Doxepin as an anesthetic and analgesic rinse may benefit patients receiving radiotherapy for head and neck cancer who are suffering from acute oral mucositis (OM). A new randomized controlled trial has found that doxepin rinse may result in a modest but significant improvement in mouth and throat pain over a 4-hour period after a single doxepin rinse.

“We were pleased with the results. I think it will make a difference,” said study investigator Robert C. Miller, MD, professor of radiation oncology at the Mayo Clinic in Rochester, MN. “It is roughly a 20% reduction in mouth and throat pain as reported by the patient.”

RELATED: Head and Neck Cancer Resource Center

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Dr. Miller and his colleagues conducted the study with 155 patients who were randomly assigned to doxepin oral rinse or placebo for the treatment of radiotherapy-related OM pain.1 Each patient received a single dose of doxepin rinse or placebo on day 1 and then crossed over to receive the opposite agent on a subsequent day. All patients were given pain questionnaires that they completed at baseline and then again at 5, 15, 30, 60, 120, and 240 minutes after they received the doxepin rinse or the placebo rinse.

Reduction in Pain, But Increased Drowsiness

The researchers found that the average mouth and pain score reduction was -2.0 on a scale of 0 to 10 from baseline at 30 minutes after the rinse for the doxepin-treated group compared with-1.0 for the placebo-treated group. Doxepin hydrochloride is a tricyclic antidepressant, which is known to have analgesic and anesthetic properties when delivered topically. Drowsiness is a well-documented adverse effect from taking doxepin, and so the investigators also assessed drowsiness on a numeral analog scale from 0 to 10 (0 was no drowsiness). 

The study showed that the mean drowsiness score at the 2-hour assessment was 3.9 for the doxepin-treated group compared with 2.8 for the placebo-treated group. The crossover data in the second phase of the study showed that doxepin resulted in more stinging and burning and worse taste, as well as caused increased drowsiness. Dr. Miller said the drowsiness reported in this study may be because of some systemic doxepin absorption through damaged oral mucosa, even though the rinses were limited to just 1 minute in duration.

“There were no surprises on the side effects. Because of the drowsiness, some people were taking it at night to go bed,” said Dr. Miller in an interview with

This trial is the largest placebo-controlled study to specifically test the efficacy of a rinse agent in controlling established mucositis pain, and it is the only trial to show such positive results, according to Dr. Miller. He said studies in the future need to compare doxepin rinse with other approaches that are commonly prescribed to patients receiving radiotherapy to treat head and neck cancer.