Placebo and nocebo response magnitude on temporomandibular disorder-related pain: A systematic review and meta-analysis

Objectives The aim of this systematic review (SR) was to answer the following question: "In adult patients with temporomandibular disorder (TMD)-related pain, what is the placebo or nocebo effect of different therapies?" Methods A SR was performed with randomised clinical placebo-controlled trials on diagnosed painful TMD studies from five main databases and from three grey literature. Studies included must have sample older than 18 years, with painful TMD, which diagnosis was done by Research Diagnostic Criteria (RDC/TMD) or Diagnostic Criteria (DC/TMD). Results Out of 770 articles obtained, 42 met the inclusion criteria for qualitative and 26 for quantitative analysis. Meta-analysis indicated mean variation on pain intensity for placebo therapy was higher on laser acupuncture with 45.5 mm point reduction, followed by avocado soya bean extract with 36 mm and amitriptyline 25 mg with 25.2 mm. Laser showed a 29% of placebo effect, as well medicine with 19% and other therapies with 26%. Possible nocebo effect of 8% pain increase was found for intra-articular injection of Ultracain. Conclusions Based on the available data, the placebo response could play a major effect on TMD pain management and may be responsible from 10% to 75% of pain relief. Laser acupuncture, avocado soya bean and amitriptyline promoted the higher placebo effect. Possible nocebo effect was found only for Ultracain injection with 8%. Clinical Relevance Clinicians could apply such evidence to optimise pain management and judgement about treatment efficacy, and researches may find it useful when designing their investigations.