The researchers acknowledge that as with many meta-analyses, theirs has several limitations:
• only short term efficacy studies of agomelatine were considered, some of which did not have changes in depression rating scores as their primary outcome.
• The risk of bias assessment was hindered by poor reporting, thereby making it difficult to judge the quality of studies for some particular domains.
• Data were aggregated for 25 mg and 50 mg doses of agomelatine, which could result in some heterogeneity in effect size estimation, though agomelatine has not shown a clear dose response relation between these doses.
• There was a high level of heterogeneity observed for both placebo-controlled and comparator-controlled studies.
However they add that they were reasonably confident that all available data were captured, taking into account the information supplied by the European Medicines Agency and by the manufacturer and the appearance of the funnel plots.
They note that agomelatine is considered unsuitable as a first line treatment because it is a branded drug still protected by patent and therefore considerably more expensive than any of the large number of generic alternatives. Its use is further inhibited by the formal requirement for liver function testing. In addition, its long term benefit of remains unproved. They suggest however, that agomelatine is a drug worthy of consideration because of its better tolerability, and could be considered one of several sensible treatment options for those patients who cannot take standard antidepressants.
Agomelatine is a melatonergic agonist and 5-HT2C antagonist licensed for the treatment of major depressive episodes in adults. The NICE clinical guideline on depression recommends an SSRI in a generic form when an antidepressant is to be prescribed. It did not address agomelatine because the drug was not licensed at the time of data analysis. In 2011, NICE was unable to recommend its use in the NHS because no evidence submission was received from the manufacturer or sponsor of the technology.
Nb: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors, and the principal author has received personal fees and grants from Servier outside the submitted work.