PURPOSE: This systematic review aimed to assess the effectiveness of prophylactic gabapentin in managing pain related to mucositis developed in patients with head and neck tumors undergoing chemoradiation. METHODS: An electronic search of indexed databases, including PubMed, EMBASE, Scopus, ISI Web of Knowledge, Cochrane Library, and Google Scholar, was performed without time restriction until April 2024. Risk of Bias (RoB) assessment was conducted using the Cochrane tool. This study was registered in the PROSPERO database (CRD42024550242). RESULTS: An initial electronic and manual search revealed 1,786,350 manuscripts. Five randomized controlled trials (RCTs) were included following the eligibility criteria. In one study, gabapentin was statistically significant in reducing pain
however, a positive trend was observed in three studies with no statistical significance. Four studies showed a trend either in reduction or a delay in opioid usage. The overall quality of life was significantly improved in one study, whereas a positive trend was observed in two studies and neutral in two. Future standardized studies with larger sample sizes are required to understand better the effectiveness of gabapentin in patients undergoing cancer management of the head and neck region. CONCLUSION: Overall, there was a positive trend in reducing oral mucositis-related pain in patients undergoing chemoradiation of the head and neck region, with only one study reaching statistical significance. Gabapentin also demonstrated effectiveness in reducing opioid dependency, delaying opioid initiation, and managing early pain, with tolerable side effects in most studies and improving the overall quality of life. Future studies with standardized protocols and higher sample sizes are required to validate these results further.