Side effects following administration of open-placebos: A randomized controlled trial

Objective: To assess whether individuals reported more side effects and decreased mood after receiving an open-label placebo compared to a control group that received no treatment.

Methods: We randomized participants to receive an open placebo or no treatment. The primary outcome was reported side effects on the Side effect Attribution Scale (SEAS) at 15 min and at 24-h. We also examined negative mood as a secondary outcome and whether psychological variables influenced symptom reporting.

Results: At both 15 min and 24-h, participants who took the open-placebo reported a significantly higher number of symptoms (M = 2.03, SE = 0.42) than the control group (M = 1.14, SE = 0.20). Across both time points, participants who took the placebo also reported significantly greater negative mood (M = 6.28, SE = 0.27) than the control group (M = 5.59, SE = 0.16). There was no significant group by time interaction for symptoms or mood (ps > 0.32). Symptom reporting after taking the placebo was not correlated with baseline anxiety, perceived sensitivity to medicines, or modern health worries at either 15 min or 24-h (ps > 0.11).

Conclusions: The act of taking a treatment, even knowing it is a placebo, resulted in an increase in symptoms and negative mood reported immediately following pill-taking and 24 h later. These findings have implications for the use of open-label placebos and the prescription of medicines in general, as they suggest the process of taking a medicine may result in increased symptoms and an increase in negative mood.

Trial registration: The trial was preregistered at the Australian New Zealand Clinical Trials Registry (12622001570774).