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Background Evidence for the nocebo effect, a phenomenon characterised by suboptimal treatment efficacy, worsening of symptoms, or the occurrence of adverse events caused by an individual’s negative treatment expectations, is growing across a multitude of medical fields. However, little attention has been paid to patients’ negative expectations and the nocebo effect within dentistry. Aim This review summarises essential evidence of the nocebo phenomenon especially in relation to pain and drug administration. Subsequently, an overview of the current evidence of the nocebo phenomenon in the dental field is presented. Methods A PubMed search was performed using keywords related to “nocebo,” “placebo,” “expectations,” and “dentistry.” In addition to the articles selected from the search, placebo/nocebo researchers and dental researchers added important references from their respective fields. Results Although research on the nocebo effect in dentistry is limited, available current evidence suggests that the factors, which is related to the nocebo effect are likely to play a role in dental practice. Conclusion Preliminary evidence from the review warrants further investigation into the nocebo effect in dentistry. Finally, based on the general knowledge of the nocebo effect, the review indicates fruitful arrays of research into the nocebo effect in dentistry.

A growing body of evidence suggests that the informed consent process, in which patients are warned about potential side effects of a treatment, can trigger a nocebo effect where expectations about side effects increase side effect occurrence. This has sparked an ethical debate about how much information patients ought to receive before a treatment while trying to balance the moral principles of patient autonomy and nonmaleficence. In keeping with the principle of patient autonomy, the opinion of patients themselves in relation to how much information they want about side effects is of utmost relevance in this debate. The literature was searched to identify surveys assessing patient attitudes towards side effect information. Across a broad variety of patient populations, treatment types, and countries, the majority of patients wished to be fully informed of potential side effects, particularly in relation to frequent and severe side effects, while only a small minority wanted minimal or no information at all. Results from this review suggest that nocebo research should focus on methods of avoiding nocebo effects of informed consent while ensuring that patients are well-informed about potential side effects.

Background:The nocebo response refers to the phenomenon where non-specific factors, including negative verbal suggestion and treatment expectations, cause adverse events (AE) following a placebo treatment. Non-specific factors are also likely to influence AE occurrence following administration of active pharmacological treatments.Objective: This meta-analysis aimed to estimate the nocebo response in dentistry by assessing the AEs prevalence in placebo-and active arms of randomised controlled trials (RCTs) assessing analgesic treatment following third molar (M3) surgery.Methods: A systematic search was performed in PubMed, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials. Eligible studies had to report the number of patients experiencing at least one drug-related AE (patients with AE ≥ 1) separately for the active and placebo arms. The proportion of patients with AE ≥ 1 and drug-related dropouts were pooled, and risk differences (RDs) between patients in the placebo-and active arm were calculated. Results:In 50 independent RCTs of 47 identified articles, the pooled rates of patients with AE ≥ 1 were 22.8% in the placebo arm and 20.6% in the active arm. The pooled rates of drug-related dropout were 0.24% in the placebo arm and 0.08% in the active arm. There were no significant RDs in patients with AE ≥ 1 and drug-related dropouts. Conclusion:These results show that patients in the placebo arm reported AEs to the same extent as patients receiving active treatment, suggesting that most AEs in analgesic medication following M3 surgery may be attributed to the nocebo phenomenon.

Objectives Previous studies have found little association between objective measures and the subjective experience of opioid-induced constipation. The subjective experience of opioid-induced constipation may be influenced by treatment expectations. While most trials control for treatment expectations through blinding, success rate is generally low. This study aimed to explore the association between objective measures and the subjective experience of opioid-induced constipation, while considering blinding success and treatment expectations, and other psychological factors. Methods Data from a randomized, double-blinded, placebo-controlled crossover trial including 21 healthy male participants was analyzed. Participants received either placebo, tapentadol, or oxycodone (in equipotent doses) for 14 days. They were assessed on objective and subjective measures of opioid-induced constipation (gastrointestinal transit time and the Patient Assessment of Constipation-Symptoms questionnaire, respectively), treatment guesses to indicate blinding success, and psychological factors. Results There was a strong association between objective and subjective measures of opioid-induced constipation when participants were treated with oxycodone (r=0.676, p=0.006). Furthermore, participants were able to guess that they received active treatment when treated with oxycodone (p<0.001), suggesting that treatment expectations may have influenced the subjective experience of symptoms. Finally, patterns of moderate associations between opioid-induced constipation and other psychological factors emerged, although none reached significance (p>0.05). Conclusions Results indicate that treatment expectations could play an important role in the subjective experience of opioid-induced constipation, and support the importance of assessing blinding success in study trials. Besides expectations, other psychological factors may be associated with opioid-induced constipation.