Mesotherapy With Lidocaine and Ketamine in Complex Regional Pain Syndrome Type 1: A Randomized Double‐Blind Trial

ABSTRACT Background Complex regional pain syndrome type 1 (CRPS1) is a disabling pain syndrome whose treatment remains challenging. Mesotherapy is a therapeutic method involving the injection of low doses of active substances through the skin. No studies assessed mesotherapy in CRPS1 patients. The aim of this study was to evaluate the efficacy on pain relief of ketamine and lidocaine mixtures versus lidocaine alone administered by mesotherapy. Methods This three‐arm, randomized, double‐blind trial compared mesotherapy with lidocaine 20 mg alone or mixed with ketamine at a dose of 20 mg or 40 mg, in addition to standard treatment. The primary outcome was the difference in pain between inclusion and D56 after four mesotherapy sessions, assessed by a visual analog scale (VAS). Results Thirty‐one patients were randomized to receive lidocaine 20 mg ( n = 10), lidocaine 20 mg + ketamine 20 mg ( n = 11), or lidocaine 20 mg + ketamine 40 mg ( n = 10). The mean difference in VAS score between inclusion and D56 was −25.60 (95% CI: −42.81, −8.39) in the lidocaine 20 mg group, −10.13 (95% CI: −26.24, 5.99) in the lidocaine 20 mg + ketamine 20 mg group, and −19.06 (95% CI: −36.11, −2.02) in the lidocaine 20 mg + ketamine 40 mg group. There was no statistically significant difference in change of VAS score between the 3 groups ( p = 0.36). No infectious or severe adverse events occurred. Conclusion This study did not demonstrate the superiority of mesotherapy with ketamine and lidocaine mixtures compared to lidocaine alone in relieving pain for CRPS1 patients. Lidocaine alone or mixed with ketamine can be administered safely with a rigorous mesotherapy procedure. Trial Registration: The study was registered with ClinicalTrials.gov , number NCT04650074, and EudraCT, number 2020‐005557‐24