A systematic review and meta-analysis of single-application topical doxycycline for recurrent aphthous stomatitis

Recurrent aphthous stomatitis (RAS), an oral mucosal pathosis, can interfere with patients' quality of life, mainly due to its recurrent nature. The etiology of RAS remains unclear and its management is challenging. This systematic review and meta-analysis were performed to assess the efficacy of a single topical application of doxycycline to treat RAS. Online search of the Scopus, Medline (via PubMed), Embase and Google Scholar databases was performed from May to September 2025. Randomized controlled trials (RCTs) were selected, eligible studies were conducted for healthy patients with the primary diagnosis of RAS who received the treatment. Primary outcomes (Pain scores & healing times) were extracted. The Cochrane Collaboration risk of bias (ROB) tool was used for quality control. The data were synthesized and a meta-analysis was performed. Five RCTs were included in the systematic review and three were included in the meta-analysis. Two were excluded for insufficient sample size. The overall average healing times in the control and doxycycline groups were 2.695 ± 0.731 and 1.677 ± 0.588 days, respectively (p = 0.274). Additionally, mean pain scores in the control and doxycycline groups were 2.718 ± 0.466 and 2.039 ± 0.790, respectively (p = 0.291). However, one study revealed a significant effect in healing time (0.032). Topical doxycycline appears to have a clinical role in RAS treatment, despite the small number of available clinical studies. Further controlled clinical trials are warranted to confirm study findings.