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

Complex regional pain syndrome (CRPS) is characterised by 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 such as swelling, discolouration, stiffness, weakness and changes to the skin. This overview sought to summarise and report all of the available evidence arising from systematic reviews for all treatments for this condition regarding how well they work and any potential harm that they might cause.

We identified six Cochrane reviews and 13 non-Cochrane systematic reviews that included evidence relating to a broad range of treatments, from drugs to surgical procedures, rehabilitation and alternative therapies. For most treatments there were only a small number of published trials and the quality of these trials was mixed. As such, most of the evidence for most treatments is of low or very low quality and can not be regarded as reliable.

We found low quality evidence that a daily course of the drug ketamine delivered intravenously may effectively reduce pain, although it is also associated with a variety of side effects. We found low quality evidence that the bisphosphonate class of drugs, calcitonin and programmes of graded motor imagery may be effective for CRPS, and that mirror therapy may be effective in people who develop CRPS after suffering a stroke. Low quality evidence suggested that physiotherapy and occupational therapy did not lead to clinically important benefits at one year follow up, and that blocking sympathetic nerves with local anaesthetic is not effective. There is moderate quality evidence that an intravenous regional blockade using the drug guanethidine is not effective and may be associated with complications.

For a range of other interventions we found only very low quality evidence or no evidence at all. No conclusions should be drawn regarding the value of these interventions based on this level of evidence.

Based on the existing evidence it is difficult to draw firm conclusions as to which therapies should be offered to patients with CRPS. Better quality research is vital to reduce uncertainty in this area and is necessary before confident recommendations can be made.

Authors' conclusions: 

There is a critical lack of high quality evidence for the effectiveness of most therapies for CRPS. Until further larger trials are undertaken, formulating an evidence-based approach to managing CRPS will remain difficult.

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There is currently no strong consensus regarding the optimal management of complex regional pain syndrome although a multitude of interventions have been described and are commonly used.


To summarise the evidence from Cochrane and non-Cochrane systematic reviews of the effectiveness of any therapeutic intervention used to reduce pain, disability or both in adults with complex regional pain syndrome (CRPS).


We identified Cochrane reviews and non-Cochrane reviews through a systematic search of the following databases: Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects (DARE), Ovid MEDLINE, Ovid EMBASE, CINAHL, LILACS and PEDro. We included non-Cochrane systematic reviews where they contained evidence not covered by identified Cochrane reviews. The methodological quality of reviews was assessed using the AMSTAR tool.

We extracted data for the primary outcomes pain, disability and adverse events, and the secondary outcomes of quality of life, emotional well being and participants' ratings of satisfaction or improvement. Only evidence arising from randomised controlled trials was considered. We used the GRADE system to assess the quality of evidence.

Main results: 

We included six Cochrane reviews and 13 non-Cochrane systematic reviews. Cochrane reviews demonstrated better methodological quality than non-Cochrane reviews. Trials were typically small and the quality variable.

There is moderate quality evidence that intravenous regional blockade with guanethidine is not effective in CRPS and that the procedure appears to be associated with the risk of significant adverse events.

There is low quality evidence that bisphosphonates, calcitonin or a daily course of intravenous ketamine may be effective for pain when compared with placebo; graded motor imagery may be effective for pain and function when compared with usual care; and that mirror therapy may be effective for pain in post-stroke CRPS compared with a 'covered mirror' control. This evidence should be interpreted with caution. There is low quality evidence that local anaesthetic sympathetic blockade is not effective. Low quality evidence suggests that physiotherapy or occupational therapy are associated with small positive effects that are unlikely to be clinically important at one year follow up when compared with a social work passive attention control.

For a wide range of other interventions, there is either no evidence or very low quality evidence available from which no conclusions should be drawn.