Harnessing placebo effects and mitigating nocebo effects: implications for clinical practice in psychiatry and...

In psychiatry and medicine, there is a long history of framing placebo effects primarily as nuisance factors and focusing on how they should be minimised in clinical trials. However, a new view on placebo effects has emerged with advances in understanding their complex neurobiology and observations of unexpectedly large placebo responses in recent psychiatric trials. In particular, novel therapeutic device trials for depression have shown placebo-group remission rates nearing 50%. Instead of considering these studies as a failure and moving on, questions should be raised on how such responses are possible and how these effects can be harnessed for the benefit of patients. There have also been important new insights into the mechanisms of nocebo effects and analogous questions on how best to mitigate the effect of negative expectations on symptoms and medication side-effects. In this Review, paper 1 of 2 on reconceptualising placebo and nocebo effects, we discuss the rationale, strategies, and ethical considerations related to harnessing placebo effects and mitigating nocebo effects in clinical practice, including discussion of target patient populations, traditional pure and impure placebos, authorised deception, honest open-label placebo, pharmacotherapy dose reduction via conditioned placebo, nocebo education, nocebo reframing, and other ways to apply principles underlying placebo and nocebo effects, such as shifting mindsets and enhancing the therapeutic context. Lastly, we highlight the centrality of this topic to psychiatry, but explore how better understanding the interactions of mind, brain, and body-epitomised by placebo and nocebo effects-has crucial relevance across medicine.