Placebo-controlled trials in schizophrenia: Are they ethical? Are they necessary?

The current controversy as to the proper role of the placebo control in the evaluation of new treatments for schizophrenia requires an analysis that is sensitive to both ethical and scientific issues. Clinical equipoise, widely regarded as the moral foundation of the randomized controlled trial (RCT), requires the use of best available treatment as the control in RCT. Scientific criticisms of the use of an active control are examined and none present an insuperable barrier to the use of an active control. Indeed, scrutiny of the most recent argument for the use of placebo controls, 'assay sensitivity', suggests that the use of placebo may be the cause of the problem pointed to. Scientific, regulatory, ethical and legal advantages of the use of an active control are described. While the use of a placebo control may be acceptable in carefully defined circumstances, in most cases the use of an active control in schizophrenia research is ethically and scientifically preferable. (C) 1999 Elsevier Science B.V. All rights reserved.