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

Abstract

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).