Rational pain management in complex regional pain syndrome 1 (CRPS 1)--a network meta-analysis

Pain Med. 2014 Sep;15(9):1575-89. doi: 10.1111/pme.12466.


Objective: Guidelines for complex regional pain syndrome (CRPS) 1 advocate several substance classes to reduce pain and support physical rehabilitation, but guidance about which agent should be prioritized when designing a therapeutic regimen is not provided. Using a network meta-analytic approach, we examined the efficacy of all agent classes investigated in randomized clinical trials of CRPS 1 and provide a rank order of various substances stratified by length of illness duration.

Design: In this study a network meta-analysis was conducted.

Patients: The participants of this study were patients with CRPS 1.

Method: Searches in electronic, previous systematic reviews, conference abstracts, book chapters, and the reference lists of relevant articles were performed. Eligible studies were randomized controlled trials comparing at least one analgesic agent with placebo or with another analgesic and reporting efficacy in reducing pain. Summary efficacy stratified by symptom duration and length of follow-up was computed across all substance classes. Two authors independently extracted data.

Results: In total, 16 studies were included in the analysis. Bisphosphonates appear to be the treatment of choice in early stages of CRPS 1. The effects of calcitonin surpass that of bisphosphonates and other substances as a short-term medication in more chronic stages of the illness. While most medications showed some efficacy on short-term follow-up, only bisphosphonates, NMDA analogs, and vasodilators showed better long-term pain reduction than placebo.

Limitation: For some drug classes, only a few studies were available and many studies included a small group of patients. Insufficient data were available to analyze efficacy on disability.

Conclusion: This network meta-analysis indicates that a rational pharmacological treatment strategy of pain management should consider bisphosphonates in early CRPS 1 and a short-term course of calcitonin in later stages. While most medications showed some efficacy on short-term follow-up, only bisphosphonates, NMDA analogs and vasodilators showed better long-term pain reduction than placebo.

Keywords: CRPS; Complex Regional Pain Syndrome; Network Meta-Analysis; Pain Management; Treatment Strategy.

Publication types

  • Meta-Analysis

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Aged
  • Amines / therapeutic use
  • Analgesics / classification
  • Analgesics / therapeutic use*
  • Cyclohexanecarboxylic Acids / therapeutic use
  • Diphosphonates / therapeutic use
  • Drug Utilization / statistics & numerical data
  • Follow-Up Studies
  • Gabapentin
  • Humans
  • Ketamine / therapeutic use
  • Middle Aged
  • N-Methylaspartate / agonists
  • Pain Management*
  • Practice Guidelines as Topic
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • Reflex Sympathetic Dystrophy / drug therapy*
  • Treatment Outcome
  • Vasodilator Agents / therapeutic use
  • gamma-Aminobutyric Acid / therapeutic use


  • Adrenal Cortex Hormones
  • Amines
  • Analgesics
  • Cyclohexanecarboxylic Acids
  • Diphosphonates
  • Vasodilator Agents
  • gamma-Aminobutyric Acid
  • N-Methylaspartate
  • Ketamine
  • Gabapentin