Pharmacological treatment in adult patients with CRPS-I: a systematic review and meta-analysis of randomized controlled trials

Abstract

Abstract Objective Several pharmacological treatments have been proposed for the treatment of complex regional pain syndrome type-I (CRPS-I) in adults, but data regarding the efficacy of various agents for this disease is scarce. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to analyse the efficacy of the various pharmacological approaches in adults with CRPS-I. Methods We systematically searched PubMed, Scopus, and Web of Science databases from the inception date to 30 June 2021 to identify placebo-controlled or active-controlled RCTs using bisphosphonates, ketamine, CSs, anti-epileptics, NSAIDs/COXIBs, opiates, antidepressants, scavengers/magnesium sulphate or IVIGs for the treatment of CRPS-I. The primary outcomes included changes in the visual analogue scale (VAS) or numeric rating scale (NRS) for pain before and after treatment. Results We included 20 placebo-controlled or active-controlled RCTs (including a total of 818 adults with CRPS-I) that used bisphosphonates (n = 7), ketamine (n = 2), CSs (n = 2), anti-epileptics (n = 1), NSAIDs/selective inhibitors of cyclooxygenase-2 (COXIBs) (n = 2), scavengers/magnesium sulphate (n = 5), or IVIGs (n = 1) to treat CRPS-I during a median follow-up of 26 weeks. Treatment with bisphosphonates showed a significant reduction in the values of the VAS/NRS pain scale compared with placebo or reference therapy (random effects weighted mean difference [WMD]: −23.8, 95% CI: −28.0 to −19.6; I2 = 36.4%). Treatment with ketamine also documented a reduction in the values of the VAS/NRS for pain (random effects WMD: −8.27, 95% CI: −12.9 to −3.70; I2 = 0%). Treatment with other agents did not reduce the values of the VAS/NRS assessments of pain. Conclusion This systematic review and meta-analysis supports the recommendation of parenteral bisphosphonates as the first-line agent in the treatment of CRPS-I. Trial registration Open Science Framework registries, https://osf.io/et9gu/, osf.io/et9gu.