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.
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Article: Agomelatine in the treatment of major depressive disorder: potential for clinical effectiveness.
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ABSTRACT: Objective Antidepressants are at best 50–55% effective. Non-compliance and the antidepressant discontinuation syndrome (ADS) are causally related yet poorly appreciated. While ADS is associated with most antidepressants, agomelatine seems to be devoid of such risk. We review the neurobiology and clinical consequences of antidepressant non-compliance and the ADS. Agomelatine is presented as a counterpoint to learn more on how ADS risk is determined by pharmacokinetics and pharmacology.DesignThe relevant literature is reviewed through a MEDLINE search via PubMed, focusing on agomelatine and clinical and preclinical research on ADS.ResultsAltered serotonergic dysfunction appears central to ADS so that how an antidepressant targets serotonin will determine its relative risk for inducing ADS and thereby affect later treatment outcome. Low ADS risk with agomelatine versus other antidepressants can be ascribed to its unique pharmacokinetic characteristics as well as its distinctive actions on serotonin, including melatonergic, monoaminergic and glutamatergic-nitrergic systems.Conclusions This review raises awareness of the long-term negative aspects of non-compliance and inappropriate antidepressant discontinuation, and suggests possible approaches to “design-out” a risk for ADS. It reveals intuitive and rational ideas for antidepressant drug design, and provides new thoughts on antidepressant pharmacology, ADS risk and how these affect long-term outcome. Copyright © 2014 John Wiley & Sons, Ltd.Human Psychopharmacology Clinical and Experimental 11/2014; 29(6). DOI:10.1002/hup.2429 · 1.85 Impact Factor
Article: Agomelatine in breast milkThe International Journal of Neuropsychopharmacology 07/2012; 16(2):1-3. DOI:10.1017/S1461145712000648 · 5.26 Impact Factor
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ABSTRACT: There is still considerable controversy about the onset and time course of improvement with antidepressants in the treatment of major depressive disorder. Previous studies suggested a delayed-onset hypothesis with therapeutic improvement taking several weeks, but recent meta-analyses have shown support for earlier onset of improvement within the first week or two of treatment. This paper briefly reviews the evidence, focused on antidepressant studies published since 2006, for early onset of improvement within the first 2 weeks of treatment. A PubMed electronic search was conducted with selection of relevant studies from 2007 to March 2012. With the caveat of methodological limitations, results from randomized clinical trials, meta-analyses and naturalistic studies consistently show that: (1) antidepressants in general have early onset of improvement, (2) some antidepressants, including the novel mechanism agent, agomelatine, are associated with early improvement in both core and specific symptoms such as anhedonia and sleep–wake disturbances, and (3) early improvement predicts sustained response and remission. Use of newer statistical methods to examine individual response trajectories may address some of the methodological limitations of previous studies. The predictive value of early improvement has important clinical relevance for antidepressant treatment. Measurement-based assessment for response should occur earlier and more frequently. A lack of improvement (defined as ≤20% reduction from baseline in scores on a depression rating scale) at 2–3 weeks after initiation of an antidepressant should prompt the clinician to consider a change in management.European Neuropsychopharmacology 01/2012; 22:S492–S498. DOI:10.1016/j.euroneuro.2012.07.005 · 5.40 Impact Factor