Doxepin and diphenhydramine-lidocaine-antacid mouthwash minimally better than placebo for radiotherapy mucositis pain

Reference

Sio TT, Le-Rademacher JG, Leenstra JL, et al. Effect of doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash vs placebo on radiotherapy-related oral mucositis pain. The Alliance A221304 randomized clinical trial. JAMA 2019;321(15):1481-1490.

Synopsis

These investigators identified 275 patients, 18 years or older, undergoing radiotherapy for head and neck cancer. The patients had oral mucositis pain rated at least 4 on a scale of 0 to 10 (where 0 = no pain and 10 = the worst imaginable pain). Patients randomly received (concealed allocation assignment) either (1) doxepin mouthwash; (2) a composition mouthwash of diphenhydramine, lidocaine, and antacid; or (3) placebo mouthwash, administered every 4 hours for up to 7 days. Patients were masked to treatment group assignment, and self-assessed pain using a combination score based on 2 pain questionnaires. The minimal clinically important predetermined difference was a 3.5-point change in pain score. Complete follow-up occurred for all patients at 28 days, with 83% of patients completing the treatment per protocol. Using per-protocol analysis, total pain during the first 4 hours after mouthwash treatment decreased by a between-group difference of 2.9 points for doxepin vs placebo and 3.0 for diphenhydramine-lidocaine-antacid vs placebo. No significant group differences occurred in additional analgesic use or in patient preference for continued therapy. The patients who used doxepin mouthwash reported higher rates of drowsiness, unpleasant taste, and stinging/burning.