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

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)

Orexin antagonism attenuates pain-related and opioid-withdrawal-related negative affect without altering opioid analgesic efficacy (Neuroscience 2025) - "This study aims to determine if administration of the orexin antagonist suvorexant during opioid withdrawal impacts mechanical hypersensitivity, as well as pain- and withdrawal-related negative affect, and opioid analgesia. Involvement of the lateral hypothalamic peptide orexin in morphine dependence and withdrawal. Journal of Neuroscience, 23(8), 3106-3111."

Clinical • Late-breaking abstract • Addiction (Opioid and Alcohol) • CNS Disorders • Pain • Psychiatry • Substance Abuse • DERL1

Suvorexant ameliorates sleep-deprivation-associated acceleration of Alzheimer's-like pathologies in progressive transgenic mouse models of tauopathy (Neuroscience 2025) - "This data highlights both the potential benefits of suvorexant treatment in tauopathy models and provides insight into optimal treatment times based on age/pathological staging. Following the completion of this project, we aim to clarify the impact of SD on tau and other AD-like pathologies while potentially uncovering a novel therapeutic strategy to improve AD outcomes."

Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Frontotemporal Lobar Degeneration • Movement Disorders • Progressive Supranuclear Palsy • Proteinopathy • MAPT

The Effects of Orexin Antagonism on Fear Extinction in PTSD (clinicaltrials.gov) - P4 | N=40120 | Not yet recruiting | Sponsor: VA Office of Research and Development | Initiation date: Oct 2025 ➔ Jan 2026

Trial initiation date • CNS Disorders • Insomnia • Post-traumatic Stress Disorder • Sleep Disorder

SAILOR (SuvorexAnt for Insomnia and aLcohOl use disordeR): An open label pilot trial of suvorexant for the management of comorbid insomnia and alcohol use disorder (ANZCTR) - P2 | N=20 | Not yet recruiting | Sponsor: Eastern Health

New P2 trial • Addiction (Opioid and Alcohol) • CNS Disorders • Insomnia • Sleep Disorder

Activation of orexin neurons changes reward-based decision-making strategies. (PubMed, PNAS Nexus) - "These risky choice behaviors were canceled by suvorexant, an orexin receptor antagonist...The computational approach revealed that orexin/orexin neurons modulate the learning process and motivational value of rewards. Thus, our data suggest that orexin/orexin neurons affect the processing of reward-prediction error and alter strategy in reward-based decision-making."

Journal

Optimized synthesis of suvorexant and determination of eight residual solvents by headspace gas chromatography. (PubMed, RSC Adv) - "The optimized synthesis is characterized by cost-effectiveness, operational simplicity, and high yield, rendering it suitable for industrial-scale production. The established HS-GC method exhibits high specificity and sensitivity, making it a reliable approach for residual solvent quantification."

Journal

Targeting Altered Brain Activity During Sleep in a Mouse Model of Autism to Improve Behavioral Features During Wakefulness (AACAP 2025) - "The impacts of chronic administration of suvorexant on autism-related behaviors were examined in Shank3 mutant mice. Increased medium and high frequency power and synchrony are observed across many brain regions in Shank3 knockout mice during sleep, but not wake, states... Altered sleep is present in many NDDs. This preclinical study identified altered patterns of brain activity during sleep, but not wake, of a mouse model with high construct and face validity for a particular genetic neurodevelopmental syndrome. Chronic administration with a targeted sleep-promoting medication was effective in improving autism-related behavior, suggesting multiple benefits for individualized selection of sleep medications.ANI, ASD, R"

Preclinical • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Genetic Disorders • Psychiatry • Sleep Disorder

Innovative Pharmacological Trials Targeting Sleep Disturbances in Autism (AACAP 2025) - "Additionally, data from ongoing randomized trials will be shared examining the efficacy of 3 different hypnotics: diphenhydramine, suvorexant, and zolpidem. A comprehensive review of the current literature will be conducted and will focus on studies that used pharmacological agents used to target sleep disturbances. In light of our increased understanding of the neurotransmitters involved in sleep regulation, there is a lack of investigations assessing the biological effects of sleep agents in ASD. Our series of preliminary trials will shed the light on the effect of different hypnotics targeting different neurotransmitter systems on sleep physiology and quality. Data collection is ongoing, and more analyses will be completed when additional participants complete the investigations.ASD, SLP, PPC"

Autism Spectrum Disorder • CNS Disorders • Genetic Disorders • Sleep Disorder

Dual orexin receptor antagonists in insomnia: Toward a new therapeutic paradigm. (PubMed, Pharmacol Biochem Behav) - "Although three dual orexin receptor antagonists (DORAs), suvorexant, lemborexant, and daridorexant, are currently available and widely used to treat insomnia, the differences in their elimination half-lives are not sufficient. However, several challenges remain to be addressed in order to fully realize the clinical potential of DORAs. This review identifies four key challenges requiring resolution to advance their optimal use in clinical practice."

Journal • CNS Disorders • Insomnia • Sleep Disorder

Successful Methods for Switching from a Benzodiazepine Receptor Agonist to a Dual Orexin Receptor Antagonist for the Treatment of Insomnias. (PubMed, Clin Psychopharmacol Neurosci) - "We performed a secondary analysis of our prior retrospective study of the rate of DORA (suvorexant or lemborexant) continuance at 3 months after the introduction of these agents in 210 patients under long-term BZRA treatment. The analyses identified higher BZRA dose at baseline (Exp(B): 1.801, 95% CI: 1.008-3.216) as a predictor of both DORA continuation and BZRA tapering. These findings suggest that in efforts to switch a patient's insomnia medication to a DORA, the tapering of ultra-short/short-acting BZRAs can lead to the successful switch to a DORA among patients under high-dose BZRA treatment, whereas careful switching is necessary for patients under long-term BZRA treatment."

Journal • CNS Disorders • Insomnia • Sleep Disorder

Treatment of Disturbed Sleep in Progressive Supranuclear Palsy (PSP) (clinicaltrials.gov) - P4 | N=40 | Completed | Sponsor: University of California, San Francisco | Active, not recruiting ➔ Completed | N=60 ➔ 40

Enrollment change • Trial completion • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy • Sleep Disorder

Suvorexant and Sleep/Delirium in ICU Patients (clinicaltrials.gov) - P4 | N=100 | Completed | Sponsor: Beth Israel Deaconess Medical Center | Recruiting ➔ Completed

Trial completion • CNS Disorders • Critical care • Insomnia • Sleep Disorder

Catalytic Synergy Drives Triazole-Directed ortho-C(sp2)-H Functionalization. (PubMed, Org Lett) - "Leveraging catalyst-substrate synergy, diverse aryl triazoles─including the marketed neuropsychiatric drug suvorexant─were efficiently acylmethylated with sulfoxonium ylides. The resulting products served as versatile intermediates for further transformations, such as aerobic oxidation, triazole ring-opening, cyclization, and Wittig-type reaction, thus enabling rapid access to structurally diverse heterocycles and drug-like molecules. Mechanistic insights reveal that metal-triazole coordination governs the rate-determining step, with the metal identity decisively controlling both reactivity and selectivity."

Journal • Psychiatry

A Study of Suvorexant (MK-4305) for the Treatment of Insomnia Disorder in Participants With Opioid Use Disorder (MK-4305-098) (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: Merck Sharp & Dohme LLC | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Insomnia • Sleep Disorder • Substance Abuse

Efficacy and safety profiles of FDA-approved dual orexin receptor antagonists in depression: A systematic review of pre-clinical and clinical studies. (PubMed, J Psychiatr Res) - "DORAs show potential in improving sleep parameters in individuals with MDD. While their effects on depressive symptoms in this review are modest, further research is needed to assess long-term efficacy, safety, and their impact on depressive symptoms, as well as to explore potential combination therapies."

FDA event • Journal • Preclinical • Review • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • 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