Agomelatine in the treatment of major depressive disorder: potential for clinical effectiveness.
ABSTRACT To demonstrate the clinical effectiveness of an antidepressant drug requires evidence beyond short- and long-term efficacy, including a favourable adverse-effect profile and sustained treatment adherence. Under these conditions, patients should experience enhanced social and functional outcomes. The novel antidepressant agomelatine, a melatonergic MT(1)/MT(2) receptor agonist with serotonin 5-HT(2C) receptor antagonist activity, displays antidepressant efficacy with a favourable adverse-effect profile that is associated with good patient adherence. Specifically, agomelatine has demonstrated significant short-term (6-8 weeks) and sustained (6 months) antidepressant efficacy relative to placebo, as well as evidence of relapse prevention (up to 10 months). In head-to-head comparative studies with venlafaxine and sertraline, there was evidence of early (at 1-2 weeks) and sustained (at 6 months) advantages for agomelatine. In addition to evidence of early efficacy, agomelatine also restored disturbed sleep-wake patterns early in treatment. There was no evidence of antidepressant-induced sexual dysfunction, weight gain or discontinuation-emergent symptoms. Agomelatine has demonstrated a range of properties that suggest it could offer advantages over current treatments for major depressive disorder, although further comparative trials are still required, as is evidence from real-world clinical practice.
Full-textDOI: · Available from: Sidney H Kennedy, May 25, 2015
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Article: Agomelatine in the treatment of major depressive disorder: potential for clinical effectiveness.
SourceAvailable from: Domenico De BerardisMelatonin: Therapeutic value and Neuroprotection, 1 edited by Venkataramanujam Srinivasan, Gabriella Gobbi, Samuel D Shillcutt, Sibel Suzen, 10/2014: chapter 23: pages 289-308; CRC press., ISBN: 9781482220094
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ABSTRACT: Agomelatine (AGM) was approved for the treatment of major depressive disorder (MDD) in adults by the European Medicines Agency (EMA) in February 2009. It is an analogue of melatonin and features a unique pharmacodynamic profile with agonism on both types of melatonergic receptors (MT1/MT2) and antagonism at serotonergic 5-HT2C receptors. There is, however, an ongoing debate regarding the efficacy and safety of this novel antidepressant agent, originally evoked by claims of a significant publication bias underlying the assessment of AGM being an effective antidepressant. Indeed, two recent comprehensive metaanalyses of published and unpublished clinical trials found evidence for a relevant publication bias. However, due to its statistically significant advantage over placebo based on the results of these metaanalyses AGM must be referred to as an effective antidepressant agent in the acute phase of MDD. However, the effect sizes of AGM in the treatment of MDD were evaluated as being small in comparison to other antidepressant agents. In addition, there is insufficient evidence for the efficacy of AGM in relapse prevention of MDD. Apart from efficacy issues, AGM appears to have the potential to exhibit severe hepatotoxicity (the EMA has identified AGM-associated “hepatotoxic reactions” as a new safety concern in September 2013) that is currently poorly understood. Considering these aspects, it seems inappropriate to evaluate AGM as an antidepressant agent of first choice. Nevertheless, its unique mechanism of action with particular sleep modulating effects may represent a specific treatment strategy for patients with particular characteristics; further studies with thorough characterization of patients are needed to test this hypothesis.Journal of Applied Statistics 09/2014; 12(5). DOI:10.2174/1570159X12999140619122914 · 0.45 Impact Factor
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ABSTRACT: We report herein the racemic resolution and pharmacological evaluation of naphthalenic ligand analogues of compound 3a. Propionamide 3b and fluoroacetamide 3c showed a good pharmacological profile towards MT1, MT2 and 5-HT2C. Hence, their enantiomers were successfully separated from racemates (±)-3a and (±)-3b and evaluated for their binding affinities and antidepressant activity. Binding results revealed that (−)-R-enantiomers were more potent than (+)-S-enantiomers. Furthermore, the (−)-R-enantiomers exhibited high binding affinities with partial agonist activity at melatonin MT1 and MT2 receptor subtypes and antagonist activity at the serotonin 5-HT2C receptor subtype. The R-fluoroacetamide 3c demonstrated the most potent binding affinity towards the 5-HT2C receptor subtype (pKi = 6.73 ± 0.02).Medicinal Chemistry Communication 08/2014; 5(9). DOI:10.1039/C4MD00149D · 2.63 Impact Factor