Abstract
INTRODUCTION: Temporomandibular Disorders (TMDs) encompass a set of conditions affecting the masticatory muscles and the temporomandibular joint (TMJ), with an impact on both functionality and individuals' quality of life. Myalgia is a diagnosis of TMD with multifactorial etiology, and treatment strategies aim primarily to relieve pain and restore function. Pharmacological therapy is commonly considered a second-line option, thus complementing conservative measures. OBJECTIVES: Assess the efficacy of pharmacological interventions in the management of myalgia associated with temporomandibular disorders, in adolescents and adults, while exploring differential effects across TMD subtypes through subgroup analyses, using a systematic review and meta-analysis of randomized controlled trials (RCTs). MATERIALS AND METHODS: A systematic review with meta-analysis was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions and reported following the PRISMA 2020 statement. Seventeen randomized controlled trials (RCTs) published between 2018 and 2024 were included. Pharmacological interventions such as nonsteroidal anti-inflammatory drugs, corticosteroids, muscle relaxants, antidepressants, and intra-articular injectables-were compared with placebo or other active treatments. The primary outcomes were pain intensity (Visual Analog Scale, VAS) and maximum interincisal opening (MIO) unassisted. RESULTS AND DISCUSSION: A total of 1,128 participants were analyzed across 25 treatment arms. Pharmacological interventions were associated with a significant reduction in pain (SMD = -0.68; 95% CI: -1.09 to -0.26; p < 0.001) and an improvement in MIO (SMD = 0.51; 95% CI: 0.20 to 0.82; p < 0.001). Subgroup analyses indicated that interventions were more consistent and effective in arthralgia-only populations, showing lower heterogeneity and a more predictable therapeutic response, whereas myalgia-only populations exhibited smaller and less consistent benefits. Conservative therapies demonstrated a consistent advantage, thus aligning with international recommendations that prioritize such approaches. Subgroup analyses demonstrated more consistent and homogeneous effects in arthralgia-dominant populations, whereas myalgia-only studies showed greater heterogeneity and less predictable responses. CONCLUSION: Pharmacological therapy provides a moderate overall beneficial effect in reducing pain and improving mandibular function in TMD, with stronger and more consistent evidence in arthralgia-dominant populations, while myalgia-related outcomes remain more variable, thus indicating the need for tailored treatment strategies. Further high-quality RCTs with standardized protocols are needed.