Pregabalin for Radiation-Induced Neuropathic Pain in Head and Neck Cancer: A Randomized Controlled Trial

Introduction: Radiotherapy for head and neck cancer frequently induces severe neuropathic pain, significantly impairing patient quality of life and adherence to treatment. Despite this high clinical burden, effective prophylactic interventions remain largely unestablished. Therefore, this randomized, double-blind, placebo-controlled trial aimed to evaluate the efficacy of prophylactic pregabalin in preventing radiation-induced neuropathic pain. Material and methods: This randomized, double-blind clinical trial evaluated 60 patients with head and neck cancer divided into two equal groups of 30 using convenience sampling and the Cochran formula. Conducted at Shahid Madani Hospital, the procedure involved administering prophylactic pregabalin or a comparator during radiotherapy. Serial assessments monitored neuropathic pain trajectories, rescue analgesic consumption, and safety profiles throughout the intervention and follow-up periods. Results: Prophylactic pregabalin significantly attenuated radiation-induced neuropathic pain progression (week 6 DN4: 4.1 plus minus 1.0 vs 7.1 plus minus 1.2, P<0.001) and reduced cumulative opioid consumption (285.4 plus minus 48.2 mg vs 542.8 plus minus 76.5 mg, P<0.001) across both sexes without significant between-sex divergence. Conclusion: Prophylactic pregabalin administration effectively mitigates radiotherapy-induced neuropathic pain and substantially reduces opioid dependency in head and neck cancer patients. Demonstrating robust sex-independent efficacy and manageable tolerability, pregabalin serves as a valuable adjunct in combined-modality oncologic care, optimizing patient quality of life during aggressive radiation therapy.