Placebos and paradoxes in psychiatric research: an ethics perspective.

The use of placebos in clinical trials, particularly in research with mentally ill people, has emerged as a subject of considerable controversy. We first outline ethical aspects of the primary scientific arguments for and against placebo use in research. Three examples of paradoxical aspects of the ethical use of placebos are discussed: involvement of relatively more vulnerable populations, use of apparently "less than standard" therapy, and the omission of information in placebo comparisons. In the current scientific and regulatory context, placebo use in psychiatric research may be necessary for scientific reasons, and when certain conditions are present, it may be justified on ethical grounds. Four key recommendations to facilitate the ethical use of placebos in research trials are presented. We conclude that placebo trials should be undertaken only after careful evaluation of alternative scientific strategies and, as with all human research, with great respect and genuine consideration for the individuals who choose to participate in these protocols.