Efficacy and Safety of Pharmacological Treatment in Patients with Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis.

A systematic review and meta-analysis of 23 randomized controlled trials involving 1029 patients with complex regional pain syndrome found that bisphosphonates and ketamine each provide long-term (beyond one month) pain relief, though neither showed statistically significant short-term benefit. Both treatments caused mild adverse events that required no special intervention. Ketamine and bisphosphonates appeared to be the best pharmacological strategies for pain relief in CRPS.

Study at a glance

Abstract

Complex regional pain syndrome (CRPS) is a disabling condition that usually affects the extremities after trauma or surgery. At present, there is no FDA-approved pharmacological treatment for patients with CRPS. We performed this systematic review and meta-analysis to evaluate the efficacy and safety of pharmacological therapies and determine the best strategy for CRPS. We searched the databases, including PubMed, Embase, Cochrane, Web of Science, Scopus, and ClinicalTrials.gov, for published eligible randomized controlled trials (RCTs) comparing pharmacological treatment with placebo in CRPS patients. Target patients were diagnosed with CRPS according to Budapest Criteria in 2012 or the 1994 consensus-based IASP CRPS criteria. Finally, 23 RCTs comprising 1029 patients were included. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to rate certainty (confidence in evidence and quality of evidence). Direct meta-analysis showed that using bisphosphonates (BPs) (mean difference [MD] -2.21, 95% CI -4.36--0.06, p = 0.04, moderate certainty) or ketamine (mean difference [MD] -0.78, 95% CI -1.51--0.05, p = 0.04, low certainty) could provide long-term (beyond one month) pain relief. However, there was no statistically significant difference in the efficacy of short-term pain relief. Ketamine (rank p = 0.55) and BPs (rank p = 0.61) appeared to be the best strategies for CRPS pain relief. Additionally, BPs (risk ratio [RR] = 1.86, 95% CI 1.34-2.57, p < 0.01, moderate certainty) and ketamine (risk ratio [RR] = 3.45, 95% CI 1.79-6.65, p < 0.01, moderate certainty) caused more adverse events, which were mild, and no special intervention was required. In summary, among pharmacological interventions, ketamine and bisphosphonate injection seemed to be the best treatment for CRPS without severe adverse events.