Objective: One potential for bias in the evaluation of a new drug is the dose used, both for the new compound and for the reference drug. The present study compared fluoxetine dose and outcome in trials in which fluoxetine was the experimental drug with trials in which it was the comparator.
Methods: Systematic review of randomised controlled trials comparing fluoxetine with any other antidepressant in depressive patients. Studies were allocated to one of the following two groups: group 1 = fluoxetine was the experimental drug; group 2 = fluoxetine was the control drug. Trials were located by searching the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Controlled Trials Register.
Results: The systematic search yielded 103 randomised trials. Studies in which fluoxetine was the experimental drug adopted a higher dose regimen than group-2 studies. In the efficacy analysis, the weighted rate of fluoxetine responders was 70.1% (confidence interval 67.4%, 72.8%) in group-1 studies and 57.9% (57.2%, 58.7%) in group-2 studies. In the effectiveness analysis, the weighted rate of fluoxetine responders was 56.4% (55.3%, 57.6%) in group-1 studies and 51.9% (51.2%, 52.7%) in group-2 studies. The weighted rate of fluoxetine dropouts was higher in group-1 studies.
Conclusion: . Fluoxetine dose and outcome changed according to whether this drug was used as a new compound or as a reference.