Publication bias and outcome reporting bias: agomelatine as a case example.

Publication bias and outcome reporting bias contribute to distorted perceptions of drug efficacy and the underreporting of adverse events. To demonstrate these biases, this article describes how the clinical profile of the antidepressant agent agomelatine (Valdoxan(®)) has been presented in the literature. Agomelatine has been systematically assessed in 10 short-term placebo-controlled studies and three long-term placebo-controlled relapse prevention studies. Five published trials demonstrated clinically modest but statistically significant benefits over placebo. Five unpublished trials did not find agomelatine more effective than placebo, but in two of these studies the active comparison drug (fluoxetine [Prozac(®)] or paroxetine [Paxil(®)]) was more effective than placebo. Agomelatine was more effective than placebo in one of three relapse prevention studies, but only the positive study was published. Based on what is evident in the entire published and unpublished dataset, agomelatine does not have a tremendously superior sleep and sexual effects profile. The risk of liver toxicity is also not prominently highlighted in the published literature.