trazodone ER / Generic mfg. - LARVOL DELTA

THE TAUOPATHY-RELATED PERK HAPLOTYPE B IN NOVEL ISOGENIC IPSC LINES AND MOUSE MODEL (ADPD 2026) - " We observed that the neuronal culture from PERK B/B mounted a higher response to the ER stressor thapsigargin (TG) and another ER stressor tunicamycin (TM), as shown by CHOP, ATF4 and p-eIF2alpha expression...NDC1 PERK B/B requires higher dose of trazodone to reduce the CHOP expression compared to NDC1 PERK A/A. The PERK Haplotype B alters the normal function compared to its isogenic control PERK Haplotype A. The PERK Haplotype B is less responsive to the ISR inhibitor and required a higher dose compared to Haplotype A. These results suggest that the PERK Haplotype may affect response to ISR inhibitors and may have implications for therapeutic development of ISR inhibitors."

Preclinical • CNS Disorders • Movement Disorders • Progressive Supranuclear Palsy • ATF4

DIVERSE ALZHEIMER'S DISEASE GENETICS AND MULTI-OMICS DATA FUEL TARGET AND DRUG DISCOVERY: A CASE STUDY FROM THE NIH/NIA AI/ML CONSORTIUM (ADPD 2026) - "We demonstrated that EC5026 (a first-in-class, picomolar EPHX2 inhibitor) improves cognition in a 5xFAD mouse model. Combining genetics and multi-omics data via AI/ML technologies identifies ancestry-specific therapeutic targets and medicines for Alzheimer's disease."

Case study • Clinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • p-tau181

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

Management of insomnia symptoms in depressed patients treated with agomelatine, mirtazapine and trazodone: A systematic review and meta-analysis. (PubMed, J Affect Disord) - "All three medications significantly enhance subjective sleep perception and alleviate depressive symptoms. However, agomelatine may lack a definitive effect on improving objective sleep parameters in depressed patients. Future studies should involve larger, high-quality trials with unified methodologies to strengthen the reliability of conclusions."

Journal • Retrospective data • Review • Anesthesia • CNS Disorders • Depression • Insomnia • Mood Disorders • Pain • Psychiatry • Sleep Disorder

Expert consensus on the use of trazodone in patients with major depressive disorder: Results from a European Delphi panel. (PubMed, Eur Psychiatry) - No abstract available

Journal • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Trazodone and the Risk of Serious Adverse Events (clinicaltrials.gov) - P=N/A | N=31459 | Completed | Sponsor: London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's

Adverse events • New trial • Serious adverse event • Chronic Kidney Disease • Nephrology • Renal Disease

Prediction of 12-Week Remission in Patients With Depressive Disorder Using Reasoning-Based Large Language Models: Model Development and Validation Study. (PubMed, JMIR Ment Health) - "We analyzed data from 390 patients in the MAKE Biomarker discovery study who were undergoing first-step antidepressant monotherapy with 12 different medications, including escitalopram, paroxetine, sertraline, duloxetine, venlafaxine, desvenlafaxine, milnacipran, mirtazapine, bupropion, vortioxetine, tianeptine, and trazodone, after excluding those with uncommon medications (n=9) or missing biomarker data (n=32). Clinical evaluation by psychiatrists showed favorable mean ratings for correctness (4.3, SD 0.7), consistency (4.2, SD 0.8), specificity (4.2, SD 0.7), helpfulness (4.2, SD 1.0), and human likeness (3.6, SD 1.7) on 5-point scales. These findings demonstrate that reasoning-based LLMs, particularly when enhanced with research-informed prompting, show promise for predicting antidepressant response and could serve as interpretable adjunctive tools in depressive disorder treatment planning, although prospective validation in real-world clinical settings remains..."

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Antidepressants and Risk of Mortality in People with Depressive Disorder and Co-occurring type 2 Diabetes Mellitus: a 20-year Population-based Cohort Study. (PubMed, Psychother Psychosom) - "Depression patients with comorbid type-2 diabetes with exposure to several antidepressant is at decreased mortality risk. Further research is warranted to confirm our findings and clarify the mortality-reducing mechanisms of antidepressant in this vulnerable population."

Journal • Addiction (Opioid and Alcohol) • Cardiovascular • CNS Disorders • Depression • Diabetes • Metabolic Disorders • Mood Disorders • Psychiatry • Type 2 Diabetes Mellitus

Three cases of drug-related death during treatment for stimulant-induced psychosis. (PubMed, Leg Med (Tokyo)) - "Two deaths were directly due to drug overdose (Case 1, chlorpromazine and quetiapine poisoning; Case 2, zotepine and tramadol poisoning). In the third case, the direct cause of death was hanging, but markedly elevated blood concentrations of quetiapine and trazodone suggested that drug intoxication may have contributed to death. Elucidating the pathophysiology of stimulant-induced psychosis and selecting and developing effective treatments are essential, and long-term mental health care and social support to prevent isolation are crucial for preventing unfortunate deaths."

Journal • CNS Disorders • Psychiatry • Schizophrenia

Time Trends in Prescribing of Anxiolytic, Sedative, and Hypnotic Drugs in the United States. (PubMed, Clin Ther) - "The overall shift away from BZ agonist prescribing in the last decade has potential public health drawbacks as well as benefits, the balance of which is not established. The net clinical implications need close analysis using validated and objective biomedical and epidemiologic methodologies."

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

Case Report: A case of drug-induced pancreatitis caused by paroxetine with a literature review. (PubMed, Front Med (Lausanne)) - "She was discharged on trazodone and remains recurrence-free. Clinicians should consider DIP in patients lacking traditional risk factors, especially after self-rechallenge. Early recognition, immediate drug cessation and supportive therapy ensure excellent recovery."

Journal • CNS Disorders • Depression • Dyslipidemia • Immunology • Pain • Pancreatitis • Psychiatry

Update on Medical Treatments for Essential Tremor: An International Parkinson and Movement Disorder Society Evidence-Based Medicine Review. (PubMed, Mov Disord) - "Current evidence from RCTs with at least 1 month of follow-up is insufficient to confidently support the efficacy of available medical treatments for ET. There is a need for longer, higher-quality clinical trials to improve treatment recommendations and guide decision-making for clinicians and patients with ET."

Journal • Review • CNS Disorders • Essential Tremor • Movement Disorders • Parkinson's Disease

Trazodone modulates behavioral alterations in scopolamine-induced cognitive deficit by targeting brain-derived neurotropic factor and cAMP response element-binding protein signaling. (PubMed, Front Cell Neurosci) - "Furthermore, there was a notable upregulation of BDNF and CREB signaling expression, as confirmed by the IHC. Overall, the study findings confirmed that TRAZ could be useful in mitigating the negative effects of scopolamine-induced cognitive impairment and lowering oxidative stress by enhancing memory indicators."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Mood Disorders • Pain • Psychiatry • Aβ42

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

The value of observational studies in MDD research based on the example of trazodone once-a-day. (PubMed, Neurosci Appl) - No abstract available

Journal • Observational data • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

Antidepressants and the risk of hyponatremia: A multi-institutional cohort study using observational medical outcomes partnership-Common Data Model. (PubMed, Br J Clin Pharmacol) - "Close monitoring of serum sodium levels is essential for SSRI users, especially those aged ≥60 years."

Journal • Licensing / partnership • Cardiovascular • CNS Disorders • Depression • Heart Failure • Psychiatry

MDD: Neurobiological and Genomic Predictors of Relapse in Depression (clinicaltrials.gov) - P=N/A | N=204 | Recruiting | Sponsor: Mehmet Kemal Arikan

New trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

CSA-HF: Central Apnea in Heart Failure: Physiological Mechanisms to Inform Treatment (clinicaltrials.gov) - P4 | N=200 | Not yet recruiting | Sponsor: VA Office of Research and Development | Initiation date: Jan 2026 ➔ Oct 2026

Trial initiation date • Cardiovascular • CNS Disorders • Congestive Heart Failure • Heart Failure • Sleep Disorder

CYP2D6 Phenotype as a Predictor of Adverse Drug Reactions in Patients Treated With Trazodone: An Explorative Pharmacogenetic Study. (PubMed, J Clin Psychopharmacol) - "Our findings suggest that mCPP could contribute to trazodone-related ADRs, especially in individuals with reduced CYP2D6 metabolism. Larger clinical studies are needed to confirm that CYP2D6 genotyping could contribute to preventing ADRs in clinical practice."

Adverse drug reaction • Biomarker • Journal • ABCB1 • CYP3A4 • CYP3A5

Do we need to improve pharmacological approaches to treat insomnia in patients with opioid use disorder? (PubMed, Expert Opin Pharmacother) - "A selection of medications, including trazodone and mirtazapine, have been studied as treatments for insomnia among individuals with OUD. Improved pharmacotherapies targeting this pathology are critical not only for enhancing quality of life but also the success of OUD treatment outcomes. Large, rigorous clinical trials are sorely needed to improve sleep medication prescribing guidelines in this population."

Journal • Addiction (Opioid and Alcohol) • CNS Disorders • Insomnia • Sleep Disorder • Substance Abuse

CELESTE: Comparing Digital Therapy, Trazodone, and Daridorexant for Menopause-Related Insomnia Symptoms (clinicaltrials.gov) - P4 | N=1000 | Not yet recruiting | Sponsor: Brigham and Women's Hospital | Trial completion date: Jan 2030 ➔ Feb 2031 | Trial primary completion date: Jan 2030 ➔ Feb 2031

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

Critical evaluation of real-world evidence of repurposable medicines in the Alzheimer's disease drug development pipeline using a target trial emulation. (PubMed, Alzheimers Dement (N Y)) - "This is the first comprehensive set of trial emulations for FDA-approved drugs that are represented in AD trials. Findings may inform future trial designs."

HEOR • Journal • Real-world evidence • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Extreme Rapid Eye Movement Rebound Exceeding Three Hours During Continuous Positive Airway Pressure Titration Despite High-Dose Antidepressant Therapy: A Case Report. (PubMed, Cureus) - "We report a 38-year-old male with severe obstructive sleep apnea (OSA) (apnea-hypopnea index (AHI) = 74.2/hour) receiving fluoxetine 80 mg daily and trazodone 100 mg, who had a 206.5-minute continuous REM sleep episode during CPAP titration, followed by 66.5 minutes of stage N3 sleep. This duration exceeds previously reported continuous REM episodes during titration. This case demonstrates that severe OSA-related sleep fragmentation can overcome potent pharmacological REM suppression when effective treatment is initiated."

Journal • Obstructive Sleep Apnea • Respiratory Diseases • Sleep Disorder

Drug Development. (PubMed, Alzheimers Dement) - "Among the repurposable drugs tested in AD trials, real-world evidence supporting their effectiveness was limited (10%). Notably, bupropion, trazodone, venlafaxine, and zolpidem are potential candidates to reduce AD incidence. Further validation using independent patient data and clinical observations are highly warranted to establish potential clinical benefits of repurposable medicines in AD."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Safety outcomes of trazodone versus antipsychotics for delirium after hospital admission in adults aged 65 years and older: a nationwide cohort study using a target trial emulation framework. (PubMed, Lancet Healthy Longev) - "These results revealed reduced risks of rehospitalisation and all-cause mortality associated with trazodone versus atypical antipsychotic medications. Trazodone is a potentially safer alternative to antipsychotic medications in the management of delirium-related symptoms after hospital discharge."

Journal • Cardiovascular • CNS Disorders • Infectious Disease • Mental Retardation • Nephrology • Pneumonia • Psychiatry • Respiratory Diseases