Nocebo response in dentistry: A systematic review and meta-analysis of adverse events in analgesic trials of third molar removal

TY - JOUR

T1 - Nocebo response in dentistry

T2 - A systematic review and meta-analysis of adverse events in analgesic trials of third molar removal

AU - Watanabe, Takeshi

AU - Sieg, Mette

AU - Lunde, Sigrid Juhl

AU - Persson, Mads

AU - Taneja, Pankaj

AU - Baad-Hansen, Lene

AU - Pigg, Maria

AU - Vase, Lene

PY - 2023/4

Y1 - 2023/4

N2 - BACKGROUND: The nocebo response refers to the phenomenon where nonspecific factors, including negative verbal suggestion and treatment expectations, cause adverse events (AE) following a placebo treatment. Nonspecific 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.

AB - BACKGROUND: The nocebo response refers to the phenomenon where nonspecific factors, including negative verbal suggestion and treatment expectations, cause adverse events (AE) following a placebo treatment. Nonspecific 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.

KW - analgesics

KW - long term adverse effects

KW - nocebo effect

KW - oral surgery

KW - pain

KW - third molar

KW - Analgesics

KW - Nocebo Effect

KW - Humans

KW - Dentistry

KW - Molar, Third

UR - http://www.scopus.com/inward/record.url?scp=85147213142&partnerID=8YFLogxK

U2 - 10.1111/joor.13414

DO - 10.1111/joor.13414

M3 - Review

C2 - 36648379

SN - 0305-182X

VL - 50

SP - 332

EP - 342

JO - Journal of Oral Rehabilitation

JF - Journal of Oral Rehabilitation

IS - 4

ER -