Ethical issues of placebo-controlled studies in depression and a randomized withdrawal trial in Japan: case study in the ethics of mental health research.

The use of placebo controls in psychiatric research is controversial. In this article, we focus on a troubling Japanese case of a randomized withdrawal trial of the antidepressant sertraline and analyze the ethical issues underlying it. First, we consider whether a placebo-controlled withdrawal trial should, in general, be considered more ethical than a standard placebo-controlled trial. We argue that the use of a placebo arm in this trial is ethically permissible but that there is no good reason to use a withdrawal trial design. Second, we discuss whether our moral evaluation of the use of placebo in this case should change when the special Japanese regulatory environment is taken into account. We argue that it should not and conclude that the use of withdrawal design in this case is ethically unacceptable.