Brain Trust: The Placebo Effect as a Clinical Tool, A Discussion With Walter A. Brown, MD

BRAIN TRUST: CONVERSATIONS IN PSYCHOPHARMACOLOGY
Series Editor Joseph F. Goldberg, MD

Joseph F. Goldberg, MD, in this installment of "Brain Trust: Conversations in Psychopharmacology," sat down with Walter Brown, MD, to discuss the placebo effect in clinical psychopharmacology, including its mechanisms, the nocebo effect, ethical considerations, and practical strategies for harnessing placebo responses in everyday psychiatric practice.

Brown traced his interest in the placebo effect to his involvement in early SSRI clinical trials in the 1980s, in which approximately 58–60% of patients responded to active drug versus 40–45% to placebo—a gap he found surprisingly narrow.¹ He spent the next 30 years reviewing the literature and studying placebo responders, synthesizing his findings in a 2013 book, The Placebo Effect in Clinical Practice.

Brown identified expectation as the most widely studied mechanistic driver of the placebo effect. He also cited a 3-arm study of St John's wort, sertraline, and placebo in approximately 100 patients, in which outcome correlated more strongly with what patients believed they had received than with what they actually received—proposing that "the belief in what treatment you're getting has a more powerful effect than its actual pharmacologic activities."²

Brown and Goldberg also discussed the nocebo effect, noting that informing patients about potential side effects increased their likelihood of experiencing them, which was illustrated by some COVID-19 vaccine trials. Mitigation strategies included positive framing (highlighting the 90% who do not experience a side effect rather than the 10% who do) and "authorized concealment," in which patients consent to receiving only selected side effect information.

Brown urged clinicians to regard the placebo response "not a nuisance, which is what has been thought of for a long time, but as an important part of all healing, and it should be enhanced"—noting it accounted for roughly a third of treatment benefit. Goldberg agreed that maximizing placebo effects through optimistic framing, therapeutic alliance, and mobilization of hope can be an element of expert psychopharmacologic practice.

Dr Goldberg is a clinical professor of psychiatry at The Icahn School of Medicine at Mount Sinai in New York, NY and the immediate-past president of the American Society of Clinical Psychopharmacology.

Dr Brown is clinical professor emeritus of psychiatry and human behavior at Brown University.

References

1. Moncrieff J, Wessely S, Hardy R. Active placebos versus antidepressants for depression. Cochrane Database Syst Rev. 2004;2004(1):CD003012.

2. Sarris J, Fava M, Schweitzer I, et al. St John's wort (Hypericum perforatum) versus sertraline and placebo in major depressive disorder: continuation data from a 26-week RCT. Pharmacopsychiatry. 2012;45(7):275-8