Review Elmer Press J Clin Med Res • 2009;1(3):132-136 Ethical and Scientific Perspectives of Placebo-controlled Trials in Schizophrenia Yuval Melameda, b, Adiel Dorona, Orit Stein-Reisnera, Avi Bleicha Abstract Clinical trials for development of new medications are essen- tial in all fields of medicine. The requirement for a placebo arm in pharmaceutical trials presents ethical and clinical dilemmas that are especially complicated with regard to mentally ill persons whose free choice and ability to provide informed consent may be ques- tionable. On the other hand, we do not believe that this predica- ment justifies unconditional rejection of placebo use in psychiatry, when the investigational drug may ultimately provide substantial benefit for some patients. At the same time it is the psychiatrist’s responsibility to insure that investigators are adequately trained to conduct clinical trials and that stringent regulatory committees su- pervise the scientific, clinical and ethical aspects of the trials. Keywords: Placebo-control; Schizophrenia; Medical ethics; Clini- cal trials Introduction Clinical trials involving human subjects give rise to eth- ical and medico-legal dilemmas. Essential research of new drugs may potentially expose patients to ineffective medica- tions or to placebo. The complexity of the issue increases when dealing with mentally ill patients for whom there is no Manuscript accepted for publication June 30, 2009 aLev-Hasharon Mental Health Center, Netanya, Israel, affiliated to the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel bCorresponding author: Deputy Director, Lev Hasharon Mental Health Center. P.O.Box 90000, Netanya 42100, Israel. E-mail: ymelamed@post. tau.ac.il doi:10.4021/jocmr2009.07.1247 known cure, and whose ability to provide informed consent to participate in clinical trials may be questionable. In the absence of a consensus regarding criteria for placebo use Kotler and Witztum [1] claim that we are wit- nessing a growing controversy. This debate has practical im- plications for Ethics Committees (Internal Review Boards) when deliberating approval of participation in extensive es- sential psychopharmacological research. The issue has been addressed by psychiatrists in various countries [2]. We pres- ent the ethical considerations to be dealt with by the treating physicians and investigators. Declaration of Helsinki The basic principle of the Declaration is that each and every patient is entitled to the best treatment available [3]. In 1996 it was determined that in all medical research, every patient, including those in control groups is entitled to the best available treatment, and that placebo may be used only in the event that there is no proven treatment available. In the year 2000 a correction was added, which de- termined that the benefits, risks and effectiveness of new treatments must be weighed in comparison to the very best available treatment, and the use of a placebo arm should be limited to situations where there is no proven effective treat- ment. In 2002 the World Medical Association (WMA) insert- ed a clarification that claimed that placebo-controlled trials could be ethical, even where proven treatments are available in the event that: there are scientific/methodological grounds for inclusion of placebo in the trial as an essential condition to prove efficacy of the drug [4]. Research versus treatment Medical treatment and medical research differ. The Physician’s Oath, adopted by the General Assembly of the World Medical Association, (1948, amended 1968) pledges that “The health of my patient will be my first consideration”. Naturalistic or case control study designs do not interfere with the patients’ treatment regimens, and they are in accord with these principles of treatment. However investigations 132 Articles © The authors, Journal compilation © J Clin Med Res and Elmer Press™, www.jocmr.org