions, particularly in PTSD patients."

Preclinical • CNS Disorders • Mental Retardation • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • Sleep Disorder

Orexin Receptor Antagonism for the Treatment of Alcohol Use Disorder and Stress-Related Drinking (clinicaltrials.gov) - P2 | N=250 | Recruiting | Sponsor: Ohio State University | Not yet recruiting ➔ Recruiting

Enrollment open • Addiction (Opioid and Alcohol)