Abstract

Background: Burning mouth syndrome (BMS) is a chronic pain disorder frequently associated with clinical and psychological comorbidities, the treatment of which continues to represent a therapeutic challenge. Clonazepam is widely used in its management, although reported results vary depending on the route of administration. This review mapped how clinical–psychological characteristics were reported across clonazepam studies and explored whether outcome patterns differed by administration route within a SWiM framework. Methods: A systematic review was carried out in accordance with the PRISMA 2020 guidelines and the SWiM framework. We searched PubMed, Scopus, and Web of Science for studies up to October 2025, including clinical and observational studies evaluating the use of clonazepam in people with BMS. Therapeutic response was defined as a ≥30% reduction in baseline symptoms. Results: We included 20 studies (n = 1,042 patients; 85% women; mean age: 62 years). Patients presented with frequent systemic comorbidities, such as high blood pressure, diabetes mellitus, and thyroid disorders, along with a high prevalence of anxiety and depression. Eleven studies evaluated topical clonazepam, eight the systemic route, and one a mixed regimen. Using a vote-counting approach, topical clonazepam reported a ≥30% reduction in pain in 9 of 11 studies and ≥50% in 5 of 11; However, the studies showed substantial heterogeneity in diagnostic criteria, design, dosage, duration of treatment, pain assessment tools, and methodological quality. In this context, the results should be interpreted as a descriptive synthesis and not as definitive comparative evidence between routes of administration. Conclusion: Topical clonazepam showed a more consistent trend toward clinically meaningful symptom improvement; however, comparative effectiveness and phenotype-related effect modification cannot be inferred from the available evidence. Clinical-psychological characteristics could constitute a relevant element in therapeutic decision-making, although their value as a predictive guide requires confirmation in future studies with standardized methodologies.