Can Nocebo Effects Be Reduced via Open- and Closed-Label Counterconditioning?

backgroundThe overwhelming evidence of nocebo effects adversely affecting the experience of physical symptoms, such as pain, puts emphasis on the study of possible strategies to reduce nocebo effects. Counterconditioning, during which a previously conditioned effect is reversed, has been shown to be a possible promising strategy in a previous study in an open-label design, in which people were informed about the use of inert treatments and the counterconditioning procedure. However, it is unclear whether open-label counterconditioning is as effective as closed-label procedures in comparison to extinction.

methodsIn a randomised controlled trial, we investigated in 66 healthy female participants whether conditioned nocebo effects on pressure pain can be reduced via open-label counterconditioning, closed-label counterconditioning, or extinction.

resultsA significant reduction of nocebo effects was found after open-label counterconditioning (d = 1.13), closed-label counterconditioning (d = 0.69), and extinction (d = 0.66). Open-label counterconditioning was more effective than extinction (d = 0.85), reversed the nocebo effect, and also resulted in a placebo effect. Closed-label counterconditioning was more effective than extinction (d = 0.45) in the sensitivity analyses of nocebo responders only. Finally, larger placebo expectancies predicted a higher response to the open- and closed-label counterconditioning procedures, but not extinction.

conclusionsThese results show that particularly open-label counterconditioning is an effective method to modulate nocebo effects on pressure pain. This provides promise in designing non-deceptive learning-based treatments to reduce nocebo effects in diverse patient groups, including chronic pain disorders. SIGNIFICANCE STATEMENT: Few studies have investigated the efficacy open-label counterconditioning to reduce nocebo effects or have compared it to deceptive reduction strategies. The current study demonstrates that open-label counterconditioning is as effective as more deceptive nocebo-reducing strategies and may thus be a promising new method for reducing nocebo effects in a non-deceptive and ethical manner. Results can be helpful while designing learning-based treatments to reduce nocebo effects in patients with, for example, chronic pain disorders.

trial registrationClinicalTrials.gov identifier: NCT05284383.