Which treatments are effective for the management of complex regional pain syndrome in adults?

Key messages

There is a critical lack of high-quality evidence for the benefits and risks of most treatments for adults with complex regional pain syndrome (CRPS). Larger, well-designed studies and higher-quality reviews are needed to provide accurate evidence for benefits and risks of treatments for adults with CRPS.


What is complex regional pain syndrome?

CRPS is a disabling chronic pain condition. People with CRPS experience persistent pain, usually in the hands or feet, that is not proportionate in severity to any underlying injury. It often involves a variety of other symptoms in the affected body part such as swelling, discolouration, stiffness, weakness, and changes to skin quality. 


What did we want to find out?

A broad range of therapies are used to treat CRPS. The effects of these therapies are summarised across a number of Cochrane and non-Cochrane reviews. Our aim was to combine the information from these reviews into one accessible document. We specifically wanted to find out which treatments are effective in reducing pain and disability in adults with CRPS. We also wanted to find out whether these treatments cause any unwanted effects.


What did we do?

We searched for Cochrane and non-Cochrane reviews in the medical literature using online databases, from their beginning to October 2011, in the previous version of this overview, and between October 2011 and October 2022 in the current version. We included reviews that evaluated any treatment aiming to reduce pain intensity and disability in adults with CRPS. We judged the quality of the included reviews and summarised their results. We also rated our confidence in the evidence included in the reviews, based on factors such as study methods and size.


What did we find?

We included six Cochrane and 13 non-Cochrane systematic reviews in the previous version of this overview and five Cochrane and 12 non-Cochrane reviews in the current version. These reviews included evidence relating to a large range of treatments, including drugs, surgical procedures, rehabilitation, and complementary and alternative therapies. For most treatments, there were only a small number of published studies and the quality of these studies was low. The review evidence suggests the following:

     •   Compared with placebo (or 'dummy') treatment, bisphosphonates (a class of medicines that slow down bone loss) may reduce pain intensity shortly after treatment, but they are probably associated with some side effects.

   •   Compared with a placebo (or sham) treatment, blocking the branches of the sympathetic nervous system with an anaesthetic probably does not reduce pain intensity.

   •   There may not be any differences in the pain-reducing effects of a topical cream called dimethyl sulfoxide (DMSO) and an amino acid supplement called N-acetyl cysteine, but it is unclear whether either treatment works at all.

   •   One type of nerve block, called a brachial plexus block, may reduce pain intensity more than another type of block, called a bupivacaine stellate ganglion block.

For the majority of the commonly used drug, surgical, rehabilitation, and complementary and alternative therapies for CRPS, we found only very low-quality evidence or no evidence at all. As a result, we cannot be certain about their effects on pain and disability in CRPS.  

What are the limitations of the evidence?

All of the included non-Cochrane reviews were conducted in a way that affects the reliability of their findings. The studies included within both the Cochrane and non-Cochrane reviews had several limitations, particularly due to the small number of included participants. The results presented within this overview demonstrate unclear benefits and risks for most treatments for adults with CRPS.

How up-to-date is this evidence?

This overview updates our previous overview. The evidence is up-to-date to October 2022.

Authors' conclusions: 

Despite a considerable increase in included evidence compared with the previous version of this overview, we identified no high-certainty evidence for the effectiveness of any therapy for CRPS. Until larger, high-quality trials are undertaken, formulating an evidence-based approach to managing CRPS will remain difficult. Current non-Cochrane systematic reviews of interventions for CRPS are of low methodological quality and should not be relied upon to provide an accurate and comprehensive summary of the evidence.

Read the full abstract...

Complex regional pain syndrome (CRPS) is a chronic pain condition that usually occurs in a limb following trauma or surgery. It is characterised by persisting pain that is disproportionate in magnitude or duration to the typical course of pain after similar injury. There is currently no consensus regarding the optimal management of CRPS, although a broad range of interventions have been described and are commonly used. This is the first update of the original Cochrane review published in Issue 4, 2013.


To summarise the evidence from Cochrane and non-Cochrane systematic reviews of the efficacy, effectiveness, and safety of any intervention used to reduce pain, disability, or both, in adults with CRPS.


We identified Cochrane reviews and non-Cochrane reviews through a systematic search of Ovid MEDLINE, Ovid Embase, Cochrane Database of Systematic Reviews, CINAHL, PEDro, LILACS and Epistemonikos from inception to October 2022 , with no language restrictions. We included systematic reviews of randomised controlled trials that included adults (≥18 years) diagnosed with CRPS, using any diagnostic criteria. 

Two overview authors independently assessed eligibility, extracted data, and assessed the quality of the reviews and certainty of the evidence using the AMSTAR 2 and GRADE tools respectively. We extracted data for the primary outcomes pain, disability and adverse events, and the secondary outcomes quality of life, emotional well-being, and participants' ratings of satisfaction or improvement with treatment. 

Main results: 

We included six Cochrane and 13 non-Cochrane systematic reviews in the previous version of this overview and five Cochrane and 12 non-Cochrane reviews in the current version. Using the AMSTAR 2 tool, we judged Cochrane reviews to have higher methodological quality than non-Cochrane reviews. The studies in the included reviews were typically small and mostly at high risk of bias or of low methodological quality. We found no high-certainty evidence for any comparison. 

There was low-certainty evidence that bisphosphonates may reduce pain intensity post-intervention (standardised mean difference (SMD) -2.6, 95% confidence interval (CI) −1.8 to −3.4, P = 0.001; I2 = 81%; 4 trials, n = 181) and moderate-certainty evidence that they are probably associated with increased adverse events of any nature (risk ratio (RR) 2.10, 95% CI 1.27 to 3.47; number needed to treat for an additional harmful outcome (NNTH) 4.6, 95% CI 2.4 to 168.0; 4 trials, n = 181). 

There was moderate-certainty evidence that lidocaine local anaesthetic sympathetic blockade probably does not reduce pain intensity compared with placebo, and low-certainty evidence that it may not reduce pain intensity compared with ultrasound of the stellate ganglion. No effect size was reported for either comparison.

There was low-certainty evidence that topical dimethyl sulfoxide may not reduce pain intensity compared with oral N-acetylcysteine, but no effect size was reported.

There was low-certainty evidence that continuous bupivacaine brachial plexus block may reduce pain intensity compared with continuous bupivacaine stellate ganglion block, but no effect size was reported.

For a wide range of other commonly used interventions, the certainty in the evidence was very low and provides insufficient evidence to either support or refute their use. Comparisons with low- and very low-certainty evidence should be treated with substantial caution. We did not identify any RCT evidence for routinely used pharmacological interventions for CRPS such as tricyclic antidepressants or opioids.