agomelatine / Generic mfg. - LARVOL DELTA

Impact of a stepwise pharmacologic intervention on moderate-to-severe chronic insomnia: a German observational study (WSS 2025) - "Materials and Patients with moderate-to-severe insomnia where cognitive behavioral therapy was ineffective were asked for participation in the study and received a stepwise pharmacologic intervention, starting with L-tryptophan, melatonin, or agomelatine (S1 medication)... A stepwise therapeutic approach should be used for patients with moderate-to-severe insomnia. Even if only 14% remained on S1 substances after 9 months, the quality of sleep and the severity of insomnia improved significantly – independently of the initial severity of the disorder."

Clinical • Observational data • CNS Disorders • Insomnia • Sleep Disorder

Severe, refractory restless legs syndrome responding to hyperbaric oxygen therapy: a case report (WSS 2025) - "At the time of hyperbaric oxygen therapy (HBOT) initiation, she was taking buprenorphine patch 5 mcg/h weekly, amitriptyline 25 mg nocte, agomelatine 25 mg daily, gabapentin 600 mg daily, and zopiclone 7.5 mg nocte. This case highlights the potential for HBOT to serve as a novel adjunctive therapy for patients with refractory RLS, particularly when conventional treatment options have been exhausted. If further validated, HBOT may offer a promising avenue for improving quality of life in this challenging patient population."

Case report • Clinical • CNS Disorders • Insomnia • Movement Disorders • Respiratory Diseases • Restless Legs Syndrome • Sleep Apnea • Sleep Disorder

Managing Insomnia in an Adult Female with ADHD and Sedative Abuse: A Case Report on the Combined Use of Lemborexant, Agomelatine, and Methylphenidate (WSS 2025) - "She had a longstanding diagnosis of adult ADHD and a history of alprazolam abuse. Managing insomnia in adults with ADHD and prior sedative abuse is clinically challenging. However, this case demonstrates that a thoughtfully designed regimen—combining lemborexant, agomelatine, and methylphenidate—can lead to meaningful improvement in both sleep and daytime functioning. The key lies in targeting complementary neurobiological mechanisms: orexin inhibition for arousal, melatonergic support for circadian rhythm, and dopaminergic enhancement for executive dysfunction."

Case report • Clinical • ADHD (Impulsive Aggression) • Anesthesia • Attention Deficit Hyperactivity Disorder • CNS Disorders • Insomnia • Psychiatry • Sleep Disorder

Agomelatine Alleviates Chronic Social Defeat Stress-Induced Synaptic Impairments via STAT3 Signaling (WFSBP 2025) - "These findings indicate that agomelatine improves synaptic plasticity impairments in depression via the STAT3 phosphorylation. STAT3-regulated downstream molecules may serve as potential therapeutic targets for the rapid action of antidepressants."

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

Agomelatine Ameliorates Cognitive and Behavioral Deficits in Aβ-Induced Alzheimer's Disease-like Rat Model. (PubMed, Medicina (Kaunas)) - "Nestin levels differed significantly between control and AD animals; MT1 expression varied between control and AD cohorts; and MT2 transcript levels were significantly lower in AD, ADAgo, and Ago groups compared to C (all p < 0.05). Ago exhibits antidepressant-like activity in this experimental AD model and may enhance cognitive function via mechanisms beyond synaptic plasticity and neurogenesis."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Metabolic Dysfunction-Associated Steatohepatitis • BDNF • DCX • NES

Comparative efficacy and acceptability of anxiolytic drugs for the treatment of anxiety disorders: a systematic review and network meta-analysis. (PubMed, Eur Arch Psychiatry Clin Neurosci) - "This network meta-analysis provides a unique comparison of the efficacy and acceptability of anxiolytics. It represents one of the most comprehensive evidence bases available to guide the first choice of treatment for anxiety disorders in adults."

Journal • Retrospective data • CNS Disorders • General Anxiety Disorder • Mood Disorders • Psychiatry

Agomelatine and Empagliflozin Synergistically Protect Against Diabetic Cardiomyopathy via Nrf2/HO-1 Signaling. (PubMed, Eur J Pharmacol) - "It also effectively suppressed myocardial inflammation, fibrosis, and apoptosis, as evidenced by reduced NF-κB, TGF-β, and caspase-3 expression. These findings demonstrate the synergistic cardioprotective effects of combining AGM and EMPA in DCM, suggesting that this low-dose combination therapy may offer a promising new therapeutic strategy for managing this challenging condition."

Journal • Cardiomyopathy • Cardiovascular • Diabetes • Fibrosis • Immunology • Inflammation • Metabolic Disorders • CASP3 • TGFB1

Combined effects of agomelatine and 2600 MHz radiofrequency field on inflammation induced by chronic lipopolysaccharide administration. (PubMed, Electromagn Biol Med) - "In the hypothalamus, chronic LPS exposure was associated with a downregulation of MAP kinase signaling pathways (ERK, JNK), indicative of endotoxin tolerance, and with reduced NF-κB level. This study provides novel evidence that 2600 MHz RF, when combined with AGM, may exert a powerful anti-inflammatory effect, highlighting a potential therapeutic interaction that warrants further investigation."

Journal • Inflammation • IL1B • IL6 • TNFA

The role of agomelatine in appetite regulation and body weight in rats. (PubMed, Exp Physiol) - "Hypothalamic orexigenic neuropeptides neuropeptide Y (NPY) and agouti-related peptide (AgRP) were suppressed (NPY, Ago40: 0.61 ± 0.02 vs. Control: 1.36 ± 0.1321; AgRP, Ago40: 0.52 ± 0.03 vs. Control: 1.49 ± 0.27, P < 0.05), while anorexigenic cocaine- and amphetamine-regulated transcript (CART) and proopiomelanocortin (POMC) were elevated (CART: Ago40: 1.19 ± 0.08 vs. Control: 0.92 ± 0.06; POMC: Ago40: 1.49 ± 0.17 vs. Control: 0.67 ± 0.10, P < 0.05). These findings suggest agomelatine promotes weight loss by modulating appetite-related hormones and hypothalamic neuropeptides, highlighting its potential as a therapeutic for obesity and metabolic disorders."

Journal • Preclinical • Genetic Disorders • Metabolic Disorders • Obesity • POMC-null Obesity • LEP

Electrochemical detection of agomelatine using a high-performance FeZn LDH/graphene/polyaniline nanocomposite sensor for clinical and pharmaceutical analysis. (PubMed, Mikrochim Acta) - "The sensor maintained performance against 100-fold excesses of common interferents (e.g., glucose, ascorbic acid, Na+, Ca2+). By overcoming key limitations in plasma compatibility and sensitivity, this FeZn LDH/graphene/polyaniline sensor offers a robust, sustainable platform for real-time AG monitoring, directly applicable in clinical diagnostics and pharmaceutical quality control."

Journal

Ameliorative effects of agomelatine against doxorubicin-induced hepatotoxicity. (PubMed, BMC Pharmacol Toxicol) - "Doxorubicin induces oxidative stress, apoptosis, and hepatotoxicity. Agomelatine may be favored as a primary antidepressant to mitigate hepatic damage induced by doxorubicin."

Journal • Hematological Disorders • Oncology • CASP3 • TNFA

Efficacy and Safety of Electroacupuncture Combined with Agomelatine Tablets Therapy in Treating Insomnia After Stroke. (PubMed, J Mol Neurosci) - "These findings demonstrate that EA + AT combination therapy outperforms monotherapies in treating post-stroke insomnia. In conclusion, this study establishes EA + AT as an effective intervention for improving both sleep quality and cognitive function in stroke-related insomnia patients, offering a promising therapeutic strategy for this clinical condition."

Clinical • Journal • Cardiovascular • CNS Disorders • Depression • Insomnia • Psychiatry • Sleep Disorder

Safety Evaluation of Agomelatine Use in Children and Adolescents (ChiCTR) - P=N/A | N=100 | Not yet recruiting | Sponsor: West China Hospital of Shichuan University; West China Hospital of Shichuan University

New trial • CNS Disorders • Depression • Mood Disorders • Psychiatry

Assessing the role of drug interventions in the polycystic ovary syndrome model. (PubMed, Naunyn Schmiedebergs Arch Pharmacol) - "The research was devised to assess the prophylactic effects of agomelatine, a melatonin receptor antagonist, against letrozole-induced polycystic ovarian syndrome (PCOS) in 56 female rats divided randomly into seven groups of eight rats each. Agomelatine significantly attenuated these adverse effects, demonstrating its potential as a therapeutic agent for PCOS. However, further research is necessary to elucidate its mechanisms of action and assess its clinical relevance in human PCOS treatment."

Journal • Cognitive Disorders • Polycystic Ovary Syndrome

Agomelatine alleviates palmitic acid-induced mouse oocyte meiosis defects by restoring mitochondrial function. (PubMed, Int J Obes (Lond)) - "This study establishes that Ago ameliorates metabolic stress-induced oocyte deterioration through mitochondrial functional restoration, providing mechanistic insights into obesity-associated infertility. Importantly, our study identifies a potentially favorable drug for combating obesity-induced female infertility."

Journal • Preclinical • Genetic Disorders • Gynecology • Infertility • Obesity • Sexual Disorders

Fluoxetine and agomelatine mitigate anhedonic and hepatic changes in chronic restraint stress rat model. (PubMed, Sci Rep) - "Additionally, both drugs significantly reduced the upregulation of caspase-3 (***P ≤ 0.001) and proliferating cell nuclear antigen (PCNA, ***P ≤ 0.001) in CRS rats. This study revealed for the first time the potential therapeutic role of fluoxetine and agomelatine on the liver during the CRS depression model by controlling oxidative stress and hepatic regeneration."

Journal • Preclinical • CNS Disorders • Depression • Psychiatry • CASP3 • PCNA

Dissecting the pro-neurogenic effects of monoaminergic medications used to treat depression: a systematic review and meta-analysis. (PubMed, J Psychopharmacol) - "The available number of studies was also insufficient to yield definitive evidence for compounds acting as selective serotonin reuptake inhibitors (citalopram, escitalopram, fluvoxamine), serotonin-norepinephrine reuptake inhibitors (desvenlafaxine, duloxetine, venlafaxine), multimodal monoaminergic modulators (imipramine, desipramine), melatonergic compound (agomelatine), or norepinephrine-serotonin disinhibitory (mirtazapine). Subsequent updates of these reviews appear necessary to establish robust evidence regarding these compounds. Evidence was firm in favor of a robust pro-neurogenic effect of selective serotonin reuptake inhibitor fluoxetine, in both species, making updates of this review probably redundant."

Journal • Retrospective data • Review • CNS Disorders • Depression • Mood Disorders • Psychiatry

Agonism of MT1 and MT2 Receptor Mitigates Oxidative Insult, Neuroinflammation, and Cerebral Injury in Cadmium Chloride Treated Animals. (PubMed, Neurochem Res) - "It also restored the antioxidant status, neurotransmitter levels, cerebral health and suppressed neuroinflammation. The neuroprotective effects of agomelatine on CdCl2 provoked toxic effects in experimental animals' brains, suggesting its therapeutic potential as an antioxidant and neuroprotectant agent."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Inflammation • Oncology • Pain • Psychiatry • BDNF • IL6 • MPO • TNFA

Switching Medication and Augmentation Strategies for SSRI-Resistant Adolescent Depression（SMART-I) (clinicaltrials.gov) - P4 | N=400 | Not yet recruiting | Sponsor: Xinyu Zhou

New P4 trial • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Psychiatry

The Neuroprotective Impact of Agomelatine in Preserving Brain Tissue Molecular Structure Against Alzheimer's Disease Etiology. (PubMed, Neurochem Res) - "FTIR spectroscopy revealed agomelatine's protective effect on brain molecular structure, mainly through preserving lipid order in the CH stretching region and preventing protein oxidation in the C = O spectral range, both of which are typically altered by AD pathology. These results emphasize the efficacy of agomelatine and support its consideration in mitigating symptoms associated with AD etiology."

Journal • Alzheimer's Disease • CNS Disorders • IL6

Part A Phase I, Single Ascending Dose Trial of Agomelatine in Healthy Participants (ANZCTR) - P1 | N=10 | Not yet recruiting | Sponsor: Seaport Therapeutics Australia Pty LTD

New P1 trial • Mood Disorders • Psychiatry

Agomelatine, a multi-target drug, does not alter basal locomotor activity in rats. (PubMed, J Psychiatr Res) - "These results suggest that agomelatine, at different doses, does not cause sustained sedation but may transiently suppress locomotion at higher doses."

Journal • Preclinical • Anesthesia • CNS Disorders • Depression • Mood Disorders • Psychiatry

Insulin Resistance: The Role in Comorbid Type 2 Diabetes Mellitus and Depression. (PubMed, Neurosci Biobehav Rev) - "Tricyclic antidepressants, particularly amitriptyline and nortriptyline, worsen metabolic profiles by exacerbating IR, promoting weight gain, and inducing hyperglycemia, thereby increasing diabetes risk with prolonged use...Mirtazapine presents a paradoxical profile-while its appetite-stimulating effects often lead to weight gain (a known IR risk factor for IR), some evidence suggests potential β-cell function preservation, necessitating cautious use of mirtazapine in individuals with metabolic syndrome. Among selective serotonin reuptake inhibitors, fluoxetine and escitalopram demonstrate favorable metabolic effects, including improved insulin sensitivity and glycemic control, though hypoglycemia risk (particularly with concomitant sulfonylureas) warrants monitoring. Bupropion, a norepinephrine-dopamine reuptake inhibitor, uniquely promotes weight loss and enhances glycemic control, making it a first-line option for depression comorbid with obesity or T2DM. Agomelatine,..."

Journal • Review • CNS Disorders • Depression • Diabetes • Genetic Disorders • Hypoglycemia • Inflammation • Metabolic Disorders • Mood Disorders • Obesity • Psychiatry • Type 2 Diabetes Mellitus

Did Serendipity Contribute to the Discovery of New Antidepressant Drugs? Historical Analysis Using Operational Criteria. (PubMed, Alpha Psychiatry) - "Selective serotonin reuptake inhibitors (fluoxetine, fluvoxamine, citalopram, paroxetine, sertraline, and escitalopram), selective dopamine and noradrenaline reuptake inhibitors (bupropion), noradrenaline and serotonin reuptake inhibitors (venlafaxine, milnacipram, duloxetine, and desvenlafaxine), selective noradrenaline reuptake inhibitors (reboxetine), noradrenergic and specific serotonergic antidepressants (mirtazapine), melatonergic agonists (agomelatine), and serotonin modulators and stimulators (vortioxetine, vilazodone, tianeptine) correspond to the type IV pattern. Ketamine, a glutamatergic modulator, corresponds to the type III pattern, characterized by a non-serendipitous origin (initial development as an anesthetic agent) leading to a serendipitous observation (the discovery of antidepressant efficacy in individuals illicitly using). The majority of new antidepressants adhere to a type IV pattern, characterized by a rational and targeted design process where..."

Journal • Anesthesia

Comparative efficacy of antidepressant medication for adolescent depression: a network meta-analysis and systematic review. (PubMed, BMC Psychiatry) - "For symptom severity scales, agomelatine (CDRS-R: SUCRA 86.4%) and paroxetine (MADRS: SUCRA 99.9%) demonstrated the greatest efficacy. For functional improvement, escitalopram ranked highest on CGAS (SUCRA 96.1%). Sertraline showed superiority in clinician-rated severity (CGI-S: SUCRA 100%) and improvement (CGI-I: SUCRA 80.2%). Clinical decisions should prioritize escitalopram for functional recovery and sertraline for severe cases requiring rapid symptom reduction."

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