Regarding the problems and complications of oral mucositis, prevention and treatment of this complication in patients undergoing chemotherapy and head and neck radiotherapy is very important.
Timely treatment of this condition will relieve pain, improve nutrition, reduce the need for analgesics, antimicrobials and increase the patient's ability to tolerate the treatment, and thus it will raise the life expectancy of the patients.
The aim of this study was to investigate the effect of doxepin 0.5% mouthwash in comparison with perisca mouthwash on reducing the pain of oral mucositis in patients with head and neck cancer after radiotherapy and chemotherapy.
This randomized controlled trial resulted in both mouthwashes decreased pain score of mucositis during the study. This study has shown that doxepin had better taste but led to drowsiness. Doxepin reduces pain through Na channel blocking and NMDA receptors regulating. The precise analgesic mechanism of persica is unclear, but since in clinical trials effect of Salvadora Persica has been neutralized by naloxone, its effect may be applied through opiate receptors.
Recent studies against this study have focused on persica’s effectiveness in preventing mucositis. For example, the results of a study by Zakaria and Abdul Rahim showed that saladora persica blue extract reduced the incidence of mucositis caused by 5FU in rats (18). In a study by Abedipour et al aiming at comparing the effect of persica and chlorhexidine mouthwash on preventing mucositis in 30 patients aged 14–50 years with acute myeloblastic leukemia and acute lymphoblastic leukemia under chemotherapy showed that persica and chlorhexidine mouthwash were equally effective in preventing stomatitis. The researches recommended persica, regarding the side effects of chlorhexidine (19).
In a study conducted by Hoor and Ahmed et al with the aim of investigating the analgesic effect of persica at doses of 700,500,300 mg / kg in compare with aspirin on 21 mice, it was concluded that persica would be effective in reducing the pain at doses of 500 and 700 mg / kg after 210 minutes (20).
The aim of this study was to investigate the effect of doxepin mouthwash in comparison with perisca mouthwash on reducing the pain of oral mucositis.
In 2001, Epstein et al conducted a study to evaluate pain relief from oral mucositis after oral use of doxepin 0.5% in cancer patients. Researchers evaluated oral pains before taking mouthwash and 4 hours after it by Visual Analog Scale (VAS). In more than 50% of patients, pain relief was observed more than 3 hours after taking mouthwash, and this pain reduction did not return to the initial level until the end of 4 hours.
In the current study, the pain did not return to the initial level until the end of 24 hours.
Also, this oral mouthwash had acceptable taste from the viewpoint of patients and they did not report burning sensation which was consistent with the result of present study (21).
In a study by Epstein et al in 2006, aiming at examining the analgesic effect of doxepin 31.4%, patients reported inappropriate feelings and mild burning, which has not been reported in the present study(22).
The results of this study showed that pain induced by mucositis decreased by using doxepin, which were consistent with study by Epstein et al (22)and Leenstra et al (17).Study of Epstein et al (22)evaluated the analgesic effect of doxepin 5 mg / ml on 51 patients by using it 4 times and the study of Leenstra et al (17)was performed on 55 patients to compare the effect of using doxepin and placebo in a single dose and pain level was measured at 5,15,30,60 and 120 minutes. According to the findings of this study it seems that dexpine mouthwash play a very effective role in mucositis pain control.
Also, in the persica group, pain decreased after 30 minutes, then reached the plateau and did not return to the base after 4 hours. Patients used mouthwash two more times in a day and pain did not return to the initial level for 24 hours.
Comparison of the two groups showed that the analgesic effect did not differ significantly in 5, 15, 30, 120, 240 minutes and 24 hours later in both groups, and persica could reduce pain in the patients.
It is worth noting that reduction of mucositis pain in both groups was significant in favor of doxepin at 60 minutes.
This is probably due to the anesthetic effect of doxepin mouthwash, which lasted about one hour in patients. After eliminating the anesthetic effect of doxepin mouthwash, the analgesic effects of the two groups were not significant at 120 and 240 minutes.
The burning sensation in the doxepin group was significantly higher than persica group at 5 and 15 minutes.
In the current study, patients in doxepin group did not report change in their taste after 4 hours, which indicates that the analgesic effect of this drug was not due to local anesthesia. This conclusion was confirmed by the study of Epstein et al(23). Patients in the persica group also did not report a change in their taste, which was contrary to the results of the Salehi study, which 40% of the patients reported change in their taste(19).
The possible cause of this different might be related to the duration of the use of persica, which was 4 weeks in the study of Salehi and it was only 1 day in the current study.
In this study 50% of patients in doxepin group suffered from severe drowsiness and 49.4% of them reported mild drowsiness. This conclusion was confirmed by the study of Epstein et al(21–23); patients in persica group did not report this condition.
Despite the introduction of various drugs and methods, there is no standard treatment for oral mucositis (24). But according to the findings of this study, mentioned mouthwashes had beneficial effects in the control of oral mucositis.
This study had several limitations such as finding sufficient number of patients due to pursuing critically ill patients.