The effects of agomelatine in cisplatin-induced toxicity on the kidney and liver tissues: In vivo study

Abstract Nephrotoxicity and hepatotoxicity are frequently seen adverse effects during cisplatin chemotherapy. In this study, we investigated the effects of agomelatine on cisplatin-induced toxicity in the kidney and liver. Animals were administered with a single dose of cisplatin (7 mg/kg, i.p.) and treated with agomelatine (20 and 40 mg/kg, p.o) for seven days. Renal and hepatic functions were evaluated by measuring concentrations of creatinine, BUN, AST and ALT in the serum. Oxidative stress and protein peroxidation were assessed by measuring SOD, CAT, GSH and AOPP levels in both tissues. Serum PON-1 levels were also evaluated. Histopathological analysis was performed to determined structural changes in the kidney and liver. Agomelatine (20 mg/kg) treatment approximately halved cisplatin-related increase in serum creatinine, BUN, AST and ALT levels. Agomelatine (20 mg/kg) significantly prevented the cisplatin-induced excessive decrease in SOD, CAT, GSH in both tissues and serum PON-1 levels. Agomelatine (20 and 40 mg/kg) protected the structural integrity of the kidney against cisplatin-insult. Although agomelatine (40 mg/kg) protected the kidney and showed parallel results with 20 mg/kg biochemically, it failed to show the same liver tissue effects in both analyses. Although agomelatine protected against cisplatin-induced toxicity in the kidney and liver, care should be taken with higher doses for possible hepatotoxicity.

Research progress on antidepressant effects of melatonin and its receptor agonists / 中国药理学通报

Depression, a chronic syndrome with significant and lasting depression and sleep disturbance, is the most common mental disorder.Recent studies have shown that melatonin plays an important role in the occurrence and development of depression.rI1iis review describes the antidepressant effects of melatonin from HPA axis, cytokines, neurosynaptic plasticity and monoamine neurotransmitters, and summarizes the melatonin receptor agonists agomelatine, ramelteon and piromelatine antidepressant effects.A theoretical basis is expected to provide a reference for the study of melatonin's antidepressant mechanism.

Efficacy and safety of the combination of agomelatine and low-dose olanzapine in 184 cases of postprandial distress syndrome with depression, anxiety and sleep disorders / 中华消化杂志

Objective:To observe the efficacy and safety of the combination of agomelatine and low-dose olanzapine (AO) in the treatment of postprandial distress syndrome (PDS) with depression, anxiety and sleep disorders.Methods:From April 2019 to September 2020, PDS patients with depression, anxiety and sleep disorders in Tianjin Medical University General Hospital were selected and divided into AO group and flupentixol-melitracen (FM) group. Patients of the AO group were given oral agomelatine 25 mg and AO 1.70 mg (both once per day), and the patients of FM group were given oral FM 10.5 mg (once per day), and all patients took itopride 50 mg (three times per day) at the same time. The total treatment course was eight weeks. Nepean dyspepsia index-symptom (NDIS), patient health questionnaire-9 (PHQ-9), generalized anxiety disorder-7 (GAD-7) and Pittsburgh sleep quality index (PSQI) were used to evaluate the gastrointestinal symptoms, depression, anxiety and sleep disorders before treatment and two, four and eight weeks after treatment, respectively. The efficacy was evaluated according to the changes of scores of gastrointestinal symptoms before and after treatment. The adverse effects after medication were recorded. Independent sample t test and chi-square test were used for statistical analysis. Results:A total of 184 PDS patients with depression, anxiety and sleep disorders were enrolled, including 98 patients in AO group and 86 patients in FM group. At two, four and eight weeks after treatment, NDIS, PHQ-9, GAD-7 and PSQI scores of AO group and FM group were all lower than those of each group before treatment (AO group: 13.73±0.53, 10.13±0.44 and 7.87±0.31 vs. 27.08±0.84; 6.04±0.35, 4.70±0.31 and 3.81±0.22 vs. 10.04±0.50; 6.36±0.30, 5.29±0.28 and 4.21±0.19 vs. 10.71±0.51; 6.64±0.37, 5.27±0.35 and 4.09±0.30 vs. 11.14±0.42; FM group: 15.33±0.58, 11.58±0.50 and 9.80±0.35 vs. 25.10±0.79; 6.79±0.35, 5.71±0.32 and 4.86±0.30 vs. 9.11±0.46; 7.27±0.31, 6.51±0.32 and 5.21±0.27 vs. 9.79±0.44; 8.01±0.33, 6.76±0.32 and 5.78±0.32 vs. 10.44±0.32), and the differences were statistically significant (AO group: tNDIS=13.470, 17.930 and 21.530, tPHQ-9=6.488, 8.991 and 11.300, tGAD-7=7.361, 9.315 and 11.031, tPSQI=7.088, 9.736 and 12.550. FM group: tNDIS=9.921, 14.400 and 17.640, tPHQ-9=4.032, 6.106 and 7.781, tGAD-7=4.638, 5.993 and 8.840, tPSQI=5.289, 8.199 and 10.310, all P<0.05). At two, four and eight weeks after treatment, NDIS, GAD-7 and PSQI scores of AO group were all lower than those of the FM group during the same period (NDIS: 13.73±0.53 vs. 15.33±0.58, 10.13±0.44 vs. 11.58±0.50, 7.87±0.31 vs. 9.80±0.35; GAD-7: 6.36±0.30 vs. 7.27±0.31, 5.29±0.28 vs. 6.51±0.32, 4.21±0.19 vs. 5.21±0.27; PSQI: 6.64±0.37 vs. 8.01±0.33, 5.27±0.35 vs. 6.76±0.32, 4.09±0.30 vs. 5.78±0.32), and the differences were statistically significant ( tNDIS=2.018, 2.225 and 4.156, tGAD-7=2.097, 2.869 and 2.536, tPSQI=1.951, 2.359 and 3.099, all P<0.05). At eight weeks after treatment, the total effective rate of the AO group was higher than that of the FM group (94.9%, 93/98 vs. 84.9%, 73/86), and the difference was statistically significant ( χ2=5.205, P=0.026). The incidence of adverse reactions of constipation and somnolence of the AO group were both lower than those of the FM group (2.0%, 2/98 vs. 9.3%, 8/86 and 1.0%, 1/98 vs. 8.1%, 7/86, respectively), and the differences were statistically significant ( χ2=4.699 and 5.582, P=0.047 and 0.027). Conclusion:AO may be a treatment option for PDS with depression, anxiety and sleep disorders.

Anxiolytic properties of compounds that counteract oxidative stress, neuroinflammation, and glutamatergic dysfunction: a review

Objective: Anxiety disorders are highly prevalent and the efficacy of the available anxiolytic drugs is less than desired. Adverse effects also compromise patient quality of life and adherence to treatment. Accumulating evidence shows that the pathophysiology of anxiety and related disorders is multifactorial, involving oxidative stress, neuroinflammation, and glutamatergic dysfunction. The aim of this review was to evaluate data from animal studies and clinical trials showing the anxiolytic effects of agents whose mechanisms of action target these multiple domains. Methods: The PubMed database was searched for multitarget agents that had been evaluated in animal models of anxiety, as well as randomized double-blind placebo-controlled clinical trials of anxiety and/or anxiety related disorders. Results: The main multitarget agents that have shown consistent anxiolytic effects in various animal models of anxiety, as well in clinical trials, are agomelatine, N-acetylcysteine (NAC), and omega-3 fatty acids. Data from clinical trials are preliminary at best, but reveal good safety profiles and tolerance to adverse effects. Conclusion: Agomelatine, NAC and omega-3 fatty acids show beneficial effects in clinical conditions where mainstream treatments are ineffective. These three multitarget agents are considered promising candidates for innovative, effective, and better-tolerated anxiolytics.

Effect of agomelatine on psychomotor function tests in healthy human volunteers

Background: Agomelatine is a melatonergic agonist that acts specifically on MT1/MT2 melatonergic receptors and 5-HT2C antagonism. The present study was taken up to evaluate the effect of Agomelatine 25mg on psychomotor function in healthy human volunteers.Methods: The effect of Agomelatine was studied in 12 healthy volunteers of either gender. The study was a randomised, cross over, placebo controlled study, done after obtaining permission from NIMS Institutional Ethics Committee and informed consent taken from all the subjects, after briefly explaining the study procedure and training them adequately. Psychomotor function was assessed using Choice reaction time (CRT), Critical Flicker fusion test (CFFT), Digit letter substitution test (DLST), Six letter cancellation test (SLCT), Card sorting test (CST) and Visual analog scale (VAS). Psychomotor function tests were performed, 90 minutes after administering Agomelatine 25 mg or placebo. Washout period of seven days was allowed between the cross over. Statistical analysis was done by comparing groups using unpaired t test.Results: There was significant decrease in the mean percentage of time (p<0.01) in CRT in Agomelatine group (20.09±9.47%) when compared to placebo (10.48±3.68%). Improved mean percentage of performance was seen in CFFT with Agomelatine (6.2±2.1%) compared to placebo (9.11±2.99%). No significant difference was noted in the performance of DLST, SLCT and CST. Drug was subjectively rated as sedative on VAS.Conclusions: There is no significant effect of Agomelatine on psychomotor performance. CNS processing of information also improved. Agomelatine can thus be safely administered to depressed patients.

Effect of agomelatine on memory impairment and ERK5 expression in hippocampus of rats with posttraumatic stress disorder / 中华行为医学与脑科学杂志

Objective To investigate the effect of agomelatine on memory impairment and expres-sion of extracellular signal-regulated kinase 5 (ERK5) in post-traumatic stress disorder ( PTSD)-like rats. Methods Forty-eight SD rats were divided into control group (SHAM group),post-traumatic stress disorder group (PTSD group),agomelatine group (AGO group) and placebo control group(PC group) according to random number table with 12 in each group. The PTSD-like model was established by internationally recog-nized single prolonged stress (SPS) stimulation,and the AGO group and PC group were given the same a-mount of agomelatine and saline respectively by intragastric administration within 8 hours after modeling for 14 days. The arousal emotional level and learning and memory ability of rats were observed by open field ex-periment and Morris water maze test. Then the expressions of ERK5 and ERK5 mRNA in hippocampus of rats were detected by Western blot and qRT-PCR. Results (1) The results of the open field experiment showed that compared with the SHAM group (38. 58±5. 76),the numbers of crossing the grids of the PTSD group (29. 75±3. 75) decreased (P<0. 01). Compared with the PC group (28. 58±2. 91),the number of crossing the grids of the AGO group (41. 00±4. 49) increased (P<0. 01). (2) In Morris water maze test, positioning navigation experiment showed that compared with the SHAM group, the escape latency of the PTSD group and the PC group increased (P<0. 01),while the escape latency of AGO group was shorter than that of the PC group (P<0. 01). And in the space exploration experiment,compared with the SHAM group (2. 12±0. 51),the times of crossing the platform in PTSD group (1. 03±0. 43) and the PC group (1. 23± 0. 59) decreased (P<0. 01),while the times of crossing the platform in AGO group (2. 75±0. 72) increased compared with PC group (P<0. 01). Compared with SHAM group (12. 14±2. 53),the latency of crossing the platform of PTSD group (27. 33±6. 54) increased (P<0. 01),and the agomelatine group (14. 36±4. 27) de-creased compared with the PC group (29. 67±9. 72) (P<0. 01). (3) Results of Western blot and qRT-PCR showed compared with the SHAM group,the levels of ERK5 and ERK5 mRNA in rat hippocampus were up-regulated in the PTSD group (P<0. 01),and the expression of ERK5 and ERK5 mRNA was higher than that of PC group (P<0. 01). Conclusion Agomelatine can effectively improve the learning and memory ability of PTSD-like rats,which may be related to the up-regulation of ERK5 protein expression in hippocampal tis-sues.

Clinical observation of conventional antipsychotics combined with agomelatine in schizophrenia patients with obsessive-compulsive symptoms / 中国神经精神疾病杂志

Objective To examine the efficacy, safety, economic benefits and social function of conventional antipsychotics combined with agomelatine in the treatment of schizophrenia patients with obsessive-compulsive symptoms. Methods Eighty schizophrenic patients with obsessive-compulsive symptoms were randomly divided into two groups. The study group was treated with conventional antipsychotic drugs combined with agomelatin, and the control group combined with clomipramine for 8 weeks. Positive and negative symptom scale (PANSS) and Yale-Brown obsessive-compulsion scale (Y-BCOS) were used to evaluate the symptoms at before treatment, at discharge and one month after discharge. Social disability screening scale (SDSS), treatment emergent symptom scale (TESS) and the economic benefits was used to evaluate the social function, treatment efficacy and economic status. Results Before treatment, there was no significant difference in the scores of each scale between the two groups (P＞0.05). There was no significant difference in PANSS scores between the two groups at all time points (P＞0.05). The difference between Y-BCOS score and pre-treatment value was higher in the study group than in the control group (P<0.05). The difference between SDSS score and pre-treatment value was higher in the study group than in the control group (P<0.05). The TMRs were lower in the study group than in the control group at one month after discharge (P<0.05). The TESS score was lower in the study group than in the control group at discharge and one month after discharge. The cost and income were higher and the cost-effect ratio was lower in the study group than in the control group at one month after discharge (P<0.05). PANSS and Y-BCOS were positively correlated with TMR, SDSS and CER (P<0.05), but not with TESS at one month after discharge (P＞0.05). TESS was positively correlated with TMR, SDSS and CER (P<0.05). Conclusion The treatment of conventional antipsychotics combined with agomelatine in schizophrenia patients with obsessive-compulsive symptoms are safe and effective. Patients can achieve better social function, good economic and social benefits.

A meta-analysis of safety of agomelatine and SSRIs for depression / 中华行为医学与脑科学杂志

Objective To compare the safety of agomelatine and selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression.Methods Retrieved literatures in the database at home and abroad from the built of the databases to March in 2016.The databases included Pubmed,Cochrance library,CNKI,Wanfang database and VIP database.Two researchers selected literatures,evaluated quality and extracted data independeatly.5.3.5 RevMan software was used to analyze.Result 87 literatures were retrieved,and nine English literatures and two Chinese literatures were included.Agomelatine had a lower risk than paroxetine in insomnia (RR:0.40,95％ CI:[0.17,0.92],P=0.03) and sexual dysfunction (RR:0.13,95％ CI:[0.04,0.39],P=0.0003),than fluoxetine(RR:0.68,95％ CI:[0.48,0.96],P=0.03) and paroxetine(RR:0.37,95％ CI:[0.25,0.55],P＜0.01) in nausea and vomiting,and than escitalopram in sweating(RR:0.34,95％ CI:[0.13,0.85],P=0.02) and headaches(RR:0.63,95％ CI:[0.43,0.91],P=0.01).The difference of them was statistically significant.Agomelatine had a higher risk than sertraline (RR:4.65,95％ CI:[1.02,21.16],P=0.05) in drowsiness,and than escitalopram in constipation (RR:3.46,95％ CI:[1.16,10.36],P=0.03),the difference was statistically significant too.Compared agomelatine and SSRIs,the occurrence risk of dry mouth and diarrhea were no significant difference.Conclusion Both agomelatine and selective serotonin reuptake inhibitors (SSRIs) had its pros and cons in terms of safety.Safety of agomelatine is better than paroxetine.Agomelatine and escitalopram had its own advantages and disadvantages respectively in safety.The evidence of the safety among agomelatine,fluoxetine and sertraline need further explore.

Agomelatine versus Sertraline: An Observational, Open-labeled and 12 Weeks Follow-up Study on Efficacy and Tolerability

OBJECTIVE: In this open-labeled, 12 weeks follow-up study, we aimed to compare the efficacy and tolerability of agomelatine with sertraline. METHODS: The outpatients of adult psychiatry clinic who have a new onset of depression and diagnosed as ‘major depressive episode’ by clinician according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition and prescribed agomelatine (25 mg/day) or sertraline (50 mg/day) were included in the study. RESULTS: The decline of mean Montgomery-Asberg Depression Rating Scale (MADRS) scores of agomelatine group was significantly higher than the sertraline group at the end of 2nd week; however, the difference was not significant at the end of 3 months. Mean Clinical Global Impression-Improvement scale (CGI-I) scores of agomelatine group was lower than sertraline group at first week. Mean CGI-Severity scale and CGI-I scores were favour to sertraline group at the end of the study. Remission rates were 46.7% for sertraline group and 33.3% for agomelatine group while response rates were 76.7% for both groups. Any patient from agomelatine group dropped-out due to adverse effects. The amount of side effects was also less with agomelatine. CONCLUSION: Agomelatine has a rapid onset efficacy on depressive symptoms and this can be beneficial for some critical cases. Considering MADRS scores, agomelatine seems to have similar efficacy with sertraline but we also point the need for long term studies since CGI scores were favour to sertraline group at the end of the study. Agomelatine has a favourable tolerability profile both in terms of discontinuation and the amount of side effects compared to sertraline.

Implementation of a reference-scaled average bioequivalence approach for highly variable generic drug products of agomelatine in Chinese subjects

The aim of this study was to apply the reference-scaled average bioequivalence (RSABE) approach to evaluate the bioequivalence of 2 formulations of agomelatine, and to investigate the pharmacokinetic properties of agomelatine in Chinese healthy male subjects. This was performed in a single-dose, randomized-sequence, open-label, four-way crossover study with a one-day washout period between doses. Healthy Chinese males were randomly assigned to receive 25 mg of either the test or reference formulation. The formulations were considered bioequivalent if 90% confidence intervals (CIs) for the log-transformed ratios and ratio of geometric means (GMR) of AUC and C max of agomelatine were within the predetermined bioequivalence range based on RSABE method. Results showed that both of the 90% CIs for the log-transformed ratios of AUC and C max of 7-desmethyl-agomelatine and 3-hydroxy-agomelatine were within the predetermined bioequivalence range. The 90% CIs for natural log-transformed ratios of C max, AUC0-t and AUC0-∞ of agomelatine (104.42-139.86, 101.33-123.83 and 97.90-117.94) were within the RSABE acceptance limits, and 3-hydroxy-agomelatine (105.55-123.03, 101.95-109.10 and 101.72-108.70) and 7-desmethyl-agomelatine (104.50-125.23, 102.36-111.50 and 101.62-110.64) were within the FDA bioequivalence definition intervals (0.80-1.25 for AUC and 0.75-1.33 for C max). The RSABE approach was successful in evaluating the bioequivalence of these two formulations.

A reliable crystallization process for the preparation of agomelatine form I / 中国药科大学学报

@#A reliable crystallization process was developed for the preparation of stable agomelatine form I. This antisolvent crystallization was explored in ethanol-n-heptane by adding PVP and ethanol-water system by adding HPMC, respectively. Factors such as solvent, polymer, concentration of polymer, and solvent ratio were subjected to detailed examination. Accelerated and long-term stability observations indicates that the presence of polymeric additives in the crystallization process enhances the stability of agomelatine form I.

Systematic Review of the Efficacy of Agomelatine in the Treatment of Depression in Acute Phase / 中国药房

OBJECTIVE:To systematically review the efficacy of agomelatine in the treatment of depression in acute phase, and provide evidence-based reference for the clinical treatment. METHODS:Retrieved from Cochrane Library,Medline,EMBase, CJFD,VIP,CBM,Wanfang Database,WHO Clinical Trials Registry Platform and American Clinical Trials Registry Platform, the randomized controlled trials (RCT) about agomelatine versus placebo in the depression patients in acute phase. After quality evaluation and data extraction,Meta-analysis was conducted by using Rev Man 5.2 statistics software. RESULTS:A total of 7 RCT were included,involving 2 378 patients. Results of Meta-analysis showed the effective rate in agomelatine group was obviously bet-ter than placebo group [RR=1.43 ,95%CI(1.29 ,1.59),P<0.001] ,remission rate was obviously better than placebo group [RR=1.27 ,95%CI(1.03 ,1.57),P=0.02] ,and the endpoint score of depression scales was obviously lower than placebo group [MD=-2.92,95%CI(-3.65,-2.20),P<0.001],there was statistically significance. CONCLUSIONS:Agomelatine is effective in the treatment of depression patients in acute phase. However,due to the limit of methodological quality and sample size,it remains to be further verified with more rigorously designed and long-term follow-up of large-scale RCT.

Determination of Trace Nickel in Agomelatine by Inductive Coupled Plasma Atomic Emission Spectrometry / 中国药师

Objective:To establish a method for the determination of trace nickel in agomelatine. Methods:An inductive coupled plasma atomic emission spectrometry method was applied in the determination at 221. 648 nm. The sample solution was prepared by the ignited residue of agomelatine. The content of nickel was determined using the standard curve. Results:The linear range was 0. 025-1. 000 μg·ml-1(r=0. 999 8). The RSD of precision was 0. 63%. The detection limit was 0. 000 8μg·ml-1. The quantitative limit was 0. 003μg·ml-1 . The average recovery was 99. 4% with RSD of 2. 20%. The RSD of repeatability was 1. 33%. Conclusion:The method is simple, sensitive and accurate in the determination of trace nickel in agomelatine.

Agomelatine: The Novel Antidepressant / 대한정신약물학회지

Major depression is a common mental illness, associated with high morbidity and mortality. Antidepressants have been the first-line therapies due to their confirmed efficacy, however, considering high rate of poor treatment response to these therapies, distressing side effects, and delayed onset of their efficacy, there has been much effort to find alternative treatments for major depression. Recently, evidence regarding disturbed circadian rhythms involved in the pathophysiology of major depression has emerged, the interest on this area has been increasing. Agomelatine is an emerging antidepressant, with a unique profile of selective antagonist at serotonin 2C (5-HT2C) receptors and melatonin receptor agonist. Previous studies have shown its superior efficacy over placebo in treating major depression. Previous trials have shown comparable antidepressant efficacy of agomelatine compared to other standard antidepressants including venlafaxine, sertraline, and fluoxetine. Regarding safety profile of agomelatine, it seems to be not associated with sexual dysfunction and it has less potential for serotonin syndrome or discontinuation syndrome than standard antidepressants including selective serotonin reuptake inhibitors. Considering favorable results on the efficacy and safety of agomelatine in treating depression, it could be a good, safe treatment alternative in the treatment of depression.

Agomelatine versus sertraline for the treatment of elderly patients with post-stroke depression: a randomized, double-blind, controlled trial / 国际脑血管病杂志

Objeetive To investigate the effectiveness and safety of agomelatine for the treatment of elderly patients with post-stroke depression.Methods A total 80 elderly patients with post-stroke depression were randomly divided into either an agomelatine group or a sertraline group.The Hamilton Depression Scale (HAMD),National Institutes of Health Stroke Scale (NIHSS) and Barthel Index were used to evaluate the patients before and after 1,2,4,and 6 weeks,respectively.Results HAMD,NIHSS,and Barthel index scores were improved significantly after treatment in the agomelatine group (n =38) and the sertraline group (n =42).There were significant improvement in the scores of HAMD,NIHSS and Barthel Index with time in both groups (all P ＜0.001).There were no significant difference in the scores of HAMD and NIHSS at different time points after treatment between the agomelatine group and the sertraline group,and the Barthel Index scores began to have significance difference from the fourth week after treatment (all P ＜ 0.05).Conclusions The efficacy of agomelatine for the treatment of PSD is almost the same as sertraline,and the effect of improving activities of daily living is better than sertraline.The safety of both agomelatine and sertraline is good.

Evaluation and preparation of agomelatine orally disintegrating tablets / 国际药学研究杂志

Objective To prepare the agomelatine orally disintegrating tablets (AGO-ODT) and evaluate their quality. Methods The AGO-hydroxypropyl-(β-cyclodextrin inclusion complex was prepared by saturated water solution method, and then mixed with auxiliary materials and compressed into ODT. The disintegration, dissolution and acceptability of the ODT were evaluated, and AGO content was measured by the HPLC method. Results The mean disintegration time of AGO-ODT was 13. 17 s and the cumulative dissolution was higher than 95% at 8 minutes. The taste, swallowing and feeling of AGO-ODT were desirable. In addition, good linearity was obtained between chromatographic peak area and AGO concentration in the range of 1.0-40.0 (μg/ml, and the recovery was between 98%-102% with the RSD less than 2%. Conclusion The disintegration and dissolution of prepared AGO-ODT work well. The test method is simple, exclusive and reproducible and it can be used as quality evaluation for AGO-ODT. © 2006 Editorial office of Foreign Medical Sciences.

Agomelatine as a Novel Pharmacotherapy of Anxiety Disorders / 대한정신약물학회지

Anxiety disorders are the most common mental health problems and frequently cause functional impairment. Although current pharmacological agents are recognized to be effective, partial or total resistance to drug treatment and distressing side effects have leaded to continued search of a new pharmacotherapy of anxiety disorders. Agomelatine is a novel agent with a melatonergic agonist at MT1 and MT2 receptors and an antagonist at 5HT2C receptors. Despite substantial evidence of its antidepressant properties, the anxiolytic properties of agomelatine have been underscored. Therefore, this article reviews previous studies on anxiolytic properties of agomelatine. In several rat models, agomelatine actively reduces anxiety-related behaviors comparable to benzodiazepine. These anxiolytic properties seem to be mediated by both melatonergic and 5HT2C receptors. Randomized, double-blind, clinical trials demonstrated that agomelatine 25-50 mg/day significantly reduced anxiety symptoms in patients with generalized anxiety disorder as well as major depressive disorder. Recently, cases of panic disorder and social anxiety disorder successfully treated with agomelatine were reported. In addition, the tolerability of agomelatine seems broadly favorable, particularly in sexual dysfunction and discontinuation syndrome. Based on these sound efficacy and tolerability profiles, further studies on the use of agomelatine in anxiety disorders will be required for wider clinical application.

Agomelatine: Antidepressant with a New Mechanism of Action / 대한정신약물학회지

Currently available pharmacotherapies for depression still have a limited antidepressant efficacy with a delayed onset of several weeks, and still cause side effects. These unmet needs represent important reasons to continue to search for novel treatment options. A disorganization of circadian rhythms has been suggested to play an important role in the pathophysiology of major depression. Agomelatine is a new agent with a unique pharmacological profile. Agomelatine is both an agonist of melatonergic MT(1) and MT(2) receptors and a serotonergic 5-HT(2C) receptor antagonist. Many clinical trials have demonstrated the superior efficacy of agomelatine in comparison with placebo in the treatment major depressive disorder at the standard dose of 25 mg/day, with the possibility of increasing doses to 50 mg/day in those patients with insufficient improvement. Agomelatine was even effective in severely depressed patients. The safety and tolerability of agomelatine was comparable to placebo. It does not induce the side effects including serotonin syndrome and sexual dysfunction or discontinuation syndrome typical to other therapies, such as selective serotonin reuptake inhibitors. These properties give agomelatine a definite clinical advantage in the treatment of depression.