Agomelatine, is an agonist at melatonergic M1 and M2 receptors, and an antagonist at the 5-HT2c receptors. It does not increase the amine levels in the plasma, hence less likely to cause nausea, agitation, palpitations and dry mouth, which are associated with SSRI and SNRI. Lack of discontinuation symptoms following the abrupt withdrawal as well as fewer sexual side effects are considered as advantages of this medication.Though it is shown to be effective against placebo, clinicians would want to know its relative efficacy against other antidepressants.
Kasper and colleagues presents the pooled analysis from head- to head studies of agomelatine vs other antidepressants. Six studies were identified. They were all multi- centre (secondary care), randomized, double-blind, parallel-group studies in depressed outpatients in which the primary efficacy analysis was against venlafaxine, sertraline, fluoxetine and escitalopram ,paroxetine. Two studies are not yet fully published.
The pooled analysis included a total of 2034 outpatients .There were significant between- group differences in the rates of response on the HAM-D17 scale (P = 0.012) and the CGI-I scale (P = 0.032) .Fewer patients withdrew because of adverse events with agomelatine (6.9%) than with SSRI/SNRI (10.7%) (P < 0.001.) .
An increase of more than three times the upper limit of normal for alanine aminotransferase and/or aspartate aminotransferase was observed in 16 agomelatine-treated patients as against five in SSRI/SNRI-treated patients.
Comments: The advantage of agomelatine versus comparators is 5% in responder rates in this pooled analysis. The confidence interval of this difference of 5% between groups is very wide (1.11–9.05). SSRI/SNRI doses in the comparator studies are moderate only , for example sertraline (50-100), venlafaxine (75-100). Of the 6 included studies only one had HAMD17 score as primary outcome measure.In all others, sleep parameters were the primary outcome measure and HAMD 17 was secondary measure only.
Prescribers were recently asked to monitor LFT closely following fatal liver damage.(See previous blog on this). https://psychiatristupdate.wordpress.com/2012/10/19/risk-update-extra-caution-with-agomelatine/
This study was supported by Servier labs, who markets this medication.
Summary of the article:
Kasper S, Corruble E, Hale A, Lemoine P, Montgomery SA, Quera-Salva MA. Int Clin Psychopharmacol. 2012 :Sep. [Epub ahead of print]