Dataset Information

Agomelatine in the treatment of major depressive disorder: an assessment of benefits and risks.

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 Indeed, two recent comprehensive metaanalyses of published and unpublished clinical trials found evidence for a relevant publication bias.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.

SUBMITTER: Gahr M

PROVIDER: S-EPMC4243030 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Agomelatine in the treatment of major depressive disorder: an assessment of benefits and risks.

Gahr Maximilian M

Current neuropharmacology 20140901 5

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 publicat ...[more]

PMID: 25426008

Similar Datasets

Project description:Background: Major Depressive Disorder (MDD) is a moderately heritable disorder with a high lifetime prevalence. At present, laboratory blood tests to support MDD diagnosis are not available. Methods: We used a classifier approach on blood gene expression profiles of a unique set of non-medicated subjects (MDD patients and controls) to select genes of which expression is predictive for disease status. To reveal blood gene expression changes related to MDD disease, we applied a powerful ex vivo stimulus to the blood, i.e. incubation with lipopolysaccharide (LPS; 10 ng/ml blood). Results: Based on LPS-stimulated blood gene expression using whole-genome microarrays in 42 subjects (primary cohort; 21 MDD patients (mean age 42.3 years), 21 healthy controls (mean age 41.9 years)), we identified a set of genes (CAPRIN1, CLEC4A, KRT23, MLC1, PLSCR1, PROK2, ZBTB16) that serves as a molecular signature of MDD. These findings were validated for the primary cohort using an independent quantitative PCR method (P = 0.007). The difference between depressive patients and controls was confirmed (P = 0.019) in a replication cohort of 13 patients with MDD (mean age 42.8 years) and 14 controls (mean age 45.6 years). The MDD-signature score comprised of expression levels of 7 genes could discriminate depressive patients from controls with sensitivity of 76.9% and specificity of 71.8%. Conclusions: We show for the first time that molecular analysis of stimulated blood cells can be used as an endophenotype for MDD diagnosis, which is a milestone in establishing biomarkers for neuropsychiatric disorders with moderate heritability in general. Our results may provide a new entry point for following and predicting treatment outcome, as well as prediction of severity and recurrence of MDD. In total, 33 MDD patients and 34 healthy controls were analyzed using basal gene expression in whole blood, and gene expression from whole blood that was stimulated with LPS for 5-6 h, using microarrays. Patients were arbitrarily selected from all patients to serve as primary cohort (nMDD = 21 (MDD01-MDD21); nControls = 21 (Con01-Con21)), or replication cohort (nMDD = 12 (MDD22-MDD35); nControls = 13 (Con22-Con37)) using microarrays. This submission does not include Samples CON21_LPS or CON30_LPS.

Project description:BackgroundMajor depressive disorder (MDD) constitutes an important public health problem, as it is highly prevalent in the industrialized world and it is associated with substantial economic consequences for patients, health care providers, insurance and social security organizations and employers. To conduct an economic evaluation comparing agomelatine with other commonly used alternatives for treating patients with major depressive disorder (MDD) in Greece.MethodsAn existing international Markov model designed to evaluate the cost-effectiveness of agomelatine was adapted to the Greek setting. It reflects six different health states, in which patients may move on a monthly basis. The analysis was undertaken from a societal perspective. Transition probabilities, utilities and costs assigned to each health state were extracted from the published literature, government sources and expert opinion. Data reflects the year 2012 and was discounted using a rate of 3.5%. Probabilistic analysis was undertaken to deal with uncertainty.ResultsBase case analyses revealed that agomelatine is a dominant therapy for MDD relative to escitalopram, fluoxetine and sertraline, and it appeared to be cost-effective compared to venlafaxine (ICER: €547/QALY). Agomelatine remained a dominant treatment against generic sertraline and fluoxetine, and it appeared to be a cost-effective alternative compared to generic venlafaxine and escitalopram (ICER: €1,446/QALY and €3,303/QALY, respectively). Excluding the indirect cost from the analysis, agomelatine remained a cost-effective alternative over all comparators. In the probabilistic sensitivity analysis agomelatine was dominant in 44.5%, 89.6%, 70.6% and 84.6% of simulated samples against branded venlafaxine, escitalopram, fluoxetine and sertraline, respectively.ConclusionThe present evaluation indicates that agomelatine is either a dominant or a cost-effective alternative relative to branded or generic alternatives, in Greece.

Project description:Trazodone is a triazolopyridine derivative that belongs to the class of serotonin receptor antagonists and reuptake inhibitors (SARIs). The drug is approved and marketed in several countries worldwide for the treatment of major depressive disorder (MDD) in adult patients. In clinical studies, trazodone has demonstrated comparable antidepressant activity to other drug classes, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline (norepinephrine) reuptake inhibitors (SNRIs). Moreover, the SARI action of trazodone may overcome the tolerability issues that are often associated with second-generation antidepressants such as SSRIs (i.e. insomnia, anxiety and sexual dysfunction). Recent focus has been placed on the development of a new prolonged-release once-a-day formulation of trazodone (TzCOAD), which may provide improved tolerability over the conventional immediate-release formulation of trazodone. Clinical studies have led to the recent approval in the USA of TzCOAD (as Oleptro™; Angelini Labopharm LLC, Princeton, NJ, USA), which may see resurgence of interest in the drug for the management of patients with MDD. Although trazodone is approved for the treatment of depression, evidence supports the use of low-dose trazodone as an off-label hypnotic for the treatment of sleep disorders in patients with MDD. The most common adverse effects reported with trazodone are drowsiness (somnolence/sedation), headache, dizziness and dry mouth. Other events reported, albeit with low incidence, include orthostatic hypotension (particularly in elderly patients or those with heart disease), minimal anticholinergic activity, corrected QT interval prolongation and torsade de pointes, cardiac arrhythmias, and rare occurrences of priapism and suicidal ideation. Overall, trazodone is an effective and well tolerated antidepressant (SARI) with an important role in the current treatment of MDD both as monotherapy and as part of a combination strategy. Trazodone is effective in controlling a wide range of symptoms of depression, while avoiding the negative effects on sleep seen with SSRI antidepressants. The recently approved prolonged-release formulation should provide further optimization of this antidepressant and may be useful for enabling an appropriate therapeutic dose to be administered with improved patient compliance.

Dataset Information

Agomelatine in the treatment of major depressive disorder: an assessment of benefits and risks.

Publications

Agomelatine in the treatment of major depressive disorder: an assessment of benefits and risks.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets