nortriptyline / Generic mfg. - LARVOL DELTA

Imipramine solubility-pH profiles: self-aggregation vs. common-ion effect. (PubMed, ADMET DMPK) - "The pH-dependent solubility of imipramine, a tricyclic antidepressant, and its hydrochloride salt was investigated in phosphate buffers and chloride-containing aqueous media using the pH-ramp shake-flask method. These findings, along with our previous solubility studies of desipramine and nortriptyline, suggest that even subtle structural variations can lead to significant differences in the aqueous media behaviour of tricyclic antidepressants. This type of information can be valuable in the early stages of drug discovery, in formulation optimization experiments, as well as in in vitro and in vivo studies."

Journal

The effect of nortriptyline and its combination with mometasone on secretion of IL-6 and IL-8 by stimulated blood mononuclear cells in vitro. (PubMed, Biomed Khim) - "This was evidenced by a decrease in IL-6 and IL-8 secretion compared to the use of mometasone alone. The study demonstrates the ability of nortriptyline to suppress the secretion of proinflammatory cytokines by blood cells, which is selective and dependent on the type of immune response."

Journal • Preclinical • Inflammation • CXCL8 • IL12A • IL1B • IL2 • IL23A • IL33 • IL6 • TSLP

Comparative Efficacy of Antidepressants for Post-stroke Depression: Bayesian Network Meta-analysis of Randomized Controlled Trials (AAN 2026) - "In a separate three-treatment analysis for HDS at 3 months, nortriptyline was most efficacious (SUCRA=0.084), followed by placebo and fluoxetine. Citalopram and sertraline generally ranked lower across outcomes. Duloxetine and escitalopram demonstrate superior efficacy for both depressive and anxiety symptoms in PSD in the short-to-medium term, while nortriptyline appears highly effective for depression at 3 months. These findings can guide clinical decision-making for antidepressant selection in PSD management."

Retrospective data • Cardiovascular • CNS Disorders • Depression • Mood Disorders • Psychiatry

Synergistic antibacterial and anti-inflammatory potentials of dual-loaded self-healing hydrogel for methicillin-resistant Staphylococcus aureus-infected wound healing. (PubMed, J Pharm Anal) - "Herein, nortriptyline, a novel United States Food and Drug Administration (FDA)-approved tricyclic antidepressant was uncovered to effectively potentiate bactericidal activities of β-lactam antibiotics against methicillin-resistant Staphylococcus aureus (MRSA)...OHA-PLL@AN therapy significantly attenuated the inflammatory response, concurrently promoting angiogenesis and accelerating the cutaneous wounds healing. Collectively, these findings underscore the dual drug-loaded self-healing hydrogel OHA-PLL@AN with anti-infection and anti-inflammatory properties as a novel therapeutic strategy for drug-resistant bacterial infected wounds therapy."

Journal • Infectious Disease • Inflammation

Synergistic Effects of Levodopa, Benserazide, and Nortriptyline on Behavioral Impairments and Brain Pathology in an Experimental Rat Model of Parkinson's Disease. (PubMed, Neurol Res Int) - "Nortriptyline at 10 mg/kg offers a promising adjunctive therapy for alleviating both motor and nonmotor symptoms of PD. However, higher doses may induce anxiogenic effects, suggesting the need for careful dose optimization."

Journal • Preclinical • CNS Disorders • Depression • Movement Disorders • Parkinson's Disease • Psychiatry

Tailored treatment of functional dyspepsia with nortriptyline: a multi-center, double-blind, placebo-controlled trial. (PubMed, Clin Gastroenterol Hepatol) - P3 | "Nortriptyline was not more effective than placebo in reducing FD symptoms in participants pre-selected based on CYP2D6 genotype, although a biological effect of nortriptyline could not be ruled out. However, effects related to participants' belief appeared to be stronger; Clinicaltrials.gov number, NCT03652571."

Journal • CNS Disorders • Dyspepsia • Gastrointestinal Disorder

Nitrosamine Drug Substance-Related Impurities cause DNA methylation adducts in vitro and in primary hepatocytes upon Cytochrome P450-dependend metabolic activation. (PubMed, Regul Toxicol Pharmacol) - "Given their regulatory relevance, this study assessed the genotoxic potential of three NDSRIs -N-nitrosobetahistine (NBH), N-nitrosofluoxetine (NFluo), and N-nitrosonortriptyline (NNT) -compared to NDMA. Furthermore, all NDSRIs showed cytotoxicity after 24 h, whereas no cytotoxic effect was observed for NDMA. Taken together, our study provided evidence that the three NDSRIs are genotoxic in primary rat hepatocytes, which warrants further investigation with regard to their mutagenic potential."

Journal • Preclinical

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

Middle meningeal artery lidocaine infusion for refractory migraine: First case report in Portugal (EHF-EHC 2025) - "Various pharmacologic classes were tried without benefit: antihypertensives and calcium channel blockers (propranolol, candesartan, flunarizine), antiepileptics (valproic acid, topiramate, oxcarbazepine), antidepressants (amitriptyline, nortriptyline, venlafaxine, fluvoxamine, sertraline, clomipramine), other preventives (prednisolone, oxitriptan, melatonin), cycles of botulinum toxin (PREEMPT protocol), monoclonal antibodies (galcanezumab, fremanezumab, erenumab), and atogepant. At the time of the procedure, the patient was on eptinezumab 100 mg and botulinum toxin every three months but continued to have daily headaches, with severe intensity and reliance on eletriptan for acute relief... MMA lidocaine infusion has been described in few cases, and this is, to our knowledge, the first reported in Portugal. It constitutes an invasive therapeutic approach that should be considered only as a rescue option for carefully selected patients with severely refractory migraine...."

Case report • Clinical • Anorexia • CNS Disorders • Migraine • Pain

Migraine-based subtyping of Ménière's disease: Implications for personalized diagnosis and therapy (EHF-EHC 2025) - "These patients may respond differently to conventional MD therapies but show potential benefit from migraine prophylactic measures, such as lifestyle modifications and nortriptyline The identification of a migraineassociated subtype in Meniere"s disease holds significant clinical importance, highlighting shared neurovascular and inflammatory pathways between the two disorders... The identification of a migraineassociated subtype in Meniere"s disease holds significant clinical importance, highlighting shared neurovascular and inflammatory pathways between the two disorders. This subtyping approach facilitates more personalized management strategies, improves prognostic accuracy, and guides targeted therapeutic interventions. Future research integrating multimodal biomarkers is essential to validate and refine this classification, ultimately advancing toward precision medicine in MD care Fig."

CNS Disorders • Immunology • Migraine • Otorhinolaryngology • Pain • Vertigo • IL1B

TPS-Select: An Artificial Intelligence Driven Approach to Optimize Patient Selection for a Transitional Pain Service (clinicaltrials.gov) - P3 | N=126 | Not yet recruiting | Sponsor: University of California, San Francisco

New P3 trial • Pain

Low-dose cannabidiol increases plasma concentrations of amitriptyline: A clinical drug-drug interaction study. (PubMed, Br J Clin Pharmacol) - "A single dose of 30 mg CBD significantly influenced the metabolism of amitriptyline in healthy volunteers. In patients, CBD-induced drug interactions may be more pronounced in chronic dosing and dependent upon prandial status."

Journal • Pain

Periosteal Osteosarcoma: Emerging Clinical Concepts, Evolving Treatment Options: A Narrative Review. (PubMed, Curr Pain Headache Rep) - "Adjuvant drugs can reduce inflammation and neuropathic pain, including corticosteroids, gabapentinoid agents such as gabapentin or pregabalin, lidocaine patches, tricyclic antidepressants such as amitriptyline, nortriptyline, and desipramine, or selective serotonin-norepinephrine reuptake inhibitors such as duloxetine and venlafaxine. The present investigation aims to synthesize currently available data on periosteal osteosarcomas, including common clinical, histologic, and radiographic presentations. In addition, this review aims to further examine the potential for biomarkers and provide recommendations for treatment and future research direction."

Journal • Review • Musculoskeletal Pain • Neuralgia • Oncology • Osteosarcoma • Pain • Sarcoma • Solid Tumor • TP53

Impact of Valproic Acid on Serum Nortriptyline Levels (ASHP 2025) - No abstract available

Management of Small Fiber Neuropathy: A Clinical Perspective. (PubMed, Muscle Nerve) - "First-line medications include amitriptyline, nortriptyline, gabapentin, and pregabalin. Second-line treatments can include serotonin-norepinephrine reuptake inhibitors and selective serotonin reuptake inhibitors such as duloxetine and venlafaxine, as well as lidocaine patches and capsaicin."

Journal • Diabetes • Immunology • Infectious Disease • Metabolic Disorders • Neuralgia • Pain

Dramatic Response to Lidocaine Infusion Therapy for Chronic Generalized Pain Secondary to Multiple Large Keloids. (PubMed, Cureus) - "Conventional treatments, including surgical excision with intralesional corticosteroids, duloxetine, meloxicam, amitriptyline, and acupuncture, provided only transient relief. Moderate pain relief was achieved with pregabalin, nortriptyline, topical lidocaine, and medical marijuana, resulting in a visual analog scale (VAS) score of 8/10. The subsequent addition of intravenous (IV) lidocaine infusions (5 mg/kg administered over one hour) produced significant pain reduction (VAS 3/10) and notable improvements in quality of life and functional capacity, enabling her to maintain employment. The interval between infusions was later extended to every four months while maintaining pain relief, without neuroexcitatory or cardiac complications. This case suggests that periodic IV lidocaine infusions may offer a safe and effective therapeutic option for sustained analgesia in patients with chronic keloid-related pain."

Journal • Fibrosis • Infectious Disease • Mood Disorders • Musculoskeletal Pain • Neuralgia • Pain • Varicella Zoster

Use of oral neuromodulators in chronic pelvic painNumber 8 - 2025. (PubMed, Rev Bras Ginecol Obstet) - "•Pregabalin is the medication with the best pharmacokinetic profile; nortriptyline has the best adverse effects profile; duloxetine is the most widely used and has the lowest risks; and venlafaxine should be used as a second-line inhibitor. •Although the drug classes can be combined to reduce the total doses and minimize side effects, maximizing the analgesic effect, monotherapies are recommended as the first line to avoid polypharmacy."

Journal • Review • Gynecology • Musculoskeletal Pain • Neuralgia • Pain

Nortriptyline-targeted siRNA-loaded liposomes: Design, affinity, biodistribution, and bioactivity in a murine Herpes Simplex Virus 1 corneal infection model. (PubMed, Eur J Pharm Sci) - "In the corneal limbus, targeted liposomes produced a significant reduction in viral load, whereas in the contralateral trigeminal ganglia, they significantly reduced viral load with a pronounced trend toward decreased ICP0 expression. These results demonstrate the feasibility of using NTP-mediated targeting ligand and support the potential of this delivery platform for treating latent HSV1, warranting further optimization for improved therapeutic efficacy."

Journal • Preclinical • Herpes Simplex • Infectious Disease • Keratitis • Ocular Infections • Ocular Inflammation • Ophthalmology

Determination of Nitrosamine Drug Substance-Related Impurities Derived from Nortriptyline and Sertraline Using LC-MS/MS: A Comparative Evaluation of Chromatographic Separation and Pharmaceutical Application. (PubMed, Pharmaceuticals (Basel)) - "The application of this method to commercial products subjected to accelerated stress testing revealed NNORT formation in NORT products with an average concentration of 190 ng/g, as well as NSERT formation in SERT products resulted in an average concentration of 172 ng/g. This validated method provides a reliable tool for routine quality control, thereby enabling pharmaceutical manufacturers and regulatory agencies to ensure safety and compliance with widely used antidepressant medications."

Journal

Preclinical Evidence for Nortriptyline as a Precision Therapeutic for SYNGAP1-Related Neurodevelopmental Disorder (AES 2025) - "These preclinical findings indicate that nortriptyline shows promise as a precision therapeutic for SYNGAP1 NDD by correcting SYNGAP1 haploinsufficiency. Our results also indicate that benefit with nortriptyline may be possible when epilepsy and cognitive/behavioral deficits are already present; disease phenotypes may be at least partially reversible. This work underscores the utility of high-throughput drug screening based on transcriptomic profiles, to identify treatments for genetic disorders caused by haploinsufficiency."

Neurodevelopmental • Preclinical • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Epilepsy • Genetic Disorders • Mental Retardation • Psychiatry

Malignant Atrophic Papulosis: A Manageable Death Sentence? (ASH 2024) - "Her ANA titer was positive.The patient was initially started on hydroxychloroquine, with improvement in her joint pains...However, she continued to develop skin lesions and migraines, for which she was prescribed nortriptyline.Three years after her initial onset of symptoms, she presented acutely to her local hospital with two months of worsening abdominal pain...Antiplatelet drugs such as aspirin, clopidogrel and pentoxifylline have been known to help but failed to halt the disease progression in this case...In our case, the patient noted significant improvement in her abdominal pain and overall condition after the very first infusion of eculizumab. This case emphasizes the importance of further research to manage patients with the malignant/systemic form of this disease and understand how it progresses. Further work should be done to assess the benefits of expedited use of eculizimab, and to identify the benefits of screening for systemic disease in patients with..."

CNS Disorders • Gastrointestinal Disorder • Infectious Disease • Migraine • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Thrombosis

Cognitive changes in older adults receiving pharmacotherapy for treatment-resistant depression: a secondary analysis of the OPTIMUM randomised controlled trial. (PubMed, Lancet Healthy Longev) - P4 | "Overall, global cognitive functioning did not differ between treatments. Aripiprazole augmentation and switch to nortriptyline might have some modest advantages in inhibitory control compared with bupropion or lithium augmentation."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Peripheral Neuropathy: A Review. (PubMed, JAMA) - "Other causes of neuropathy include hereditary causes, such as Charcot-Marie-Tooth disease, toxic neuropathy from medications (chemotherapies [eg, cisplatin, paclitaxel, vincristine], amiodarone, or HIV nucleotide reverse transcriptase inhibitors [eg, stavudine, zalcitabine]); alcohol; vitamin deficiencies such as vitamin B12; and monoclonal gammopathies...First-line medications for neuropathic pain are the α2-δ calcium channel subunit ligands, such as gabapentin and pregabalin; serotonin norepinephrine reuptake inhibitors, such as duloxetine and venlafaxine; and tricyclic antidepressants, such as amitryptyline and nortriptyline...Diabetes is the most common cause of peripheral neuropathy in Western countries. First-line therapies for neuropathic pain include gabapentin, pregabalin, duloxetine, and amitriptyline."

Journal • Addiction (Opioid and Alcohol) • Diabetes • Diabetic Neuropathy • Genetic Disorders • Human Immunodeficiency Virus • Hypotension • Infectious Disease • Metabolic Disorders • Monoclonal Gammopathy • Neuralgia • Pain • Peripheral Neuropathic Pain

Effectiveness of Escitalopram and Nortriptyline on Depressive Symptoms in Parkinson's disease: the ADepT-PD RCT pilot. (PubMed, Health Technol Assess) - P3 | "57. See the NIHR Funding and Awards website for further award information."

Journal • CNS Disorders • Depression • Hepatology • Movement Disorders • Parkinson's Disease • Psychiatry

The Investigation of the Mechanism of Action of Chloroquine Retinopathy: By prevention of lysosomal membrane permeabilization (LMP) (Neuroscience 2025) - "A total of three candidate protective drugs were selected, amiodarone, nortriptyline and desipramine, amiodarone was selected as the most effective against cell death measured by LDH release (amiodarone: 27.65 ± 5.56%, nortriptyline: 64.30 ± 7.73%, desipramine: 67.30 ± 9.36%). The identified compounds represent promising candidates for adjunct therapies to prevent vision loss in patients requiring long-term CQ treatment. Further validation in animal models and clinical studies is warranted to translate these protective effects into clinical practice."

CNS Disorders • CTSD