agomelatine / Generic mfg. - LARVOL DELTA

Serotonin shapes the temporal window for associative fear learning (Neuroscience 2026) - "Importantly, we further show that stress-induced disruption of the associable time window can be rescued by administration of the 5-HT₂C antagonist agomelatine, an atypical antidepressant clinically used to treat anxiety disorders. These findings highlight a key role for serotonin in regulating the temporal precision of fear learning and reveal the DRN-vCA1 serotonergic pathway as a potential therapeutic target for related disorders."

CNS Disorders • Mood Disorders

Circadian rhythm in platelet: an emerging therapeutic target in human diseases. (PubMed, Front Physiol) - "Third, circadian-targeting drugs including tasimelteon, ramelteon, agomelatine, SR9009, VTP-43742, and PF-670462 offer novel therapeutic strategies for rhythm-related disorders. This review highlights the circadian regulation of platelets as an emerging therapeutic target in human diseases."

Journal • Review • Cardiovascular • CNS Disorders • Hematological Disorders • Metabolic Disorders • Thrombosis • NR1D1 • RHOA

Agomelatine as augmentation therapy with second-generation antipsychotics for negative symptoms of schizophrenia: An open-label randomised clinical trial and electroencephalogram-derived model for treatment response prediction. (PubMed, Gen Psychiatr) - P4 | "EEG-based SVM models suggest potential utility for informing future personalised treatment strategies. NCT05646264."

Journal • CNS Disorders • Depression • Psychiatry • Schizophrenia

Role of the Amygdala in the Complex Relationship Between Sleep and Anxiety. (PubMed, Int J Mol Sci) - "Trazodone, a serotonin antagonist and reuptake inhibitor (SARI), improves sleep by blocking serotonin receptors and is effective in treating post-traumatic stress disorder (PTSD) related sleep disturbances...At the same time, agomelatine, an antidepressant with anxiolytic properties, improves sleep quality without disrupting REM sleep and treats insomnia associated with various conditions, including alcohol dependence. The aim of this review is to summarize amygdala functions, with a focus on their role in regulating sleep and affective responses. Moreover, it discusses possible therapeutic targets in the amygdala for anxiety and sleep disorders."

Journal • Review • Addiction (Opioid and Alcohol) • CNS Disorders • Insomnia • Mood Disorders • Post-traumatic Stress Disorder • Psychiatry • Sleep Disorder

Agomelatine decreased cocaine-induced locomotor activity in rats; a dose-time response study. (PubMed, Front Pharmacol) - "Additionally, a 30 mg/kg dose of agomelatine administered for 10 days decreased locomotor activity induced by binge-pattern cocaine administration. Collectively, these findings suggest that a dosage of 10 mg/kg of agomelatine administered for 10 consecutive days effectively attenuates the long-term behavioral effects of cocaine."

Journal • Preclinical • CNS Disorders • Depression • Hepatology • Major Depressive Disorder • Mood Disorders • Psychiatry • Substance Abuse

Back to gut feelings. Latent class analysis of daily perceived health variations identifies later responses to antidepressant treatment. (PubMed, Psychother Psychosom) - "In this multicentre naturalistic study, 1536 outpatients with MDD initiating agomelatine monotherapy were recruited across 388 community psychiatry centers...Patients with rapid early improvement had the highest remission rates, whereas those with severe baseline symptoms and limited early improvement had the poorest outcomes. These findings support the clinical utility of early wellbeing trajectories for personalized monitoring during antidepressant treatment."

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

RETRACTED: Wigner et al. The Impact of Chronic Mild Stress and Agomelatine Treatment on the Expression Level and Methylation Status of Genes Involved in Tryptophan Catabolic Pathway in PBMCs and Brain Structures. Genes 2020, 11, 1093. (PubMed, Genes (Basel)) - "The journal retracts the article titled, "The Impact of Chronic Mild Stress and Agomelatine Treatment on the Expression Level and Methylation Status of Genes Involved in Tryptophan Catabolic Pathway in PBMCs and Brain Structures" [...]."

Biomarker • Journal

Melatoninergic Modulation of Benzene-Induced Pre-Leukemic Alterations in Rats: Effects of Melatonin, Agomelatine, and Luzindole : Short title: Melatoninergic Modulation in Benzene-Induced Pre-Leukemi. (PubMed, Galen Med J) - "Melatonin and agomelatine attenuated several hematological, genotoxic, and oxidative alterations in benzene-exposed rats. Luzindole partially modified these effects, suggesting possible melatonin receptor involvement alongside non-receptor antioxidant and anti-inflammatory actions."

Journal • Preclinical • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Part A Phase I, Single Ascending Dose Trial of Agomelatine in Healthy Participants (ANZCTR) - P1 | N=15 | Completed | Sponsor: Seaport Therapeutics Australia Pty LTD | Recruiting ➔ Completed

Trial completion • Mood Disorders • Psychiatry

Comparative Efficacy and Acceptability of 21 Antidepressant Drugs for the Acute Treatment of Adults With Major Depressive Disorder: A Systematic Review and Network Meta-Analysis. (PubMed, Focus (Am Psychiatr Publ)) - "In head-to-head studies, agomelatine, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine, and vortioxetine were more effective than other antidepressants (range of ORs 1·19-1·96), whereas fluoxetine, fluvoxamine, reboxetine, and trazodone were the least efficacious drugs (0·51-0·84). For acceptability, agomelatine, citalopram, escitalopram, fluoxetine, sertraline, and vortioxetine were more tolerable than other antidepressants (range of ORs 0·43-0·77), whereas amitriptyline, clomipramine, duloxetine, fluvoxamine, reboxetine, trazodone, and venlafaxine had the highest dropout rates (1·30-2·32)...These results should serve evidence-based practice and inform patients, physicians, guideline developers, and policy makers on the relative merits of the different antidepressants. National Institute for Health Research Oxford Health Biomedical Research Centre and the Japan Society for the Promotion of Science.Appeared..."

Journal • Retrospective data • Bipolar Disorder • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry

Cognitive Impairment Associated with Chemotherapy: Neuroimmunological Interactions, Gut-Brain Axis, and Therapeutic Approaches. (PubMed, Brain Sci) - "Pharmacological candidates-including lithium, fluoxetine, methylphenidate, modafinil, metformin, agomelatine, and melatonin-as well as nutritional and lifestyle interventions such as physical exercise, omega-3 fatty acids, curcumin, probiotics, and traditional Chinese medicine formulations-have been investigated, predominantly in animal models. However, optimal strategies for symptom improvement remain unclear, as various approaches have yielded mixed outcomes. This review provides a comprehensive overview of chemobrain, focusing on its molecular mechanisms, interactions with the gut-brain axis, and potential therapeutic targets to improve the quality of life for cancer survivors."

Journal • Review • Alzheimer's Disease • Cognitive Disorders • Metabolic Disorders • Oncology • GFAP

Investigation of the Effects of Agomelatine in Rats with Experimental Cerebral Ischemia/Reperfusion Model. (PubMed, Biomedicines) - " Agomelatine attenuated neurological deficits and infarct formation following CI/R injury. These neuroprotective effects may be associated with suppression of apoptosis and enhancement of autophagy-related pathways."

IO biomarker • Journal • Preclinical • Cardiovascular • Ischemic stroke • Reperfusion Injury • ATG7 • BCL2 • BECN1

Hyponatremia risk with antidepressant use: A retrospective study. (PubMed, J Chin Med Assoc) - "These findings underscore the complexity of hyponatremia etiologies and highlight the need for individualized treatment strategies that account for comorbidities and potential drug interactions."

Journal • Retrospective data • Cardiovascular • Diabetes • Heart Failure • Metabolic Disorders • Oncology

Seizures Temporally Associated With SSRI Treatment: A Two-Case Report Exploring Agomelatine as a Treatment Alternative. (PubMed, Case Rep Psychiatry) - "The second case is a woman with generalized anxiety disorder (GAD) who developed two generalized tonic-clonic seizures temporally related to paroxetine use. Both patients were subsequently switched to the atypical antidepressant agomelatine, which was followed by a complete cessation of seizures and marked improvement in mood and anxiety symptoms. These observations underscore the need to consider seizures as a potential adverse event of SSRIs and suggest that agomelatine could be considered an alternative pharmacological option for patients at risk of antidepressant-associated seizures."

Journal • CNS Disorders • Depression • Epilepsy • General Anxiety Disorder • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Sexual Disorders • Sleep Disorder

Retraction Note: Nasal In-Situ Gels of Brij®-Enriched Novasomes as Optimistic Nanovesicular Carriers for Enhancing Anti-Depressant Action of Agomelatine. (PubMed, AAPS PharmSciTech) - No abstract available

Journal

Discovering the Differences of the Individual Batches of API and its Polymorphs Using Hansen Solubility Parameters. (PubMed, Pharm Res) - "IGC-derived HSP analysis provides complementary, surface-sensitive information that can support excipient selection during early formulation development and help manage risks related to polymorphic variability and supplier-to-supplier differences. Further work should link HSP profiles to formulation performance metrics such as processability, compatibility and stability."

Journal

Agomelatine versus gefitinib against HepG2 cells: Modulating PI3K/AKT and MAPK/RAF1/c-FOS pathways. (PubMed, Mol Biol Rep) - "Our results demonstrated that both AGO and GEF impeded HCC progression by enhancing apoptosis and caspase expression while modulating the PI3K/AKT and MAPK/RAF/c-FOS signaling pathways, suggesting that AGO and GEF may serve as effective therapeutic options for HCC, with gefitinib exhibiting greater potential as an anticancer agent."

Journal • Hepatocellular Cancer • Oncology • Solid Tumor • AKT1 • CASP8 • CASP9 • FOS • MAPK1 • RAF1

Agomelatine for Sjögren's syndrome: a study on its therapeutic effects and mechanisms. (PubMed, Inflammopharmacology) - "AGO significantly improved behavioral performance, reduced the proportion of Th1 cells in the spleen, and alleviated inflammatory infiltration in the salivary glands of NOD mice. These findings suggest that the drug may exert therapeutic effects by modulating immune responses and neurobehavioral functions, positioning it as a promising candidate for the treatment of SS."

Journal • CNS Disorders • Dental Disorders • Depression • Dry Eye Disease • Fatigue • Immunology • Inflammation • Obesity • Ophthalmology • Psychiatry • Sjogren's Syndrome • Xerostomia

Neuropathophysiological changes associated with mirtazapine treatment response in major depressive disorder: insights into bottom-up dopaminergic pathways and prefrontal control networks. (PubMed, Eur Arch Psychiatry Clin Neurosci) - "Sixty-seven individuals with MDD underwent functional magnetic resonance imaging during a conditioned reward task and then received monotherapy with mirtazapine or one of two comparator antidepressants (agomelatine or a selective serotonin reuptake inhibitor). Importantly, many of these response-related activations were specific to the mirtazapine group. These findings suggest that altered engagement of mesolimbic dopaminergic pathways and prefrontal regulatory networks during reward processing may characterize an MDD subtype responsive to mirtazapine, and that such patterns may serve as biomarkers for identifying patients likely to benefit from this treatment."

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

Antidepressant-Induced Sexual Dysfunction in Adults: A Targeted Scoping Review and Clinical Update. (PubMed, J Clin Psychopharmacol) - "AISD is a multifactorial adverse effect of antidepressant therapy that may persist in some individuals and can adversely affect quality of life and treatment adherence. Systematic assessment and individualized intervention may help mitigate impact, though optimal strategies remain incompletely defined. Increased recognition of PSSD highlights the need for further methodologically rigorous research into its pathophysiology, prevalence, and treatment."

Journal • Sexual Disorders

Comparative efficacy of agomelatine and escitalopram in people with epilepsy and comorbid major depressive disorder: A double-blind randomized controlled trial. (PubMed, Epilepsy Behav Rep) - "Escitalopram showed a more consistent pattern of benefit on mood and QoL, whereas cognitive effects were limited after correction for multiple testing. Larger studies are needed to confirm these findings."

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

Investigating the effects of antidepressants on measures of insulin resistance in major depressive disorder: A systematic review. (PubMed, J Affect Disord) - "The effect of antidepressants on mechanisms mediating insulin sensitivity is mixed, with a relatively limited body of evidence currently available. While select SSRIs and tricyclic antidepressants may adversely affect glucose-insulin homeostasis, conclusions remain preliminary. The development of novel antidepressants may provide an opportunity to optimize psychiatric and metabolic outcomes. Identifying mechanisms contributing to insulin resistance could inform future discovery and development of antidepressants."

Journal • Review • CNS Disorders • Depression • Diabetes • Major Depressive Disorder • Metabolic Disorders • Mood Disorders • Psychiatry

Neuroanatomical characteristics associated with mirtazapine response in major depressive disorder (OHBM 2026) - "Patients were assigned to receive monotherapy with mirtazapine (n=23) or one of the comparator antidepressants: agomelatine (n=20) or a selective serotonin reuptake inhibitor (n=25). The authors acknowledge support by the state of Baden-Württemberg through bwHPC and the German Research Foundation (DFG) through grant INST 35/1597-1 FUGG. Data storage service SDS@hd was supported by the Ministry of Science, Research and the Arts Baden-Württemberg (MWK) and the German Research Foundation (DFG) through grant INST 35/1314-1 FUGG and INST 35/1503-1 FUGG."

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

Breaking the Cycle of Insomnia and Depression: Agomelatine in Adolescent Bipolar Disorder. (PubMed, Psychopharmacol Bull) - "These cases suggest that adjunctive agomelatine may offer a dual benefit of sleep regulation and mood stabilization in adolescent BD, representing a promising alternative in patients who have failed or cannot tolerate conventional antidepressants. Controlled clinical trials are warranted to confirm these preliminary findings."

Clinical • Journal • Bipolar Disorder • CNS Disorders • Depression • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder

Mechanistic Study of the Antidepressant Agomelatine in Modulating STING Activity During the Pathogenesis of Systemic Lupus Erythematosus (EULAR 2026) - "Peritoneal macrophages (PEMs) were were stimulated with various stimuli, including lipopolysaccharide (LPS), interferon-stimulatory DNA (ISD), herpes simplex virus (HSV), cyclic GMP-AMP (cGAMP), ABT-737 + QVD-OPh, at different time points (0 h, 3 h, 6 h)...RT-qPCR results showed that the EGFR inhibitor Dacomitinib attenuated the suppressive effect of AGO on IFN-related gene expression in ISD/cGAMP-stimulated macrophages...Behavioral tests, including the tail suspension test (TST), forced swim test (FST), and open field test (OFT), demonstrated that AGO significantly ameliorated depression-like behaviors in lupus model mice. Conclusions This study elucidates the molecular mechanism by which the antidepressant AGO modulates STING activity and the subsequent production of IFN-I, thereby laying a theoretical foundation of novel therapeutics for SLE."

Cardiovascular • CNS Disorders • Depression • Herpes Simplex • Immunology • Inflammatory Arthritis • Lupus • Mood Disorders • Sleep Disorder • Systemic Lupus Erythematosus • CCL2 • CXCL1 • CXCL10 • CXCL12 • CXCL5 • CXCL9 • IFNB1 • IRF7 • MX1 • STING