Background and Aims Neuropathic pain (NP) in head and neck cancer (HNC) patients represents a therapeutical challenge. Most of the studies concerning NP-medication are conducted in diabetic neuropathy or postherpetic neuralgia and limited to non-cancer pain. Regarding the cancer therapy-related-NP, most of them do not focus on HNC patients. This review aimed to identify the studies about systematically administered medication for NP in HNC patients under radiotherapy/chemoradiotherapy.

Methods A systematic literature search was performed, following the PRISMA guidelines, in PubMed, Cochrane Library, Web of Science and ClinicalTrials.gov on 30 October 2021. The MeSH terms were “head and neck cancer” OR “tumor” AND “neuropathic pain” AND “medication” AND “radiotherapy.” Cochrane Collaboration tool was used for quality assessment.

Results The search identified 432 articles; 3 more were identified after searching the reference lists of the retrieved articles. Ten articles met the inclusion criteria and were included in this review, concerning pregabalin(1), nortriptyline(1), methadone(1), ketamine(1) and gabapentin(6). Statistically significant results in pain reduction compared to placebo or standard pain medication were found in the studies concerning pregabalin(p=0.003), nortriptyline(p=0.04), methadone(p=0.03), ketamine(p=0.012) and in 2 out of 6 gabapentin studies(p<0.004). Two of the studies had no comparison arm.

Conclusions Interventions including pregabalin, nortriptyline, methadone, ketamine and gabapentin, were found to provide pain relief. While there is a plethora of pharmacological interventions available, only a few studies have been conducted regarding the pharmacological management of therapy-related-NP in HNC patients, including a small range of interventions. More studies should be conducted regarding the pharmacological approaches in HNC therapy-related-NP and the specific treatment algorithms.