Placebo and nocebo effects in depression: Implications for treatment and clinical trial designs

This chapter reviews evidence for placebo and nocebo effects in depression, including their mechanisms of action. The authors then consider how these effects could be used clinically. Meta-analyses indicate that antidepressants provide only marginal benefits over placebos, which suggests that placebos could benefit patients nearly as much as antidepressants do, but without medication side effects. Open-label placebos are a promising avenue for evoking these effects. It is also presented evidence for expectancy as an important mechanism underlying placebo and nocebo effects. It is discussed how expectancies regarding treatment efficacy and side effects could be manipulated to reduce side effects and improve clinical outcomes. In particular, the authors discuss how communication strategies such as contextualizing informed consent and framing treatment information can optimize treatment expectations, improve clinical outcomes, and reduce nocebo-related side effects. Finally, implications that such expectancy manipulations might have for clinical trial design are covered.