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

Dual orexin receptor antagonist-assisted dose reduction of benzodiazepines and benzodiazepine receptor agonists: a mirror-image analysis of insurance claims data. (PubMed, J Clin Sleep Med) - "DORA treatment for at least six months may support BZ/BZRA dose reduction among long-term users, particularly in older patients."

Journal • Reimbursement • US reimbursement • CNS Disorders • Insomnia • Sleep Disorder

Dose-response meta-analysis of dual orexin receptor antagonists on sleep parameters and implications for orexin-mediated arousal. (PubMed, Sleep Med) - "DORAs produce dose-related improvements in insomnia sleep-related outcomes, with most effects plateauing within therapeutic ranges. This pattern is consistent with a pharmacodynamic ceiling whereby sufficient attenuation of orexin-mediated arousal is achieved within approved dose ranges, limiting the value of further dose escalation. These findings do not support supratherapeutic dosing and suggest that clinical response may be better judged after repeated administration."

Journal • Retrospective data • Review • CNS Disorders • Insomnia • Sleep Disorder

Managing Sleep in Bipolar Disorder: An Overview of Pharmacological and Non-Pharmacological Interventions. (PubMed, Bipolar Disord) - "Sleep-focused interventions, especially behavioral strategies such as CBTI-BD, appear effective and well tolerated for managing sleep disturbances in BD, primarily in euthymic and interepisode samples where they have been tested. Pharmacological interventions show more variable effects and require careful attention to tolerability and clinical stability. Because each intervention was evaluated in a single clinical phase, the available evidence cannot determine whether clinical phase or chronotype moderates treatment response; trials designed to detect such moderation are needed before individualized, phase-specific recommendations can be made."

Journal • Review • Bipolar Disorder • CNS Disorders • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder

Sleep-modulating pharmacological interventions for delirium prevention: a systematic review and a network meta-analysis of randomized controlled trials. (PubMed, Sleep Med Rev) - "Evidence from suvorexant trials was also associated with a lower delirium risk (RR = 0.51, 95% CI: 0.27-0.95), whereas midazolam-based benzodiazepine evidence did not demonstrate a statistically significant reduction in delirium risk (RR = 1.64, 95% CI: 0.81-3.31). Melatonin-based interventions and suvorexant were associated with lower delirium incidence; however, evidence directly comparing different active interventions remains limited, and findings should be interpreted cautiously given the agent-specific evidence base. Further direct comparative trials are needed to clarify the effectiveness and safety of sleep-modulating pharmacological interventions for delirium prevention."

Journal • Retrospective data • Review • CNS Disorders • Psychiatry

Plasma and breast milk pharmacokinetics of suvorexant in healthy lactating women. (PubMed, Br J Clin Pharmacol) - "Following a 20-mg dose in healthy lactating women, suvorexant exposure in breast milk was markedly lower than plasma exposure. The mean estimated theoretical infant daily dose was less than 1% of the maternal dose."

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

Orexin Signaling, Glymphatic Clearance, and Preclinical Alzheimer's Disease: A Scoping Review and Hypothesis-Generating Conceptual Framework. (PubMed, Curr Alzheimer Res) - "Preclinical findings remain preliminary and lack human validation. This review maps existing biomarker literature to generate mechanistic hypotheses; no integrative risk model, threshold combination, or stratification tool is proposed. Mechanistic proof-of-concept studies must precede any consideration of larger trials or translational application."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Dementia • Insomnia • Sleep Disorder • APOE • Aβ42

Suvorexant Prescription-Record Rates After a Palliative Care Pocket Manual Revision: A Single-Centre Interrupted Time Series Study. (PubMed, J Pain Palliat Care Pharmacother) - "This local pharmacotherapy guidance revision coincided mainly with a secondary outpatient prescribing signal. Causality, clinical utility, and patient outcomes cannot be inferred."

Journal • CNS Disorders • Insomnia • Palliative care • Sleep Disorder

Long-term use of dual orexin receptor antagonists for the treatment of insomnia: a systematic review and meta-analysis. (PubMed, Arq Neuropsiquiatr) - "Adults with primary insomnia treated with DORAs (suvorexant, lemborexant, or daridorexant) approved by the United States Food and Drug Administration (FDA) for ≥ 6 months were included. Higher doses may be less well tolerated. Additional long-term randomized trials are needed to better define the efficacy and safety of DORAs in clinical practice."

Clinical • Journal • Retrospective data • Review • CNS Disorders • Insomnia • Sleep Disorder

Neuroprotective Effects of AnMei Decoction on Hypothalamic Neuronal Injury and Circadian Rhythm Dysregulation in Murine Models of Insomnia. (PubMed, J Ethnopharmacol) - "Our findings suggest that AMD exerts significant sleep-stabilizing effects, which may involve the modulation of the hypothalamic orexin system and core circadian clock genes. These results provide pharmacological evidence supporting the traditional use of AMD against insomnia and highlight its therapeutic potential as a candidate agent for addressing anxiety and cognitive impairments associated with sleep disorders."

Journal • Preclinical • CNS Disorders • Cognitive Disorders • Insomnia • Psychiatry • Sleep Disorder • ARNTL • BMAL1 • CRY1 • PER1

A Narrative Review: Suvorexant's Role in Sleep Deprivation and Neurodegenerative Disease. (PubMed, Curr Neuropharmacol) - "Long-term clinical trials are necessary, however, to prove its effectiveness in humans, especially in populations at risk for sleep disorders and early neurodegenerative alterations. Suvorexant could be a novel approach to slow cognitive decline and improve quality of life in patients with AD, PD, and related diseases, highlighting the vital interplay between sleep and brain health."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • Movement Disorders • Parkinson's Disease • Sleep Disorder

Suvorexant as an Adjunct to Buprenorphine in Persons Who Use Fentanyl (clinicaltrials.gov) - P2 | N=76 | Completed | Sponsor: Johns Hopkins University | Recruiting ➔ Completed | N=120 ➔ 76

Enrollment change • Trial completion • Substance Abuse

Dual hypocretin receptor antagonism reduces oxycodone seeking and attenuates aberrant dopamine transporter function during abstinence. (PubMed, Neuropharmacology) - "Treatment with suvorexant 24 h prior to a cue-induced seeking test significantly reduced oxycodone seeking and attenuated aberrant dopamine uptake. These findings suggest that targeting hypocretin receptors could be a promising strategy for reducing opioid craving and associated neuroadaptations, thus lowering the risk of relapse."

Journal • Substance Abuse

In Silico to In Cerebro-Development of the Orexin Receptor Antagonist "Photorexant" for Photomodulation In Vitro and in Mouse Brains. (PubMed, Angew Chem Int Ed Engl) - "We implemented a prospective structure-based design approach, generating azobenzene-containing derivatives of the FDA-approved dual orexin receptor antagonist suvorexant with a computational workflow that featured a novel fragmentation and azobenzene-fusion strategy...A newly optimized assay protocol for the characterization of photoswitchable GPCR antagonists demonstrated dynamic, reversible photomodulation of orexin receptors by photorexant in vitro. Electrophysiological studies in hypothalamic and locus coeruleus neurons in mice demonstrated photomodulation of its antagonistic properties in vivo, positioning photorexant as an excellent tool for further investigation of orexin signaling."

Journal • Preclinical • CNS Disorders • Mental Retardation • Psychiatry • ARRB1

Efficacy of Suvorexant on Post-operative Sleep Disturbance (clinicaltrials.gov) - P4 | N=100 | Completed | Sponsor: Columbia University | Recruiting ➔ Completed | Trial completion date: May 2025 ➔ Dec 2025 | Trial primary completion date: May 2025 ➔ Nov 2025

Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Insomnia • Sleep Disorder

Targeting Orexin to Treat Nicotine Dependence (clinicaltrials.gov) - P1 | N=45 | Active, not recruiting | Sponsor: Mclean Hospital | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2024 ➔ Dec 2026 | Trial primary completion date: Dec 2024 ➔ Jul 2026

Enrollment closed • Trial completion date • Trial primary completion date • Nicotine Addiction

Dual orexin receptor antagonists for preventing delirium in hospitalized older adults: protocol for a randomized-trial systematic review and meta-analysis. (PubMed, Syst Rev) - "This protocol addresses a focused clinical question while explicitly separating formal review inclusion from eligibility for the primary quantitative synthesis. This distinction is intended to prevent clinically indirect evidence, including mixed-age data, post-delirium treatment, unbalanced combination regimens, or unvalidated delirium ascertainment, from being interpreted as practice-changing evidence for prevention in hospitalized older adults."

Journal • Retrospective data • Anesthesia • CNS Disorders • Cognitive Disorders • Psychiatry

Suvorexant 3 - PE-PC (clinicaltrials.gov) - P4 | N=142 | Not yet recruiting | Sponsor: Northern California Institute of Research and Education

New P4 trial • CNS Disorders • Insomnia • Post-traumatic Stress Disorder • Sleep Disorder • Vascular Neurology

A Scoping Review of Orexin Antagonists in Post-Traumatic Stress Disorder: Modulating Sleep, Stress, and Fear Circuits. (PubMed, Mil Med) - "The reviewed evidence supports orexin receptor antagonism-particularly via dual antagonists like suvorexant-as a promising therapeutic approach for PTSD, with benefits across numerous domains: fear extinction, sleep regulation, hyperarousal, and cellular stress resilience. These findings suggest that orexinergic overactivation contributes to PTSD pathophysiology and that DORAs may offer an advantage over traditional sedatives by enhancing REM sleep and modulating stress signaling. Limitations include a predominance of preclinical data and heterogeneity in experimental models. Nonetheless, these studies provide a mechanistic foundation for larger clinical trials, particularly in patients with treatment-resistant PTSD or prominent sleep disturbance. Future research should explore receptor-specific roles, optimal timing of intervention, and biomarkers predictive of treatment response."

Journal • CNS Disorders • Insomnia • Metabolic Disorders • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • Sleep Disorder

Evaluation of Suvorexant for Reduction of Brain Reactivity in Patients With Cannabis Use Disorder (Pilot Study) (clinicaltrials.gov) - P4 | N=20 | Completed | Sponsor: Massachusetts General Hospital | Recruiting ➔ Completed

Trial completion • Substance Abuse

SToP-AD: Sleep Trial to Prevent Alzheimer's Disease (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Washington University School of Medicine | N=200 ➔ 120

Enrollment change • Alzheimer's Disease • CNS Disorders

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

Suvorexant for Treatment of AUD and PTSD (clinicaltrials.gov) - P2 | N=76 | Recruiting | Sponsor: Pharmacotherapies for Alcohol and Substance Use Disorders Alliance | Not yet recruiting ➔ Recruiting | Trial completion date: Jun 2026 ➔ Mar 2027 | Trial primary completion date: Jun 2026 ➔ Mar 2027

Enrollment open • Trial completion date • Trial primary completion date • Addiction (Opioid and Alcohol) • CNS Disorders • Insomnia • Mood Disorders • Post-traumatic Stress Disorder • Sleep Disorder

Measuring Acute Drug Demand in Humans (clinicaltrials.gov) - P1 | N=75 | Recruiting | Sponsor: University of Maryland, Baltimore | Suspended ➔ Recruiting

Enrollment open • Addiction (Opioid and Alcohol) • Substance Abuse

Role of suvorexant in Alzheimer's disease: Targeting sleep, orexin signaling, and disease pathophysiology. (PubMed, J Alzheimers Dis) - "We also emphasize future research directions such as cognitive outcomes over extended periods, potential optimal dosing, and combinatory strategies with lifestyle and/or medication therapies. This review will discuss the current evidence regarding the therapeutic effects of suvorexant and orexin signaling in AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Inflammation • Sleep Disorder

Effect of the orexin receptor antagonist, suvorexant, on sleep architecture in the early postoperative period following cardiac surgery: a randomized controlled trial. (PubMed, Crit Care) - P4 | "Among patients recovering in the ICU who underwent cardiac surgery with cardiopulmonary bypass, the suvorexant treatment did not affect wakefulness after sleep onset or post-operative delirium."

Journal • Cardiovascular • CNS Disorders • Critical care • Insomnia • Sleep Disorder