Agomelatine as effective as other antidepressants, better tolerated

By Rob Goodier

NEW YORK (Reuters Health) - Agomelatine, a new melatonergic antidepressant, appears to be as effective as standard antidepressants and may be better tolerated, according to the researchers behind a new meta-analysis.

Still, agomelatine is pricey and should be considered a second-line treatment for patients who do not respond well to other drugs, said Dr. David Taylor, who led the work.

"Consider agomelatine in those intolerant to sedation, nausea, insomnia or sexual adverse effects caused by other antidepressants," Dr. Taylor, from King's College London, told Reuters Health by email. "The need for LFT (liver function tests) monitoring also restricts the use of agomelatine, although I do not believe it is inherently more hepatotoxic than any other antidepressant."

Agomelatine is sold as Valdoxan in Europe, but has not been approved in the U.S. Dr. Taylor has received personal fees and grants from Servier Laboratories, which developed the drug, though the new study did not have specific funding.

The researchers, whose findings were published online March 19 in BMJ, analyzed 20 trials with a total of 7,460 participants. Eleven trials had been published, four were from the European Medicines Agency and five from the manufacturer.

The team found that agomelatine performed significantly better than a placebo with an effect size of 0.24. And the drug was equally as effective as other antidepressants with a standardized mean difference of 0.00.

Overall, patients were no more likely to discontinue agomelatine than either placebo or active comparators. However, patients on agomelatine were significantly less likely to stop treatment due to adverse events than were those on other antidepressants (relative risk, 0.61).

The risk of bias was low, the researchers say, although published studies were more likely to find benefits than were unpublished ones.

In an editorial published with the study, Dr. Gilles Ambresin from the University of Lausanne, Switzerland, notes that while agomelatine may be as effective as other antidepressants, that effect is still only slightly better than placebo.

In general, he writes, antidepressants trump placebo only for patients with severe depression.

"I would encourage colleagues treating patients with depression not to forget to consider psychotherapy for mild or moderate depression and as a combined treatment for severe depression," Dr. Ambresin added in an email to Reuters Health. "Psychotherapy is recommended in current guidelines and is often patients' preferred first treatment."

Dr. Surendra Singh, a psychiatrist at the University of Wolverhampton in the UK who was not involved in the study, raised a number of concerns about its methods.

"The conclusion that agomelatine is significantly more effective than placebo should have been further qualified in statistical and/or clinical terms as statistically significant () results do not necessarily translate into clinical superiority based on generally perceived criteria (for effect size), including the one advocated by the Cochrane Group for anti-depressant medications," said Dr. Singh, who led an earlier meta-analysis on agomelatine that also found a small effect size.

In addition, Dr. Singh pointed out, a lack of difference in efficacy measurements does not imply equivalence, statistically speaking. "There are statistical methods to test equivalence of efficacy parameters and that should have been used to support this specific claim," Dr. Singh said.

SOURCE: http://bit.ly/1jVE5nk and http://bit.ly/1r8ELGQ

BMJ 2014.