The Role of Pharmacogenomics in Optimizing Ketamine Therapy for Post-Amputation Pain.

Context and objective: Post-amputation pain (PAP) is an umbrella term that includes residual limb pain (RLP) and phantom limb pain (PLP), posing a significant challenge to recovery and quality of life after limb loss. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has gained interest for its potential to manage PAP, particularly in refractory cases. This narrative review explores the efficacy of ketamine for PAP and the emerging role of pharmacogenomics in guiding its use.

Methods: A literature review of PubMed, Embase, and Cochrane databases was conducted, focusing on clinical trials, systematic reviews, and genetic influences on ketamine metabolism and response. Studies suggest that perioperative ketamine can reduce PAP severity and opioid use. However, outcomes vary, with some patients experiencing transient relief and others achieving prolonged benefit.

Results: This variability may be linked to genetic differences in CYP2B6, CYP3A4/5, COMT Val158Met, SLC6A2, and KCNS1, which affect ketamine's metabolism, efficacy and side effect profile. Understanding these pharmacogenomic factors could enable more personalized and effective ketamine therapy.

Conclusion: Despite its promise, inconsistent dosing regimens and limited integration of genetic data hinder standardization. Further research into genotype-guided ketamine protocols may improve treatment outcomes and support precision analgesia in amputee care.