Placebo-controlled antidepressant drug trials. Considering the ethical implications

Abstract

For the approval of a new antidepressant for clinical use drug authorities still demand the proof of a significantly superior efficacy of the compound over placebo shown in controlled comparison studies. On the other side serious ethical concerns have been raised upon the use of placebos in clinical trials with depressed patients in that this would implicitly mean a withholding of an efficacious treatment from patients in the control groups of such trials. This article summarises frequently quoted arguments for and against placebo use in antidepressant clinical trials focussing on the specific issues involved in the therapeutic effect of antidepressants and placebos in depressed patients and discusses measures that might contribute to study designs that may better evaluate the true efficacy of a new drug while keeping the risk for the individual patient at the lowest possible level. A worldwide solution of the problem is clearly called for. A ban of placebos in antidepressant trials as it might be derived from the Declaration of Helsinki should be postponed until antidepressants with a more convincing superiority over placebo have been developed.