Background: Salivary gland dysfunction is a predictable side effect of radiotherapy to the head and neck region. Pilocarpine hydrochloride (a choline ester) is licensed in many countries for the treatment of radiation-induced salivary gland dysfunction. Other parasympathomimetics have also been used 'off licence' in the treatment of this condition.
Objectives: To determine the efficacy and tolerability of parasympathomimetic drugs in the treatment of radiation-induced salivary gland dysfunction.
Search strategy: A detailed search strategy was developed for MEDLINE, and adapted for other databases (Cochrane Pain, Palliative and Supportive Care Group Register; Cochrane Oral Health Group Register; The Cochrane Controlled Trials Register; EMBASE; CINAHL; SIGLE; Dissertation Abstracts). The reference lists of identified studies, review articles and radiotherapy textbooks were checked for additional studies. Relevant pharmaceutical companies, clinical investigators, and professional organizations/journals were also contacted about additional studies.
Selection criteria: The selection criteria for the review were: 1) randomised controlled trials; 2) patients suffering from radiation-induced salivary gland dysfunction; 3) patients treated with parasympathomimetic drugs; and 4) assessable data available on primary outcome measures.
Data collection and analysis: The two review authors independently collected data from the full text version of relevant papers including: 1) citation details; 2) patients; 3) interventions; 4) assessments; 5) outcomes (i.e. efficacy, tolerability); and 6) quality issues. We were unable to perform a meta-analysis, due to a lack of appropriate data.
Main results: Only three studies, involving a total of 298 patients, fulfilled the entry criteria for the review. All three studies involved the use of pilocarpine hydrochloride. The data suggest that pilocarpine hydrochloride was more effective than placebo, and at least as effective as artificial saliva in those participants that responded. The response rate was 42 to 51%. The time to response was up to 12 weeks. The side effect rate was high, and side effects were the main reason for withdrawal (six to 15% patients taking 5 mg tds). The side effects were usually the result of generalised parasympathomimetic stimulation (e.g. sweating, headaches, urinary frequency, vasodilatation). Response rates were not dose dependent, but side effect rates were dose dependent.
Authors' conclusions: There is limited evidence to support the use of pilocarpine hydrochloride in the treatment of radiation-induced salivary gland dysfunction. Currently, there is little evidence to support the use of other parasympathomimetic drugs in the treatment of this condition. Available studies suggest approximately half of patients will respond, but side effects to responders can be problematic. Adverse effects are dose dependent therefore it is important to keep dose to 5 mg tds.