The effects of licorice containing diphenhydramine solution on recurrent aphthous stomatitis: A double-blind, randomized clinical trial.

Objectives: The aim of this study was to compare the efficacy of the diphenhydramine solution (DS) and diphenhydramine-containing glycyrrhiza glabra (DSG) in the treatment of recurrent aphthous stomatitis (RAS).

Design: It was a double-blind randomized clinical trial that was conducted from July to September 2018 at the Faculty of Dentistry, Birjand University of Medical Sciences, Birjand, Iran.

Intervention: DSG was made by adding 5% hydroethanolic extract of licorice to the diphenhydramine elixir. A total of 70 patients diagnosed with RSA were randomly assigned to the DS and DSG groups, each containing 35 patients. Participants were instructed to swish 3 ml of either solution around their mouth for about three minutes four times a day (at least 20 min before each meal and before bedtime) until the complete healing of the oral lesions.

Main Outcome Measures: The primary outcome of this study was to assess the severity of pain prior to the intervention and on the first, third, and fifth days of it. This was done using the visual analog scale (VAS). The duration of wound healing was also measured through photography. The secondary outcome was to record the adverse effects of the intervention. This trial was registered at the Iranian Registry of Clinical Trials under number IRCT20180407039213N1.

Results: The average pain score before the treatment in the DS and DSG groups was 8. 1 ± 1.17 and 7.97 ± 1.72, respectively, and there was apparently no significant difference between them. However, there was a significant difference between the two groups in terms of the average pain scores on the first (7 ± 1.28 versus 5.31 ± 1.28), third (4.02 ± 1.8 vs. 2.86 ± 1.56) and fifth days (1.71 ± 1.69 vs. 0.54 ± 1.31) of the intervention. Indeed, DSG significantly reduced the average wound healing duration by 1.5 days, as compared to DS (P = 0.0001). No adverse effects were observed with the intervention.

Conclusion: According to our results, DSG appeared to be more effective in treating RAS than DS alone.

Trial Registration: The trial was registered at Iranian Registry of Clinical Trials before the enrolment of the first patient on June 29, 2019 (registration no: IRCT20180407039213N1, http://www.irct.ir/trial/31497).