agomelatine / Generic mfg. - LARVOL DELTA

Investigating the Role of GABAergic Interneurons in the Antidepressant-like Mechanism of Agomelatine. (PubMed, Neurochem Int) - "The antidepressant effects of AGO involve the modulation of GABAergic neural circuits as a critical but non-exclusive target, alongside the restoration of GABAergic-glutamatergic balance, synaptic function, and clock gene expressions. These findings highlight AGO's potential in normalizing disrupted neuronal function in depression and offer insights into novel multi-target therapeutic strategies."

Journal • CNS Disorders • Depression • Mental Retardation • Psychiatry • CLOCK • SLC2A1

A Novel Zeolite-Carbon Nanotube Composite Electrode for the Electrochemical Analysis of Agomelatine in Real Samples. (PubMed, Nanomaterials (Basel)) - "Differential pulse voltammetry (DPV) was utilized for the quantitative determination of AGO, with optimization performed on instrumental parameters, supporting electrolyte pH, and preconcentration time (tacc). Using the Britton-Robinson buffer (BRB) solution at pH 3.0, the Cu-ZY/MWCNTs-GCE exhibited a linear response to AGO concentrations ranging from 8.2 × 10-9-9.6 × 10-7 mol L-1 (0.002-0.23 mg L-1), achieving a detection limit (LOD) of 4.3 × 10-9 mol L-1 (1.04 µg L-1) with a preconcentration time of 60 s. The successful determination of AGO in pharmaceutical formulations, wastewater, and biological fluids, with recoveries ranging from 98.0 to 113.0%, demonstrates the effectiveness and practical applicability of the Cu-ZY/MWCNT-GCE-based voltammetric method for agomelatine analysis in complex matrices."

Journal

Agomelatine alleviates hypoxia-induced pulmonary arterial hypertension by activating mitophagy via the SIRT1/FoxO1/ULK1 signaling pathway. (PubMed, Biochem Pharmacol) - "The present investigation was designed to evaluate the ameliorative potential of AGM on pulmonary vascular remodeling in a SU5416/hypoxia (SuHx)-induced PAH rat model, and to elucidate the concomitant mechanistic pathways. In contrast, inhibition of SIRT1 resulted in increased FoxO1 acetylation, which subsequently downregulated ULK1 expression and impaired mitophagy. Collectively, these findings establish that AGM exerts therapeutic effects in PAH by enhancing ULK1-dependent mitophagy through modulation of the SIRT1/FoxO1 signaling axis, underscoring its potential as a novel therapeutic candidate for PAH."

Journal • Cardiovascular • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Effects and Mechanisms of Melatonin Receptor Agonist and Antagonist on Disease Progression in a 6-OHDA-Induced Parkinson's Disease Rat Model. (PubMed, J Integr Neurosci) - "Both AG and LU demonstrated neuroprotective potential in 6-OHDA-induced PD rats. AG may exert its effects by enhancing endogenous MLT signaling, while LU may protect neurons by modulating excessive MLT activity. These findings highlight the complex regulatory role of the MLT pathway in PD progression and suggest stage-dependent therapeutic benefits of MLT receptor modulators."

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

Agomelatine normalizes region-specific, diurnal mGluR5 dysregulation in a chronic mild stress rat model of depression. (PubMed, Prog Neuropsychopharmacol Biol Psychiatry) - "These findings reveal significant region-specific and diurnal alterations in mGluR5, emphasizing the role of time-of-day dependent timing in regulating mGluR5 and its association with depressive-like behaviors. Furthermore, the selective normalization of mGluR5 by agomelatine in responders reinforces its potential as a targeted therapeutic approach for MDD."

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

Serotonin receptor 4 in the ventral CA3 regulates agomelatine-induced anxiolytic-like behaviors. (PubMed, Acta Pharmacol Sin) - "Together, these results suggest that agomelatine's anxiolytic effects are closely associated with the suppression of 5-HTR4 expression in the vCA3, along with modulation of neuronal activity and GPCR signaling. This study not only uncovers the molecular mechanisms underlying agomelatine's anxiolytic mechanism but also identifies 5-HTR4 as a potential target for anxiety disorders."

Journal • CNS Disorders • Insomnia • Mood Disorders • Psychiatry • Sleep Disorder • CA3 • FOS

Comparative gastrointestinal effects of antidepressants for the acute treatment of adults with major depressive disorder: a network and dose‒response meta-analysis. (PubMed, Transl Psychiatry) - "Commonly used antidepressants have different gastrointestinal effects. Duloxetine, levomilnacipran, and vilazodone carry a higher risk of inducing nausea and vomiting, whereas trazodone, amitriptyline, agomelatine, and mirtazapine tend to be better tolerated. Amitriptyline, clomipramine, and reboxetine are more prone to induce constipation. Diarrhoea is more commonly associated with vilazodone, fluvoxamine, and sertraline. Amitriptyline, reboxetine, and duloxetine are more likely to cause anorexia. Amitriptyline, reboxetine, and trazodone are related to causing dry mouth. Compared with the placebo, amitriptyline, fluoxetine, and paroxetine were associated with a greater incidence of dyspepsia."

Journal • Retrospective data • Review • Anorexia • CNS Disorders • Constipation • Depression • Dyspepsia • Gastroenterology • Gastrointestinal Disorder • Major Depressive Disorder • Mood Disorders • Psychiatry • Xerostomia

Agomelatine Targets Aquaporin-4 Polarization to Rescue Glymphatic Dysfunction in Parkinson's Disease. (PubMed, Neurosci Bull) - "Our findings establish AGM as the first melatoninergic agent targeting the glymphatic-AQP4 axis in PD, shifting therapeutic strategies from symptomatic relief to disease modification. This provides clinical rationale for repurposing circadian regulators to decelerate PD progression through enhanced protein clearance."

Journal • CNS Disorders • Mood Disorders • Movement Disorders • Parkinson's Disease • Psychiatry • ARNTL • BMAL1

Excessive Yawning Induced by Duloxetine in a Patient With Depression With Successful Agomelatine Substitution: A Case Report. (PubMed, Am J Ther) - No abstract available

Journal • CNS Disorders • Depression • Mood Disorders • Psychiatry

Part A Phase I, Single Ascending Dose Trial of Agomelatine in Healthy Participants (ANZCTR) - P1 | N=15 | Recruiting | Sponsor: Seaport Therapeutics Australia Pty LTD | Not yet recruiting ➔ Recruiting | N=10 ➔ 15

Enrollment change • Enrollment open • Trial initiation date • Mood Disorders • Psychiatry

Effects of Agomelatine on Sleep Across Populations: A Systematic Review and Meta-Analysis. (PubMed, J Sleep Res) - "Agomelatine was found to cause marginally more adverse effects than placebo (RR = 1.05, 95% CI: 1.00; 1.11). Overall, agomelatine appears to slightly improve sleep quality and is well-tolerated and safe, although the limited data for many outcomes warrant cautious interpretation."

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

Evaluating the Quality of Evidence for Pharmacological Treatment of Depressive Disorders (AACAP 2025) - "SSRIs (GRADES 1A-2C) and SNRIs (1B) are effective in the treatment of pediatric MDD. Tricyclic antidepressants (2B) and monoamine oxidase inhibitors (2C) have failed to consistently demonstrate efficacy, and they have unfavorable risk-to-benefit profiles. Esketamine, agomelatine, bupropion, transcranial magnetic stimulation, and other emerging classes of treatment may be safe and effective but merit further testing.ADP, DDD, NM"

CNS Disorders • Depression • Mood Disorders • Pediatrics • Psychiatry

Oleic acid Enriched Leciplexes as Novel Mucoadhesive Cationic Nanocarriers of Agomelatine for Glaucoma Treatment. (PubMed, AAPS PharmSciTech) - "AGO pharmacodynamic and histopathological studies were conducted in rabbits. Compared to AGO dispersion, elevated maximum IOP reduction (74.2%), prolonged mean residence time (12.88 h), enhanced bioavailability (3 folds) and normal histopathological micrographs proved the potential of L20 leciplex in improving and sustaining the ocular bioavailability of AGO and maintaining its safety."

Journal • CNS Disorders • Depression • Glaucoma • Ophthalmology • Psychiatry

The effects of antidepressants on cardiometabolic and other physiological parameters: a systematic review and network meta-analysis. (PubMed, Lancet) - "We found strong evidence that antidepressants differ markedly in their physiological effects, particularly for cardiometabolic parameters. Treatment guidelines should be updated to reflect differences in physiological risk, but choice of antidepressant should be made on an individual basis, considering clinical presentation and preferences of patients, carers, and clinicians."

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

Side effect profile and comparative tolerability of newer generation antidepressants in the acute treatment of major depressive disorder in children and adolescents: protocol for a systematic review and network meta-analysis. (PubMed, BMJ Open) - "The following antidepressants will be considered: agomelatine, alaproclate, bupropion, citalopram, desvenlafaxine, duloxetine, edivoxetine, escitalopram, fluoxetine, fluvoxamine, levomilnacipran, milnacipran, mirtazapine, paroxetine, reboxetine, sertraline, venlafaxine, vilazodone and vortioxetine. The findings will be published in a peer-reviewed journal and may be presented at international conferences. CRD420251011399."

Adverse events • Journal • Retrospective data • CNS Disorders • Depression • Major Depressive Disorder • Mental Retardation • Mood Disorders • Psychiatry • Suicidal Ideation

NORADRENERGIC AND NITRIC OXIDE MODULATORS INFLUENCE ANTIDEPRESSANT EFFECTS OF AGOMELATINE IN MICE (WCN 2025) - "Agomelatine (40 mg/kg), imipramine (10 mg/kg, a tricyclic antidepressant), bupropion (10 mg/kg, dopamine /norepinephrine-reuptake inhibitor), prazosin (1 mg/kg, an α1-adrenoceptor antagonist), yohimbine (1 mg/kg, an α2-adrenoceptor antagonist), and propranolol (2 mg/kg, a β-adrenoceptor antagonist), L-arginine (100 mg/kg, NO precursor), L-NAME (10 mg/kg, NO synthetase inhibitor), methylene blue (5mg/kg, guanylate cyclase inhibitor) were injected 30 min before administration of agomelatine, α-methyl-p-tyrosine (100 mg/kg, an inhibitor of tyrosine hydroxylase) was administered 3 h before agomelatine. Agomelatine proved potential antidepressant effects, that was enhanced by adrenergic or nitric oxide pathway modulation. Further research is warranted to determine the precise molecular mechanisms and optimize clinical applications."

Preclinical • CNS Disorders • Depression • Psychiatry

Improving liver function monitoring in patients initiated on Agomelatine: a six-month retrospective audit in an outpatient psychiatry clinic (ECNP 2025) - "This audit highlights poor compliance with recommended agomelatine liver monitoring protocols in a community outpatient setting. The absence of consistent baseline testing, incomplete follow-up, and lack of patient education documentation collectively represent a significant safety concern. In response, several quality improvement strategies have been introduced to address these gaps, including staff education sessions, implementation of a clear SOP, and incorporation of checklists into clinical workflows to support safer prescribing."

Retrospective data • CNS Disorders • Depression • Major Depressive Disorder • Psychiatry

Brainstorms and blues: the delicate balance of antidepressants in epilepsy (ECNP 2025) - "Serotonin-norepinephrine reuptake inhibitors (SNRIs) can also be considered, although venlafaxine may have a dose-dependent effect on seizure threshold, requiring careful dose titration...Similarly, bupropion, a norepinephrine-dopamine reuptake inhibitor, is generally avoided in patients with epilepsy due to its significant potential to lower the seizure threshold, especially at higher doses. Mirtazapine, an atypical antidepressant that enhances serotonergic and noradrenergic neurotransmission, is often a favorable choice for patients with epilepsy, as it has a low risk of seizure provocation and can also aid with sleep disturbances, which are common in this population. Agomelatine, a melatonin receptor agonist with antidepressant properties, is another option with a favorable safety profile in epilepsy, although its use remains less common compared to SSRIs and SNRIs...Certain enzyme-inducing antiepileptic drugs, such as carbamazepine and phenytoin, can accelerate the..."

CNS Disorders • Depression • Epilepsy • Mood Disorders • Neuralgia • Psychiatry • Sleep Disorder

Beyond mood: a systematic review and network meta-analysis of the physiological and cardiometabolic effects of antidepressants (ECNP 2025) - "Clinically meaningful differences included approximately 4 kg variation in weight change, with significant weight loss observed for agomelatine and marked weight gain for maprotiline. Cardiovascular effects varied notably; nortriptyline increased heart rate by over 21 bpm relative to fluvoxamine, which decreased it...While paroxetine, duloxetine, desvenlafaxine, and venlafaxine decreased body weight, they significantly raised total cholesterol levels, with duloxetine additionally elevating glucose. Liver enzyme elevations were consistently observed with duloxetine, desvenlafaxine, and levomilnacipran, though these were not deemed clinically significant...Healthcare organisations recommend that consideration and discussion of potential side effects should form an integral part of the antidepressant prescribing process (3). Incorporating these differential physiological risks into clinical guidelines can support tailored prescribing decisions, balancing psychiatric..."

Retrospective data • Review • Bipolar Disorder • CNS Disorders • Depression • General Anxiety Disorder • Major Depressive Disorder • Mental Retardation • Mood Disorders • Musculoskeletal Pain • Obsessive-Compulsive Disorder • Post-traumatic Stress Disorder • Psychiatry • Schizophrenia

Investigating the effects of agomelatine and aripiprazole on anxiety-like behavior and cognitive performance in a lipopolysaccharide-induced model of neuroinflammation (ECNP 2025) - "The findings of this study demonstrate that LPS administration increases anxiety-like behavior and impairs learning and memory in animals. Treatment with AGO and ARP effectively attenuated these behavioral deficits. Notably, AGO showed greater efficacy in ameliorating cognitive impairments related to learning and memory, suggesting its potential as a neuroprotective agent in inflammation-induced cognitive dysfunction."

Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Mood Disorders • Psychiatry • TLR4

Redressing long-term antidepressant use in general practice (RELEASE) (ECNP 2025) - "Antidepressants include selective serotonin reuptake inhibitors (sertraline, escitalopram fluoxetine, paroxetine, fluvoxamine and citalopram); serotonin and norepinephrine reuptake inhibitors (venlafaxine, desvenlafaxine, duloxetine); and other antidepressants (mirtazapine, vortioxetine, mianserin, moclobemide, reboxetine, agomelatine). 26 practices and 485 participants randomised. Data collection complete November 2025. Implications: This study will develop new knowledge applicable internationally on the effectiveness, cost-effectiveness, and implementation of the RELEASE multi-strategy intervention in prompting review of antidepressant medication and supporting informed decision-making and safe cessation via hyperbolic tapering to minimise withdrawal symptoms to improve primary mental health care and outcomes for patients."

Alzheimer's Disease • CNS Disorders • Dementia • Mood Disorders • Neuralgia • Psychiatry

Response probability to single intravenous racemic ketamine with psychopharmacological combinations: a pooled post-hoc study (ECNP 2025) - "The combination of ketamine with antidepressants that block 5-HT2A receptors (such as mirtazapine, mianserine, trazodone, and agomelatine; n = 41) significantly increased the response rate to 58.5%, compared to 28.9% in those who did not receive these combinations. In contrast, combining ketamine with serotonin reuptake inhibitors (escitalopram, fluoxetine, paroxetine, sertraline, vortioxetine; n = 34) or with antipsychotics characterized by higher D2 than 5-HT2A blockade (amisulpride, aripiprazole, cariprazine; n = 10) significantly reduced the response rate to 26.5% and 0%, respectively, compared to 53.8% and 48.7% in those not receiving these combinations. Combination of ketamine with serotonin and norepinephrine reuptake inhibitors (clomipramine, venlafaxine, duloxetine, milnacipran; n = 30) or with antipsychotics (n = 40), compared to ketamine without SNRIs or without antipsychotics, did not significantly alter the probability of response (p = 0.369 and p = 0.083,..."

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

Efficacy and acceptability of pharmacological interventions for insomnia in patients with severe mental illness: A systematic review and meta-analysis (ECNP 2025) - "The most frequently studied drugs were agomelatine (RCTs=3, n=686), eszopiclone (RCTs=3, n=599), and zolpidem (RCTs=3, n=601). Despite their frequent use, many pharmacological interventions for insomnia have never been investigated in patients with SMI. The studies that provided sufficient data for meta-analysis showed better efficacy with similar acceptability compared to placebo, but the generalizability of these results is limited by the high heterogeneity and low quality of the included studies. This underscores the need for high-quality RCTs to provide a better scientific basis for the pharmacological treatment of insomnia in SMI."

Retrospective data • Review • Bipolar Disorder • CNS Disorders • Depression • Insomnia • Major Depressive Disorder • Mood Disorders • Psychiatry • Schizophrenia • Sleep Disorder

Anhedonia as focus to reduce symptom heterogeneity of depression (ECNP 2025) - "Drugs such as vortioxetine, agomelatine, bupropion, ketamine, and brexpiprazole show promising anti-anhedonic effects, while traditional antidepressants such as SNRIs and, even more, SSRIs are less effective...Innovative treatments such as aticaprant and psilocybin showed promising results. Substantial evidence suggests that improving anhedonia leads to better psychosocial functioning, quality of life, and sustained remission. No conflict of interest"

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

THE PHYSIOLOGICAL AND CARDIOMETABOLIC EFFECTS OF ANTIDEPRESSANTS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS (WPA-WCP 2025) - "Clinically meaningful differences included approximately 4kg variation in weight change, with significant weight loss observed for agomelatine and weight gain for maprotiline. Nortriptyline increased heart rate by over 21 bpm relative to fluvoxamine, which decreased it...While paroxetine, duloxetine, desvenlafaxine, and venlafaxine decreased body weight, they significantly raised total cholesterol levels, with duloxetine additionally elevating glucose...Conclusions Our findings highlight clinically relevant variations in adverse effects across antidepressants, particularly cardiometabolic parameters. Incorporating these physiological risks into practice can support tailored prescribing decisions, balancing psychiatric efficacy with patient-specific physical health considerations and preferences."

Retrospective data • Review • CNS Disorders • Mental Retardation • Psychiatry