Placebo–controlled trials in major depression are necessary and ethically justifiable

Abstract

Despite numerous placebo–controlled clinical trials with antidepressants were conducted in humans and a large amount of data was already published in the last two decades, the members of the 4^th European Expert Forum on Ethical Evaluation of Placebo–Controlled Studies in Depression were agreed that placebocontrolled trials with antidepressants also in the future are essential. Placebo–controlled studies measure the effect size in a reliable way and establish sensitivity and internal validity. They are scientifically sound and interpretable in terms of efficacy and are, therefore, clinically more relevant than non–placebo–controlled clinical trials. The “Note of Clarification” of the Declaration of Helsinki opens up where such trials are acceptable.

This statement of the members of the 4^th European Expert Forum is directed to academia, members of Ethic Committees, regulators, and industry to facilitate their decisions towards clinical studies with antidepressants. ”Checklists” for the contents of patients information are given as well as for the investigator.

Placebo–controlled clinical trials are scientifically necessary, ethical and feasible. The administration of the placebo is in itself a non–specific treatment and experts agree that there appears to be no increased suicidal risk in the placebo–group of carefully selected and monitored study patients.