Why do open-label placebos work? A randomized controlled trial of an open-label placebo induction with and without extended information about the placebo effect in allergic rhinitis

Abstract

Background: Several studies demonstrated that placebo treatment may have a significant impact on many different symptoms. While in the traditional view concealment of the placebo is essential, recent studies report intriguing evidence that placebos may work even without deception. For example, it has been demonstrated that open-label placebos can improve symptoms in allergic rhinitis. However, the mechanisms of how placebos without concealment work remain unknown.

Trial design: In order to examine expectancy effects we conducted a randomized controlled trial (N = 46), in which patients with allergic symptoms received either placebos without deception or no pills at all. In half of those patients we induced positive expectations about the placebo effect. After two weeks we tested whether symptoms and quality of life had changed.

Results: Results revealed that open-label placebos improved allergic symptoms more than the control group. Inducing positive expectations had no effects on the improvement of allergic symptoms (the primary and more objective outcome), but on mental sum scores of the quality of life questionnaire.

Conclusions: Placebos without deception can improve symptoms in allergic rhinitis. Positive expectations do not contribute to the efficacy of open-label placebos, but seem to have an effect on more global and subjective well-being (mental or emotional quality of life).

Clinical trial registration number: German Clinical Trials Register, DRKS00012303.

Fig 1. Flow diagram of patient’s enrollment.

Fig 2. Changes of allergic symptoms for open-label placebo and control group (mean and standard error).

Patients indicated their response on a seven-point scale ranging from ‘never’ (1) to ‘always’ (7) (composite score of all symptoms). Results demonstrate significantly stronger improvement for the open-label placebo group relative to the control group. * p = 0.02.

Fig 3. Data of the allergic diary demonstrate improvement of the open-label placebo group over time.

Fig 4. Changes of allergic symptoms for open-label placebo and control group for single symptom groups (mean and standard error).

Results show significant improvements for the open-label placebo group but not for the control group. * p < 0.05, (*) p = 0.06.

Fig 5. Change of mental or emotional quality of life (mental sum score of the SF-36) when receiving detailed information on placebos (raising positive expectancies) compared with no detailed information about the power of placebos.

Results revealed stronger improvement of mental or emotional quality of life when being told that placebos are powerful (irrespective of receiving open-label placebos).