Managing Chronic Pain: The Ketamine Option
CNS Drugs – October 16, 2025
Source: OpenAlex
Summary
Ketamine has shown significant promise in managing chronic refractory pain, particularly neuropathic pain, providing substantial short-term relief for many patients. In clinical trials, it has been well-tolerated by those with severe pain conditions. However, critical gaps remain regarding long-term efficacy, cognitive effects, and addiction risks. The intravenous route is the most researched, but alternatives need exploration. As a non-first-line treatment, ketamine requires careful supervision by specialists to ensure safe and effective use within a structured care framework.
Abstract
Ketamine, an anaesthetic and sedative drug, has emerged as a promising therapeutic option for the management of chronic refractory pain, but is used off-label in this indication and known for its psychomimetic side-effects. The primary objective of this manuscript is to synthesize the current evidence on ketamine efficacy and safety for chronic refractory pain. Furthermore, it aims to identify critical knowledge gaps and propose a framework for its rational and safe clinical application. This narrative review analyses key findings from randomised and non-randomised clinical trials investigating ketamine's use in chronic pain conditions. It also examines existing clinical guidelines and expert consensus statements to reach a comprehensive clinical perspective. Current evidence demonstrates that ketamine can provide significant short-term analgesia, especially in neuropathic pain, and is fairly well-tolerated in patients with severe refractory pain. However, long-term data on efficacy, cognitive impact, addiction risk and optimal dosing are severely lacking. The intravenous route remains the most studied, while alternatives are still underexplored. Ketamine is not a first-line treatment for pain and must be prescribed and supervised by trained specialists within a structured standard of care. Its future role in pain management hinges on collaborative translational research to define optimal administration routes, establish phenotyping strategies (on the basis of pain type, comorbidities and comedication), and conduct long-term studies assessing mood, quality of life and cognitive function to ensure both efficacy and safety.