A critique of recent studies on placebo effects of antidepressants: importance of research on active placebos

Abstract.

Objective: This review examines the recent literature on placebo effects in antidepressant drug research. Recent meta-analyses have suggested that antidepressants produce relatively small effects compared to placebo treatments, and that the effect sizes for placebo treatments are highly correlated with effect sizes for drug treatments across different studies. In addition, it is argued that "active placebos", i.e., drugs that are not antidepressants but do have discernible subjective or physiological effects, can also produce substantial changes on measures of depression. Thus, some researchers have called into question the "blind" nature of research using inert placebos, and also have questioned the efficacy of antidepressant drugs. Results: The studies reviewed indicate that it is premature to suggest that antidepressant drugs have little efficacy beyond their role as active placebos. In fact, there are several important methodological, conceptual and scholarly problems with some of the work that emphasizes the role of placebo effects in mediating the actions of antidepressant drugs. Conclusions: Many of the drugs listed as "active placebos" actually have some efficacy for the treatment of depression or related disorders, and several of these drugs are used clinically to augment the effects of antidepressants. It would be important for researchers to identify new active placebos as research tools in this area, and to focus on discriminating between placebo effects and the true therapeutic actions of antidepressant drugs. A new generation of well controlled experiments in this area could shed light on these important issues, and may lead to improved methods for the determination of antidepressant efficacy.