2 kinds of mouthwash reduce oral pain after radiotherapy for head and neck cancer

  • Sio TT & al.
  • JAMA
  • 16 Apr 2019

  • International Clinical Digest
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  • Doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash significantly reduced oral mucositis-related pain within 4 hours of administration compared with placebo mouthwash in patients undergoing radiotherapy for head and neck cancer.

Why this matters

  • The study offers the first evidence that diphenhydramine-lidocaine-antacid mouthwash is effective for short-term reduction of radiotherapy-related oral mucositis-related pain.

Study design

  • 3-group, double-blind, placebo-controlled phase 3 randomized trial.
  • 275 patients with head and neck cancer radiotherapy-related oral mucositis pain were randomly assigned to doxepin mouthwash or diphenhydramine-lidocaine-antacid mouthwash or placebo.
  • Funding: National Cancer Institute.

Key results

  • Compared with placebo, total pain during the first 4 hours significantly decreased in the doxepin mouthwash group (8.7 vs 11.6 points; P=.02) and in the diphenhydramine-lidocaine-antacid mouthwash group (vs 11.7 points; P=.004).
  • During the first 4 hours, doxepin mouthwash was associated with higher incidence vs placebo in terms of:
    • total drowsiness (difference, 1.5 points; P=.03),
    • unpleasant taste (difference, 1.5 points; P=.002), and
    • stinging or burning (difference, 4.0 points; P<.001>
  • Grade 3 adverse event rate was 4% with doxepin mouthwash, 4% with diphenhydramine-lidocaine-antacid mouthwash, and 2% with placebo.
  • 6% of patients experienced fatigue with doxepin mouthwash, and none with diphenhydramine-lidocaine-antacid mouthwash.


  • Direct comparison of doxepin and diphenhydramine-lidocaine-antacid mouthwash was not available.

 Coauthored with Antara Ghosh, PhD