Minimizing Drug Adverse Events by Informing About the Nocebo Effect—An Experimental Study

Abstract

Relevance: Informing patients about potential adverse events as part of the informed consent may facilitate the development of nocebo-driven drug adverse events (nocebo side effects). Objective: To investigate whether informing about the nocebo effect using a short information sheet can reduce nocebo side effects. Methods: A total of N = 44 participants with weekly headaches for at least 6 months were recruited using the cover story of a clinical trial for a headache medicine. In reality, all participants took a placebo pill and were randomized to the nocebo information group or the standard leaflet group. Participants were instructed to read the bogus medication leaflet entailing side effects information shortly before pill intake. The nocebo group additionally received an explanation about the nocebo effect as part of the leaflet. Questionnaires were completed at baseline, 2 min, and 4 days after the pill intake. We conducted general linear models with bootstrap sampling. Baseline symptoms were included as a covariate. Results: Most participants (70.5%) reported nocebo side effects at 2 min. Participants who received the nocebo information ( n = 24) reported less nocebo symptoms than the control group ( n = 20) (estimated difference: 3.3, BCa 95% CI [1.14; 5.15], p = 0.01, Cohen’s d = 0.59). Baseline symptoms, perceived sensitivity to medicine, and side effect expectations each moderated the group effect (estimated difference in slope: 0.47, BCa 95% CI [0.19; 0.73], p = 0.001, d = 0.75; 1.07 [0.27; 1.61], p = 0.006, d = 0.73; 1.57 [0.38; 2.76], p = 0.02, d = 0.58). No group differences were found at 4-day follow-up. After revealing the actual aim of the study, 86% of the participants evaluated the nocebo information to be helpful in general. Conclusions: Results provide the first evidence that informing about the nocebo effect can reduce nocebo side effects.

Informing About the Nocebo Effect Affects Patients’ Need for Information About Antidepressants—An Experimental Online Study

“…To handle this ethical dilemma, promising approaches targeted to reduce expectation-induced side effects while still respecting patient autonomy and truthfulness have been suggested. Experimentally validated strategies include framing side effect information positively ( 4 , 27 ), personalizing informed consent and educating about the medication’s mechanism of action ( 28 ), and explicitly informing about the nocebo effect itself ( 29 ). An important theoretical proposal suggests to contextualize the informed consent by providing medication information in a manner that is personalized to the patient’s characteristics, underlying disease, health status, and informational needs ( 30 ).…”

“…Being a theoretically discussed approach among experts, the patient’s view regarding this so-called authorized concealment remains unknown. Relevantly, very few individuals are aware of the nocebo effect and thus might not be able to express the need for respective medication information ( 29 ).…”

European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB): An Update on the Pediatric CEUS Registry on Behalf of the “EFSUMB Pediatric CEUS Registry Working Group”

“…In a 16-year-old girl 1/1657 (0.06 %) (Patient 14), a hyperventilation attack reported prior to injection was considered a nocebo side effect [44,45]. In three patients (Patients 4, 5 and 6), mild symptoms occurred 4-8 hours after the examination procedure but were unlikely attributable to the UCA since it is eliminated within minutes from the body.…”

Preventing Adverse Events of Chemotherapy for Gastrointestinal Cancer by Educating Patients about the Nocebo Effect: A Randomized-controlled Trial

“…Arguably, these AEs are the result of patients' negative expectations, evoked for example during informed consent (IC) (11). The physiological effects of expectations have been underpinned by neurobiological correlates, primarily in nocebo pain modulation (12,13).…”