Methods: PubMed, Scopus, Web of Science, and the Cochrane Central Register of Controlled Trials were systematically searched. Reference lists from the latest systematic reviews (2015 to 2020) on BMS treatment in the PubMed, Scopus, Web of Science, and Cochrane Library databases were also scrutinized. Randomized controlled trials (RCTs) or clinical controlled trials (CCTs) in English were considered eligible. Trials on photobiomodulation were excluded to avoid redundancy with recent publications. Risk of bias was established through the Cochrane Risk of Bias tool for RCTs and the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool for CCTs.
Results: This review included 27 RCTs and 6 open clinical trials (OCTs) describing 14 different nonpharmacologic interventions. Eleven trials experimented with 600 to 800 mg/day of alpha-lipoic acid for 30 to 120 days, with 7 placebo-controlled studies showing significant pain relief. Four trials tested topical and systemic capsaicin for 7 to 30 days, with 2 placebo-controlled studies revealing significant efficacy.
Four of the 5 trials testing acupuncture offered favorable evidence of pain relief. Two trials reported significant pain relief after a 2- to 3-month regimen with tongue protectors and showed no difference after aloe vera addition. Short-term pain relief was reported in anecdotal placebo-controlled trials deploying tocopherol, catuama, ultramicronized palmitoylethanolamide, group psychotherapy, cognitive therapy, and repetitive transcranial magnetic stimulation of the prefrontal cortex. Most therapies were safe.
Conclusion: Evidence was collected from highly biased, short-term, heterogenous studies mainly focused on BMS-related pain, with scarce data on quality of life, psychologic status, dysgeusia, and xerostomia. Long-term effectiveness of nonpharmacologic treatments should be further investigated, with a more rigorous, bias-proof study design.