agomelatine / Generic mfg. - LARVOL DELTA

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

The Therapeutic Potential of Melatonin and Its Novel Synthetic Analogs in Circadian Rhythm Sleep Disorders, Inflammation-Associated Pathologies, and Neurodegenerative Diseases. (PubMed, Med Res Rev) - "In this review, we explore melatonin and its receptors and provide an updated overview on research concerning the role of melatonin, either as an endogenous molecule or as a drug, in: sleep-wake cycle regulation; circadian rhythms; inflammatory processes that may compromise cardiovascular, respiratory, gastrointestinal, renal, and reproductive system functions; and neurodegenerative disorders such as Alzheimer's and Parkinson's disease. The most recent and promising research findings concerning melatonin synthetic analogs such as agomelatine and ramelteon are highlighted, pointing toward new compounds with promising pharmacological activity while emphasizing their structural differences and advantages when compared to melatonin."

Journal • Review • Alzheimer's Disease • Cardiovascular • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • Sleep Disorder • Sleep Wake Cycle Disorder • CLOCK

Agomelatine Alleviates Depressive-like Behaviors by Suppressing Hippocampal Oxidative Stress in the Chronic Social Defeat Stress Model. (PubMed, Antioxidants (Basel)) - "Additionally, agomelatine attenuated mitochondrial dysfunction and restored synaptic plasticity, as evidenced by an increased density of excitatory synapses and enhanced neuronal activity. These findings suggest that agomelatine may exert therapeutic effects by reducing oxidative stress, preserving mitochondrial function, and enhancing synaptic plasticity, providing new insights into its potential as a treatment for chronic social defeat stress-induced depression."

Journal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Depression • Major Depressive Disorder • Mental Retardation • Metabolic Disorders • Mood Disorders • Psychiatry

Resting EEG source-level connectivity pattern to predict anhedonia improvement with agomelatine treatment in patients with major depression. (PubMed, J Affect Disord) - "Global topological properties of source-level EEG FC can predict anhedonia improvement during antidepressant treatment, which might help guide treatment decisions and advance precision psychopharmacology."

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

Carbon Materials in Voltammetry: An Overview of Versatile Platforms for Antidepressant Drug Detection. (PubMed, Micromachines (Basel)) - "Moreover, the combination of voltammetric approaches with the unique characteristics of carbon and its derivatives has led to the development of powerful electrochemical sensing tools for detecting antidepressant drugs, which are highly desirable in healthcare, environmental monitoring, and the pharmaceutical industry. In this review, carbon-based materials, such as glassy carbon and boron-doped diamond, and a wide spectrum of carbon nanoparticles, including graphene, graphene oxides, reduced graphene oxides, single-walled carbon nanotubes, and multi-walled carbon nanotubes were described in terms of the sensing performance of agomelatine, alprazolam, amitriptyline, aripiprazole, carbamazepine, citalopram, clomipramine, clozapine, clonazepam, desipramine, desvenlafaxine, doxepin, duloxetine, flunitrazepam, fluoxetine, fluvoxamine, imipramine, nifedipine, olanzapine, opipramol, paroxetine, quetiapine, serotonin, sertraline, sulpiride, thioridazine, trazodone, venlafaxine,..."

Journal • Review • CNS Disorders • Depression • Mood Disorders • Personality Disorder • Psychiatry

Pharmacological Monotherapy for Depressive Disorders: Current and Future-A Narrative Review. (PubMed, Medicina (Kaunas)) - " The STAR*D Study demonstrated that sertraline, venlafaxine, and bupropion monotherapy had similar efficacy in patients with major depressive disorder (MDD) who failed citalopram. A network meta-analyses of randomized, placebo-controlled trials found that SSRIs, SNRIs, bupropion, TCAs, mirtazapine, and agomelatine had similar relative efficacy compared to placebo, but had different acceptability. Gepirone had more failed/negative studies and smaller effect size relative to placebo compared to other antidepressants. The combination of dextromethorphan and bupropion, ketamine infusion, and intranasal esketamine had faster onset of action but similar effect size compared to monoamine-based antidepressants as monotherapy. Brexanolone and zuranolone are effective in postpartum depression (PPD), but the effect size of zuranolone in MDD as monotherapy or adjunctive therapy was very small...NMDA receptor antagonists and neurosteroid antidepressants will play a bigger role with..."

Journal • Monotherapy • Review • CNS Disorders • Depression • Major Depressive Disorder • Mood Disorders • Postpartum Depression • Psychiatry

Agomelatine attenuates Dexamethasone-Induced Neurotoxicity in Rats Through the activation of MT1/2 receptors and attenuation of oxidative stress. (PubMed, Eur J Pharmacol) - "Previous studies showed that agomelatine ameliorates doxorubicin-induced brain injury in rats...Subcutaneous injections of dexamethasone (10 mg/kg, 4 days) were used to induce neurotoxicity in rats...Luzindole prior administration to agomelatine reversed the protective effects of agomelatine except its effect on lipid peroxidation. Collectively, these findings suggest that agomelatine can protect against dexamethasone-induced neurotoxicity partially by activating melatonin receptors in addition to exerting antioxidant effects."

Journal • Preclinical • Alzheimer's Disease • Cardiovascular • CNS Disorders • Psychiatry • Reperfusion Injury • Vascular Neurology • GFAP

The association between anhedonia and prefrontal cortex activation in patients with major depression: a functional near-infrared spectroscopy study. (PubMed, Eur Arch Psychiatry Clin Neurosci) - "This study investigated cerebral blood flow characteristics using functional nearinfrared spectroscopy (fNIRS) in agomelatine-treated depressed patients with anhedonia...Furthermore, the increased oxy-hemoglobin (oxy-Hb) values from the baseline to the one week after treatment was positively related to the total MADRAS 5-item score reductions in the left-hemispheric orbitofrontal cortex (r = - 0.307, p = 0.005). Our findings suggest that abnormal functional connectivity over OFC may reflect the pathophysiological characteristics of anhedonia and serve as a clinical biomarker for anhedonia."

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

Nasal In-Situ Gels of Brij®-Enriched Novasomes as Optimistic Nanovesicular Carriers for Enhancing Anti-Depressant Action of Agomelatine. (PubMed, AAPS PharmSciTech) - "Rats treated with nasal optimal NVG9 manifested increased sucrose preference (SP) percent (80.73%) and levels of dopamine (50.42 ng/g) and serotonin (44.92 ng/g) with decreased low latency time values (5.86 min). This study confirmed the in-vivo safety and amplification of precognitive and anti-depressant action of agomelatine after intranasal administration."

Journal

Efficacy of Add-On Agomelatine on Agitation, Aggression, and Neuroprotection in Alzheimer's Disease: A Randomized, Blinded, Controlled Trial. (PubMed, Am J Geriatr Psychiatry) - "A daily dose of 12.5 mg agomelatine may effectively and safely reduce agitation and aggression in patients with AD when used as an add-on therapy. However, further studies with larger samples and extended durations are needed to definitively confirm agomelatine's role in managing BPSD in AD."

Journal • Alzheimer's Disease • CNS Disorders • Dementia • BDNF

Efficacy and tolerability of antidepressants in individuals suffering from physical conditions and depressive disorders: network meta-analysis. (PubMed, Br J Psychiatry) - "Antidepressants are effective in individuals with comorbid physical conditions, although tolerability is a relevant concern. Selective serotonin reuptake inhibitors (SSRIs) have the best benefit-risk profile, making them suitable as first-line treatments, while tricyclics are highly effective but less tolerated than SSRIs and placebo."

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

Minimizing STOPP and Beers Criteria Risks in PIM Treatments Using PM-TOM and ChatGPT: A Case Study. (PubMed, Stud Health Technol Inform) - "She was initially prescribed acetaminophen, alendronate, omeprazole, lisinopril, metoprolol, aspirin, citalopram, and vitamin D, which were assessed as inadequate...In the optimized treatment, omeprazole (PPI) was replaced with famotidine (H2-blocker), citalopram (SSRI) with agomelatine (atypical antidepressant), zoledronic acid (bisphosphonate) with denosumab (RANK ligand inhibitor), aspirin (NSAID) with ticagrelor (antiplatelet), and lisinopril with benazepril (ACE inhibitor)...Finally, ChatGPT validated the proposed adjustments, confirming their alignment with the guidelines and highlighting the potential for longer-term benefits. This case study illustrates how a combined use of PM-TOM and AI tools can effectively support the clinical decision-making process by optimizing polypharmacy treatments and minimizing their PIMs, major contributors to morbidity in older adults and high healthcare costs."

Journal • Cardiovascular • CNS Disorders • Coronary Artery Disease • Depression • Gastroesophageal Reflux Disease • Heart Failure • Hypertension • Immunology • Osteoarthritis • Osteoporosis • Pain • Psychiatry • Rheumatology

High-performance liquid chromatography-tandem mass spectrometry for simultaneous determination of 23 antidepressants and active metabolites in human serum and its application in therapeutic drug monitoring. (PubMed, Front Pharmacol) - "In this paper, we developed a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to study simultaneously TDM and clinical pharmacokinetics of 23 antidepressants and active metabolites: sertraline, escitalopram, fluvoxamine, paroxetine, duloxetine, milnacipran, fluoxetine, venlafaxine, O-desmethylvenlafaxine, mirtazapine, trazodone, bupropion, hydroxybupropione, norfluoxetine, vortioxetine, agomelatine, mianserin, doxepine, desmethyldoxepin, clomipramine, desmethylclomipramine, amitriptyline and nortriptyline hydrochloride...Validation of the developed method was carried out based on the Chinese Pharmacopoeia guidelines for bioanalytical method validation, including assessment of specificity, calibration curves, carryover, accuracy, crosstalk, precision, stability, recovery, dilution integrity and matrix effect. The results showed that a simple, fast, reliable and specific HPLC'MS/MS method was developed and validated, and all the..."

Journal • CNS Disorders • Depression • Psychiatry

Global burden of antidepressant-associated seizures from 1967 to 2023: A comparative analysis of the international pharmacovigilance database. (PubMed, J Affect Disord) - "Our findings align with earlier studies indicating that SNRIs and SSRIs carry a lower risk of seizures, whereas bupropion and clomipramine are linked to a higher risk. Agomelatine, vortioxetine, and SNRIs like desvenlafaxine and duloxetine may potentially be safe alternatives."

Adverse events • Journal • CNS Disorders • Epilepsy

The protective role of melatonin and agomelatine against oxidative stress following laparoscopic ovariectomy in dogs. (PubMed, BMC Vet Res) - "The results of this study demonstrate that melatonin, by increasing total antioxidant capacity, and agomelatine, through enzymatic antioxidant pathways, contributed to the reduction of free radical levels in dogs. The present study revealed that administering agomelatine (0.3 mg/kg/day, p.o) could decrease MDA levels significantly after laparoscopic ovariectomy up to day 3."

Journal • CAT

Circadian antidepressant treatments in depression: A systematic review and meta-analysis. (PubMed, Chronobiol Int) - "The optimal time of maximum efficacies in 5 out of 15 drugs in the 10 studies was at zeitgeber time (ZT) 2, including fluoxetine, sertraline, citalopram, doxepin, and agomelatine. The best therapeutic effects of mirtazapine, trazodone, and agomelatine were at ZT10, while maximum efficacies of venlafaxine and fluvoxamine were at ZT6 and ZT13, respectively...More prospective randomized trials or randomized experiments are demanded to establish recommendations for optimal circadian timing of depression based on zeitgeber time. It would be of interest to further evaluate this time-selection as a potential viable novel therapeutic in future research."

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