Epstein, J.B., Epstein, J.D., Epstein, M.S., Oien, H., & Truelove, E.L. (2008). Doxepin rinse for management of mucositis pain in patients with cancer: One week follow-up of topical therapy. Special Care in Dentistry, 28(2), 73–77.

To determine the impact of repeated dosing with doxepin rinse over the course of one week in patients with oral mucositis

Patients were instructed to rinse the oral cavity for 1 minute with 5 mL doxepin suspension (5 mg/mL) and then spit it out. Patients were to continue using the rinse as needed, 3–6 times per day, for the following week until their second visit and assessment. Standard of care for mucositis also was used during this time. Subjects used diaries to record analgesic use and mouth rinses.

• The study reported on 9 patients, 3 women and 6 men, with a median age of 41 years.
• Patients were receiving radiation therapy, chemotherapy, hematopoietic stem cell transplantation (HSCT), or a combination of these for head and neck cancer.
• All patients had painful oral mucositis.

The study was conducted at a single site, outpatient setting in Canada.

This was a nonrandomized, unblinded, uncontrolled, open-label study.

• Data was compiled in Microsoft Excel. Statistical analysis was conducted using SAS 9.0 for Windows. Frequencies, medians, and ranges were used to report subject characteristics.
• Oral pain was graded using a visual analog scale (VAS) (0 = no pain, 10 = worst pain). Oral pain when eating and without function was graded prior to oral rinse and at 5 minutes, 15 minutes, 1 hours, 2 hours, 3 hours, and 4 hours following doxepin rinse.
• A VAS was used to report the taste of the rinse, discomfort, and fatigue.
• An Oral Mucositis Assessment Scale (OMAS) was used.
• Patients were asked to record in a diary estimates of their average pain up to four hours after using the rinse.

Statistically significant reductions in pain scores were reported for two hours following doxepin rinse during the initial visit (p < 0.05). Patients recalled that their pain significantly dropped within 5 minutes of rinsing over the week of repeated dosing (p < 0.05). At the follow-up visits, subjects reported statistically significant pain reduction 5 minutes after doxepin rinsing (p < 0.05). No changes were reported in systemic analgesics used during the study week despite the increasing severity of mucositis. No significant differences were found in mucositis scores over time.

Doxepin rinsing in addition to usual oral care produced reduced intensity of pain levels but no apparent difference in mucositis severity. No firm conclusions can be drawn from this extremely small sample.

• The sample size was small.
• Risk of bias exists because this was not a randomized, controlled, blinded study
• The standard care protocol, which also was used for oral care, was not described.

The doxepin rinse was well tolerated, and the results warrant a larger, randomized, controlled clinical trial.