Percutaneous Drug Delivery to the Masticatory System: A Systematic Review and Analysis of Randomized Clinical Trials

Background: Due to the high frequency of pain associated with the masticatory system, in addition to the use of physiotherapy, it is sometimes beneficial to introduce percutaneous pharmacology. This is an example of a non-invasive alternative to the traditional route of administration, which can be highly effective and limit the risk of many side effects. The aim of this study is to evaluate the efficacy and safety of transdermal drug application by patients with temporomandibular disorders (TMD). Methods: A review of randomized controlled trials retrieved from PubMed, ACM, BASE, Scopus, Cochrane, and Google Scholar on 23 October 2025 was performed using the PRISMA Checklist. Studies that evaluated transdermal drug administration for masticatory system-related conditions were included. Trials involving interventions such as muscle punctures or any systemic treatments were excluded. The revised Cochrane tool (RoB 2) was used to assess the risk of bias. A statistical analysis of the effect of such therapy on pain and its influence on changes in mandibular abduction was performed. Results: A total of nine articles meeting the inclusion criteria were included, with a total of 390 participants. The risk of bias assessment indicated that most articles were of low risk of bias (6/8), while two were assessed as "some concerns". The review found a significant reduction in pain on the visual analog scale (VAS) for selected active substances (p < 0.05). The greatest pain reduction occurred when 1.46% cannabidiol was used. There are few results regarding the effect of this method on jaw opening, and the results obtained are comparable for the placebo group, which was related to the application method. Conclusions: The results of this systematic review are promising and indicate the probable effectiveness of this method, but due to some limitations, this topic requires further investigation.