The report is a product of the VA/HSR Evidence Synthesis Program.

Chronic Xerostomia Management Following Radiation Therapy: A Systematic Review

Takeaway: Xerostomia (the sensation of mouth dryness) is a frequent complication of radiation treatment for head and neck cancers (HNC). This review found that the evidence for most treatments to improve post-radiation xerostomia in patients with HNC was heterogeneous in terms of interventions compared and reported outcomes. Across all interventions, the evidence was strongest for the effectiveness of pilocarpine tablets for xerostomia symptoms (low confidence), but not functional outcomes (low confidence). For all other outcomes and interventions (e.g., cevimeline [a drug to treat dry mouth symptoms], adipose tissue-derived mesenchymal stem/stromal cells [stem cells found in fat tissue that can help repair or replace damaged tissue], acupuncture), there was either no evidence of a difference, with mostly low confidence, or insufficient evidence. Future studies should compare well-defined interventions to placebo when possible or to other well-defined interventions when that is not possible; clearly and completely report findings; explore the heterogeneity of responses to pilocarpine and evaluate treatment strategies for patients who do not respond; and examine the psychosocial factors that influence outcomes, as well as the impact of psychosocially oriented treatment strategies on the experience of living with post-radiation xerostomia. The field would also benefit from well-designed studies of low-risk and widely available treatments, such as saliva substitutes.

Head and neck cancers (HNC) are common among Veterans. Xerostomia (the sensation of mouth dryness) is a frequent complication of radiation treatment for HNC. In response to a request from the VHA Oncology Clinical Nutrition Work Group, HSR’s Evidence Synthesis Program (ESP) Center in Providence, RI, reviewed the evidence on the effectiveness of treatments for post-radiation chronic xerostomia in patients with HNC. ESP investigators focused on outcomes of xerostomia symptoms, nutrition, body weight, function, quality of life, and adverse events. To identify relevant articles, the ESP team searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to July 9, 2025. Additional citations were identified from hand-searching reference lists of related systematic reviews.

Summary of Findings

• This review identified 40 randomized controlled trials that explored the effectiveness of treatments for xerostomia. Most of the trials were small, with unclear reporting and incomplete evaluation of clinically important outcomes. Few of the trials directly compared interventions.
• The most frequently reported interventions were saliva substitutes, followed by pilocarpine (a drug to treat dry mouth symptoms), electric nerve stimulation, cevimeline (a drug to treat dry mouth symptoms), acupuncture, adipose tissue-derived mesenchymal stem/stromal cells (stem cells found in fat tissue that can help repair or replace damaged tissue), and other therapies.
• Across all interventions, the evidence was strongest for the effectiveness of pilocarpine tablets for xerostomia symptoms (low confidence), but not functional outcomes (low confidence). Pilocarpine lozenges and spray are no more effective than placebo to improve symptoms (low and moderate confidence, respectively).
• Acupuncture is not better than standard oral hygiene to improve xerostomia symptoms or quality of life (low confidence for both).
• For adipose tissue-derived mesenchymal stem/stromal cells, there is no evidence of a difference for xerostomia symptom outcomes (moderate confidence) or functional outcomes (low confidence) compared to placebo.
• Cevimeline is not better than placebo to improve xerostomia symptoms or functional outcomes (low confidence for both).
• Laser therapy is not better than sham to improve xerostomia symptoms (low confidence).
• Data were insufficient for nutrition, body weight, and adverse event outcomes for these interventions, as well as for interventions such as chewing gum, electrical stimulation, herbal treatments, and saliva substitutes.

Implications

Across all interventions, the best evidence was for pilocarpine. For all other interventions and outcomes, there was either no evidence of a difference, with mostly low confidence, or insufficient evidence. The breadth of interventions across the trials indicates interest in identifying effective treatments for xerostomia. Future studies should improve upon existing literature by replicating evaluations of well-defined treatments and comparators and their effects on multiple standard patient-centered outcomes.

Limitations

Numerous studies had small sample sizes, and data reporting was often unclear and incomplete. Studies were highly variable in the interventions evaluated, the outcomes assessed, and the specific measures applied. This lack of consistency precluded meta-analysis and resulted in mostly insufficient and low-certainty evidence. The studies were generally short-term, with most not extending beyond six months. Together with the general lack of replication of studies across trials, the overall effectiveness of the evaluated interventions for xerostomia is unclear.

Future Research

Future studies on interventions for xerostomia in HNC patients should compare well-defined interventions to placebo when possible or to other well-defined interventions when that is not possible, and should clearly and completely report findings. Future studies should also explore the heterogeneity of responses to pilocarpine and evaluate treatment strategies for patients who do not respond. Additionally, future research should examine the psychosocial factors that influence outcomes, and the impact of psychosocially oriented treatment strategies on the experience of living with post-radiation xerostomia. The field would benefit from well-designed studies of low-risk and widely available treatments, such as saliva substitutes.

Citation:

Rieke K, Epstein-Lubow E, Rudolph J, et al. Chronic Xerostomia Management Following Radiation Therapy: A Systematic Review. Washington, DC: Evidence Synthesis Program, Health Systems Research, Office of Research and Development, Department of Veterans Affairs. VA ESP Project #22-116; 2026.

To view the full report, go to vaww.hsrd.research.va.gov/publications/esp/xerostomia.cfm (This report is available via intranet only.)

How can VA leadership work with the ESP? Nominations for systematic review topics may be submitted to the program at any time. When you submit a topic nomination form, ESP Coordinating Center staff will work with you to determine the appropriate research approach and ESP product to address your questions of interest. Topics are selected and assigned to an ESP Center based on program capacity and alignment with VA national goals.

This Management Brief is provided to inform you about recent HSR findings that may be of interest. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs. If you have any questions or comments about this Brief, please email CIDER. The Center for Information Dissemination and Education Resources (CIDER) is a VA HSR Resource Center charged with disseminating important HSR findings and information to policy makers, managers, clinicians, and researchers working to improve the health and care of Veterans.

This report is a product of VA/HSR's Evidence Synthesis Program (ESP), which was established to provide timely and accurate synthesis of targeted healthcare topics of particular importance to VA managers and policymakers, and to disseminate these reports throughout VA.

See all reports online.