Health-related quality of life after ketamine or esketamine treatment for chronic pain: a review of randomized controlled trials.

Chronic pain, lasting over three months, significantly impairs patients' health-related quality of life (HRQoL) due to its impact on physical, psychological, and social well being. Given the limitations and risks associated with opioid use, there is growing interest in alternative analgesics. Ketamine and its S-enantiomer, esketamine, as NMDA receptor antagonists, are becoming important treatments for central sensitization. However, evidence regarding their direct positive effect on HRQoL in chronic pain patients remains sparse. This systematic review was conducted following Cochrane standards and the PRISMA framework. The search included only randomized clinical trials (RCTs) in adult patients focusing on HRQoL measures following ketamine or esketamine treatment for chronic pain. Methodological bias was assessed using the Cochrane RoB2 tool.

Results

The systematic search yielded five eligible RCTs involving 405 patients with diverse chronic pain conditions. The studies were mixed and heterogeneous due to various routes of administration and different HRQoL instruments. Two studies reported a significant improvement in HRQoL (for central pain/low back pain); two found no difference (oncological/neuropathic pain); and one reported a worsening of HRQoL in palliative care cancer patients, linked to adverse events.

Conclusion

The significant heterogeneity across the selected RCTs (pain types, regimens, routes, and HRQoL tools) makes meta-analytic synthesis unfeasible. The results on the impact of ketamine and esketamine on HRQoL in chronic pain patients are inconsistent, ranging from improvement to worsening. Future research must prioritize HRQoL as a primary outcome and standardize protocols to establish stronger, generalizable evidence.