The Melatonergic System in Mood and Anxiety Disorders and the Role of Agomelatine: Implications for Clinical Practice

Berardis, Domenico De; Marini, Stefano; Fornaro, Michele; Srinivasan, V.; Iasevoli, Felice; Tomasetti, Carmine; Valchera, Alessandro; Perna, Giampaolo; Quera-Salva, Maria-Antonia; Martinotti, Giovanni; Giannantonio, Massimo Di

doi:10.3390/ijms140612458

Cited by 70 publications

(47 citation statements)

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“…In addition to using behavioural animal models, a chronic stressor model 'Sucrose preference test' to test the antidepressant effect of drug treatments and combinations was also employed 8,23 . In this model, mice were exposed sequentially to a variety of stressors.…”

Section: Discussionmentioning

confidence: 99%

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Untitled

2018

IJPSR

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ABSTRACT:There is unmet need in the treatment of stress induced depression on suggesting requirement of new therapeutic agent. A combination therapy of antidepressants sertraline (5 mg/kg), duloxetine (10 mg/kg) and agomelatine (8 mg/kg) are used in different combinations of doses by intra-peritoneal route. Swiss albino mice were used as an animal model for stress-induced depression; mice were divided into eight groups. Depression was induced through forced swim test, tail suspension test and sucrose preference test (chronic mild stress model). Efficacy of combination therapy was analyzed in specific regions of mice brain associated with depression (hippocampus, cerebral cortices and the whole brain) through brain monoamine estimation by HPLC (Highperformance liquid chromatography) with fluorescence detector. Three drug combination [Agomelatine (2.67 mg/kg) plus duloxetine (3.33 mg/kg) plus sertraline (1.67 mg/kg)] showed antidepressant activity in invivo animal model testing parameters (decrease in immobility period, increase in swimming count and climbing count and increase sucrose consumption) than other treated group. In the same group, improvement in brain monoamine profile was observed illustrating antidepressant activity (increasing dopamine, serotonin and norepinephrine level in hippocampi, cerebral cortex and whole brain). These findings could be further probed with the aim of understanding the interaction between agomelatine plus duloxetine plus sertraline as a future endeavour.

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Section: Discussionmentioning

confidence: 99%

“…Sucrose Preference Test: Intake and preference for sucrose solutions are the exact measures of anhedonia commonly used and accepted in the CMS literature 8 . All mice were kept in individual cages and were subjected to chronic mild stress protocol.…”

Section: Tail Suspension Test (Tst)mentioning

confidence: 99%

Untitled

2018

IJPSR

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“…Agomelatine is one of the novel drugs in the antidepressant category with unique mechanism of action. It has MT 1 and MT 2 agonist and 5-HT 2c antagonist properties with pro-chronobiological effect [11]. It is an analogue of melatonin with high binding affinity to MT 1 and MT 2 G protein coupled melatonergic receptors [12].…”

Section: Discussionmentioning

confidence: 99%

A Comparative Study of Efficacy and Safety of Agomelatine and Escitalopram in Major Depressive Disorder

Komaram

Nukala

Palla

et al. 2015

JCDR

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Background: Major depressive disorder (MDD) is a mental disorder characterized by episodes of depressed mood, loss of interest or pleasure, feeling of guilt or low self-esteem, loss of energy, altered sleep patterns and difficulty in concentration.Objective: This study was carried out to compare the efficacy and safety of Agomelatine with Escitalopram in the treatment of major depressive disorder. design and Setting: This is a prospective study conducted at Outpatient Department of Psychiatry, GSL Medical College & General hospital, Rajahmundry, India. Materials and Methods:Patients with newly diagnosed major depressive disorder (DSM-IV-TR) with minimum score of 20 in Hamilton depression rating scale were randomly assigned Agomelatine (25-50 mg/day) or Escitalopram (10-20 mg/day) for a period of 8 weeks. The main efficacy outcome considered was the mean change of HAM-D17 score from baseline to end of therapy.Secondary outcome measures were Clinical Global Impressionsimprovement (CGI) and severity (CGI-S) rating scales.Statistical Analysis: Student t-test was used for comparing the groups and chi-square test was used for assessing the qualitative variables. For all statistical analysis p<0.05 was considered statistically significant. results:The drugs under study effectively reduced depressive symptoms at all the time points. The percentage of responders at 8weeks (last post baseline value) was 65.38% with Agomelatine and 57.40% with Escitalopram. The difference between the drugs was statistically not significant in all evaluations (p>0.05). The mean CGI-S and CGI-I scores were decreased in both the groups (p<0.05) and there was no statistically significant difference between the groups at any assessment during the study period. Both the treatment groups showed favourable safety profile. conclusion:The study results supported that Agomelatine is therapeutically similar to Escitalopram in terms of antidepressant effect.

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“…Therefore, melatonin readjusts this highly variable rhythm existing in these disorders. 13 The dose of melatonin demarcates the physiological and pharmacological effects of melatonin. Supraphysiological levels of melatonin are attained at "pharmacological" dose, while a "physiological" dose provides plasma levels of the same order of magnitude as that of a usual nocturnal peak.…”

Section: Melatonin -Pharmacological and Clinical Rolementioning

confidence: 99%