Open-label placebo vs double-blind placebo for irritable bowel syndrome: a randomized clinical trial
Anthony Lembo, John M. Kelley, Judy Nee, Sarah Ballou, Johanna Iturrino, Vivian Cheng, Vikram Rangan, Jesse Katon, William Hirsch, Irving Kirsch, Kathryn T. Hall, Roger B. Davis, Ted J. Kaptchuk
Abstract
ABSTRACT: It is commonly believed that blinding to treatment assignment is necessary for placebos to have an effect. However, placebos administered without concealment (ie, open-label placebos [OLPs]) have recently been shown to be effective in some conditions. This study had 2 objectives: first, to determine whether OLP treatment is superior to no-pill control (NPC) in irritable bowel syndrome (IBS) and, second, to compare the efficacy of OLP against double-blind placebo (DBP). In a 6-week, 3-arm, randomized clinical trial, participants were randomized in equal proportions to 3 arms: OLP, DBP, or NPC. Two hundred sixty-two adults (72.9% women), with a mean age of 42.0 (SD = 18.1) years, participated in the primary study. The mean improvement on the IBS Severity Scoring System from baseline to the 6-week end point was significantly greater in OLP compared with that in NPC (90.6 vs 52.3, P = 0.038). Open-label placebo and DBP did not differ significantly on IBS Severity Scoring System improvement (100.3 vs 90.6, P = 0.485). Standardized effect sizes were moderate for OLP vs NPC (d = 0.43) and small for OLP vs DBP (d = 0.10). Participants treated with OLP reported clinically meaningful improvements in IBS symptoms that were significantly greater than those on NPC. Open-label placebo and DBP had similar effects that did not differ significantly, suggesting that blinding may not be necessary for placebos to be effective and that OLP could play a role in the management of patients with refractory IBS.