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Antidepressant efficacy of agomelatine: meta-analysis of published and unpublished studies

BMJ 2014; 348 doi: https://doi.org/10.1136/bmj.g1888 (Published 19 March 2014) Cite this as: BMJ 2014;348:g1888

The meta-analysis of published and unpublished studies of agomelatine is misleading

Dear Editor,

I read with great interest the article entitled: “Antidepressant efficacy of agomelatine: meta-analysis of published and unpublished studies” soon after this paper was published by the BMJ. Because I’m aware of the phenomenon of unpublished and misreported human research involving active pharmacological principles, I also downloaded data (March 28, 2014) of agomelatine study registries from ClinicalTrials.gov and WHO ICTRP. In this first letter, I prefer to put emphasis on real data of published and unpublished agomelatine studies, allowing numbers to speak for themselves.

1. 12 out of 20 studies included in the study by Taylor and colleagues are unregistered. This data represents evidence that calculations of unpublished and published studies in clinical trial registries could be an understimate because an unknown number of unpublished and unregistered studies.

2. There is also evidence of other agomelatine studies, not included in this meta-analysis, and absent from clinical trial registries.

3. Over 80% of agomelatine studies are unpublished.

4. Quote from the article published by Taylor and colleagues follows.

"A meta-analysis of published trials suggested robust efficacy in major depression, with an estimated effect size of 0.26 compared with placebo.3”

- Quote from the abstract in the cited reference (3) is shown below this line.

"Agomelatine (n=1274) stood superior to placebo (n=689) by a small margin (SMD -0.26, p=3.48×10-11) and the superiority of agomelatine (n=834, dose ≥ 25 mg/d) over antidepressants (paroxetine, fluoxetine, sertraline, venlafaxine; n=864) was even smaller (SMD -0.11, p=0.02). Although there is evidence of the superiority of agomelatine over placebo and selected antidepressants, it is questionable whether the magnitude of effect size is clinically significant and sample characteristics are relevant to the general patient population with major depressive disorder."

5. Recent marketing campaigns of Valdoxan (agomelatine) in Colombia involve giving free samples of agomelatine. It’s concerning the misleading advertising of Valdoxan as it can be seen in the following video presented during the launch to the market of Valdoxan in Central America.

6. Raw data is available

7. List of published and unpublished agomelatine study records
http://dx.doi.org/10.6084/m9.figshare.1133646

8. Attrition in agomelatine clinical trials is considerably high. Patient flow is available in some agomelatine studies evaluated by the EMA.
URL: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Public_asses...

Competing interests: - I endorse the principles of open data in human biomedical research

09 August 2014
Jorge H Ramirez
Professor of Pharmacology
Universidad del Valle
Cl 4B 36-00 San Fernando. Section of Pharmacology, Department of Physiological Sciences, Faculty of Health. Cali, Colombia