doxepin / Generic mfg. - LARVOL DELTA

A pharmacometric framework for norepinephrine transporter occupancy and dose equivalence across psychotropic medications. (PubMed, J Psychopharmacol) - "These findings suggest that variability in NET engagement across psychotropic medications may not be fully captured by conventional class-based classifications. The proposed framework offers a mechanism-informed approach to comparative pharmacological analysis and introduces a conceptual noradrenergic activity index. This approach may be useful for hypothesis generation in future studies integrating pharmacokinetic-pharmacodynamic modeling with in vivo imaging and clinical outcomes."

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Antifungal and anti-biofilm activity of doxepin against Candida spp. mediated by oxidative stress and modulation of adhesion-related genes. (PubMed, Microb Pathog) - "Furthermore, it established stable interactions with the Als3 and Sap5 proteins, also promoting changes in the expression of virulence-related genes, such as als3, sap5, ece1, and hwp1. These findings indicate that DOX exhibits promising antifungal activity for the treatment of Candida infections, particularly highlighting its potential against biofilms."

Journal • Candidiasis • Infectious Disease • Metabolic Disorders

Prevalence of Psychotropic Drug Treatment Interventions in Patients Undergoing Metabolic and Bariatric Surgery: A Retrospective Study. (PubMed, Obes Surg) - "Although only a minority of patients required psychotropic drug treatment interventions, monitoring psychotropic drug treatment is essential for safe and effective treatment post-MBS. Greater attention is needed regarding altered drug exposure, and plasma concentration monitoring may help optimize psychotropic pharmacotherapy in these patients."

Journal • Retrospective data • CNS Disorders • Mental Retardation • Pain • Psychiatry

Doxepin Solution for Alleviation of Stubborn Breakthrough Pain Induced by Swallowing in Patients Receiving Radiotherapy for Nasopharyngeal Carcinoma (clinicaltrials.gov) - P=N/A | N=178 | Recruiting | Sponsor: Nanfang Hospital, Southern Medical University | Trial completion date: Feb 2026 ➔ Aug 2026 | Trial primary completion date: Feb 2026 ➔ Jul 2026

Trial completion date • Trial primary completion date • Head and Neck Cancer • Nasopharyngeal Carcinoma • Oncology • Pain • Solid Tumor

A SMART Approach to Evaluating the Benefits of Common Prescription and OTC Medications for Insomnia (clinicaltrials.gov) - P4 | N=1200 | Recruiting | Sponsor: University of Pennsylvania | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Insomnia • Sleep Disorder

Dual orexin receptor antagonism with lemborexant enhances microglial clearance of β-amyloid in mice. (PubMed, Mol Neurodegener) - "Lemborexant mitigates amyloid pathology by augmenting microglial phagocytic function, positioning DORAs as promising therapeutics that couple sleep promotion with beneficial microglial modulation."

Journal • Preclinical • Alzheimer's Disease • Anesthesia • CNS Disorders • Sleep Disorder • CD68

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

Pharmacologic Management of Insomnia in Adults. (PubMed, Prim Care) - "Evidence-based medication options include low-dose doxepin, melatonin receptor agonists, dual orexin receptor antagonists, and nonbenzodiazepine benzodiazepine receptor agonists. Ongoing follow-up is essential to monitor treatment response."

Journal • Review • CNS Disorders • Insomnia • Sleep Disorder • Sleep Wake Cycle Disorder

SMART Trial Comparing Commonly Prescribed and Over the Counter Medications for the Treatment of Insomnia in Adults (clinicaltrials.gov) - P4 | N=1200 | Not yet recruiting | Sponsor: University of Pennsylvania

New P4 trial • CNS Disorders • Insomnia • Sleep Disorder

Local therapeutic strategies for neurocutaneous dysesthesia: from capsaicin to cannabinoids. (PubMed, J Dermatolog Treat) - "The following local treatment options are described: capsaicin, calcineurin inhibitors, menthol, pramoxine/lidocaine/prilocaine, ambroxol, phenytoin, strontium, amitriptyline, doxepin, duloxetine, baclofen, gabapentin, cannabinoids, loperamide, naltrexone, clonidine, prazosin, acetylsalicylic acid, diclofenac, aprepitant, ketamine, calamine, polidocanol, and botulinum toxin type A. Local therapy offers a valuable and often well-tolerated first step in managing ND...Clinicians are advised to start with low concentrations, discuss off-label use, and monitor for side effects. Until robust guidelines are available, a cautious trial-and-error approach remains the cornerstone of management."

Journal • Review • Dermatology • Neuralgia • Pain • Pruritus

Serum Concentration-Dependent Inhibition of CYP2D6 by Bupropion and Doxepin: Implications for Venlafaxine and Risperidone Metabolism. (PubMed, Pharmacopsychiatry) - "These effects and a phenoconversion into poor metabolizer status were detectable at subtherapeutic hydroxybupropion and therapeutic antidepressant doxepin levels. Monitoring inhibitor and victim-drug concentrations may aid in managing clinically relevant CYP2D6-mediated interactions."

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PBPK modeling of the antidepressant doxepin incorporating CYP2D6 genotype for precision pharmacotherapy. (PubMed, Arch Pharm Res) - "The model reliably predicts genotype-dependent pharmacokinetic variability and provides a mechanistic basis for individualized dose optimization. This PBPK approach may serve as a valuable tool to support precision pharmacotherapy for doxepin, particularly in the context of antidepressant treatment."

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Enthalpy-Entropy Trade-Off Underlies Geometric Isomer Selectivity in Histamine H1 Receptor-Doxepin Interaction. (PubMed, ACS Med Chem Lett) - "These findings indicate that H1R distinguishes between E- and Z-isomers not only by affinity but also through distinct thermodynamic fingerprints. This study provides mechanistic insight into the enthalpy-entropy trade-off in GPCR-ligand interactions, highlighting the importance of conformational restriction and flexibility in designing ligands with optimized thermodynamic and functional properties."

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Real-world data on the abuse potential of medications for the treatment of insomnia: a disproportionality analysis of the FAERS database. (PubMed, Front Pharmacol) - "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 real-world abuse, misuse, overdose, and other safety risks for DORAs compared with the unscheduled drug trazodone and scheduled Z-drugs. This suggests that categorization of DORAs as Schedule IV drugs may overstate their abuse potential."

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

Clinical evidence for managing radiotherapy-induced oral mucositis and xerostomia in head and neck cancer patients: a review of Phase III-IV trials. (PubMed, Int J Oral Maxillofac Surg) - "For oral mucositis, effective pharmacological agents included palifermin, avasopasem manganese, doxepin, morphine mouthwash, and gabapentin, while non-pharmacological options such as low-level laser therapy, honey, and Aloe vera showed additional benefit in reducing severity and improving healing. In managing radiotherapy-induced xerostomia, pilocarpine, amifostine, and cevimeline significantly enhanced salivary function, with adaptive radiotherapy techniques offering protective effects on the salivary glands...Although several interventions demonstrated promising clinical efficacy, the heterogeneity in study design, outcome measures, and follow-up duration limits definitive conclusions. Therefore, customized, evidence-driven approaches informed by existing recommendations and developed data are crucial for enhancing outcomes and reducing the burden of therapy-induced toxicities in head and neck cancer patients."

Journal • P3 data • Review • Dental Disorders • Head and Neck Cancer • Mucositis • Oncology • Oral Cancer • Solid Tumor • Stomatitis • Xerostomia

Prefrontal cortex-extracellular vesicle RNAs coupling in alcohol use disorder: towards non-invasive biomarkers and targeted therapeutics. (PubMed, Artif Cells Nanomed Biotechnol) - "Computational drug repurposing identified loratadine, doxepin, citalopram and imipramine as promising therapeutic candidates targeting SERPINA3. Collectively, this work delineated PFC signature genes, proposed a EVs-supported brain-periphery molecular crosstalk, and provided translatable biomarkers and repurposable candidates for AUD precision medicine."

Biomarker • Journal • Addiction (Opioid and Alcohol) • IL17A • SERPINA3

Tricyclic Antidepressants as Prospective α-Synucleinopathy Fighters: Evidence of Protein Binding and Antiaggregation Activity. (PubMed, ACS Chem Neurosci) - "Here, we report the finding that clinically approved tricyclic antidepressants imipramine, amitriptyline, and doxepin bind directly to monomeric α-synuclein and inhibit its fibrillation, a key process in Parkinson's pathology...Moreover, simulations show that a single ligand molecule frequently engages in simultaneous salt-bridge and π-stacking interactions, unlike some previously studied α-synuclein binders. Our findings position tricyclic antidepressants as promising scaffolds for targeting α-synuclein and demonstrate the efficiency of molecular dynamics approaches for the description of interactions between small drug molecules and IDPs."

Journal • CNS Disorders • Movement Disorders • Parkinson's Disease

Dose-dependent pharmacological mechanisms within the Neuroscience-based Nomenclature: a new concept to facilitate neuroscience-based prescribing. (PubMed, Lancet Psychiatry) - "Using the Neuroscience-based Nomenclature (NbN) framework, which classifies drugs by pharmacology and modes of action, we identified ten agents demonstrating DDDP in a comprehensive expert-based consensus process: amisulpride, amitriptyline, aripiprazole, brexpiprazole, cariprazine, doxepin, mirtazapine, quetiapine, risperidone, and trazodone...Understanding these differences supports more rational prescribing (eg, increasing dopamine partial agonist doses beyond the optimal range might reduce efficacy). DDDP, within the NbN framework, offers a neuroscience-based approach to more precise psychopharmacology."

Journal • Review • NBN

Dutch Pharmacogenetics Working Group (DPWG) guideline for the gene-drug interaction between CYP2D6 and CYP2C19 and tricyclic antidepressants. (PubMed, Eur J Hum Genet) - "For CYP2D6 poor metabolisers (PM), dose reductions are advised for amitriptyline (reduction to 60% of the normal dose), clomipramine (reduction to 50% of the normal dose for the indication depression or in case of side effects at the normal dose for the other indications), doxepin (reduction to 40% of normal dose), imipramine (30% of the normal dose), and nortriptyline (40%)...The DPWG classifies CYP2D6 genotyping for all five TCAs and CYP2C19 genotyping for clomipramine in patients with anxiety disorders or OCD, and for imipramine as being "potentially beneficial". Genotyping prior to treatment can be considered on an individual patient basis."

Biomarker • Journal • CNS Disorders • Depression • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry • CYP2C19

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

Doxepin and Mirtazapine Use in Children and Adolescents With Symptoms of Insomnia - A Single-Center Retrospective Review. (PubMed, Pediatr Neurol) - "We found both doxepin and mirtazapine as effective and tolerable treatments options in improving subjective sleep onset and maintenance issues in children with insomnia."

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

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

Undiagnosed Delusional Infestation Leading to Severe Self-Inflicted Injuries: A Case Report. (PubMed, Case Rep Psychiatry) - "Treatment with low-dose risperidone and doxepin was initiated following empathic, nonconfrontational engagement...This case highlights the risk of severe self-injury in DI and underscores the need for timely psychiatric evaluation and a compassionate, collaborative approach. Reframing treatment goals to prioritize symptom relief over delusional challenge may enhance engagement and facilitate recovery."

Journal • Dermatology • Pruritus • Psychiatry • Thermal Injury

The use of antihistamine and antihistamine-like drugs for cancer-related pain: a narrative review. (PubMed, Support Care Cancer) - "Analysis of these studies demonstrated meaningful evidence that antihistamine and antihistamine-like drugs may offer some benefit for treating cancer-related pain."

Journal • Review • Mucositis • Oncology • Pain • Peripheral Neuropathic Pain • Stomatitis

Sleep-promoting effects and mechanisms of Bacillus coagulans IDCC 1201: evidence from pentobarbital-induced sleep and electroencephalography analysis in mice. (PubMed, Food Funct) - "Delta activity analysis indicated no adverse effects on sleep quality. These findings suggest that B. coagulans IDCC 1201 enhances sleep by modulating the GABAergic system and improving sleep architecture, highlighting its potential as a functional ingredient for sleep enhancement without the drawbacks of conventional sleep aids."

Journal • Preclinical • CNS Disorders • Infectious Disease