Treatment

The treatment of complex regional pain syndrome is best commenced as soon as the diagnosis is made. Late treatment is associated with a poorer recovery but improvement in associated abnormalities will follow if pain reduction and increased mobility are successful.. Management is multi-modal and there are a variety of treatments which have been used in this condition. (1)

The Royal College of Physicians provides four 'pillars' of therapy: education, pain reduction, physical rehabilitation and attention to psychological needs, with the aim being to improve the quality of life. (2)

• Restoring function is pivotal.
• The key approach is a multidisciplinary one but should be centred around the GP and pain teams.
• Pain-related fear may be more disabling than pain itself.
• Ensure the patient's care does not become fragmented; they may end up seeing several different specialities.

Physiotherapy and rehabilitation is the cornerstone of treatment and should be considered in everyone, regardless of which speciality the patient is seeing when the initial diagnosis is made. Interventional approaches, such as repeated sympathetic nerve blocks, pharmacological therapy, and pain psychology may be utilised to facilitate patient participation in physiotherapy programmes. (3) Examples of physiotherapy options include:

• heat packs
• joint stretches
• muscle-strengthening exercises
• limb elevation
• compression wraps or gloves
• desensitisation regimens
• functional tasks
• biofeedback
• TENS
  

Despite this, the evidence for consistent benefit of physiotherapy for pain and disability in adults with complex regional pain syndrome is limited. (4)

Patient considerations and preferences should guide the choice of any drug therapy. There is currently no medication specifically licensed for CRPS.

Options include:

Simple analgesics. These are often first-line treatments (such as non-steroidal anti-inflammatory drugs) that are gradually increased in strength such that limb use can be encouraged with gentle exercise. There is no order of preference, and it may be necessary to try several agents in order to achieve pain relief. Most guidelines recommend moderate to higher doses for 2-4 weeks, at which time the patient response can be assessed. Long-term use at these doses is generally not advised. (3) Pain flares are normal but usually settle over a few days or weeks.

If pain is not reduced to a mild level by 3-4 weeks then neuropathic pain medication can be tried. Gabapentin is the most widely tested and used although pregabalin may be better tolerated. However, its effectiveness has not been studied in randomised controlled trials. (3)

Tricyclic antidepressants can be useful for the treatment of pain in early or late CRPS. For patients who do not tolerate or respond to, or are not candidates for, tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors (SNRIs) may be considered. (3)

The use of opioid analgesics in CRPS is controversial. Dependency is a significant risk, and mortality has been demonstrated with persistent use of strong opioids. These drugs should therefore only be considered once other options have been tried, and if the benefits are anticipated to outweigh the risks. (5)

Antidepressants may be needed if associated depression is present, and some patients with CRPS have evidence of active bone resorption which can be painful. Inhibiting bone resorption using bisphosphonates may reduce this. Both oral and intravenous therapy has been tried, but there is no evidence for superiority of a particular regimen.

Alpha-adrenergic antagonists and agonists, in particular alpha antagonists (e.g., prazosin, phenoxybenzamine) and alpha-2 agonists (e.g., clonidine), are possible treatments for sympathetically mediated pain in CRPS. (3)

Ketamine intravenous infusions have been used for the treatment of chronic CRPS, with systematic reviews suggesting that sub-anaesthetic doses may have low to moderate evidence of efficacy. (6) These may be used after failure of multi-modal therapy, with careful consideration of patient comorbidities and side effects, along with appropriate monitoring during and after treatment. (3)

Interventional therapies such as nerve blocks are usually reserved for the treatment of chronic CRPS when other treatments have failed. Several methods are available, and their use depends on local practice and individual patient preference.

Patients with CRPS should be followed up at regular intervals - frequently for the first 6 months, and less frequently once stable. Particular attention should be paid to response to therapy, any chronic changes, and mood disorders. (7)

References:

1. O'Connell NE, Wand BM, McAuley J, et al; Interventions for treating pain and disability in adults with complex regional pain syndrome. Cochrane Database Syst Rev. 2013 Apr 30;4
2. Complex regional pain syndrome in adults (2nd edition); Royal College of Physicians guideline (July 2018)
3. Harden RN, McCabe CS, Goebel A, et al. Complex regional pain syndrome: practical diagnostic and treatment guidelines, 5th Edition. Pain Med. 2022 Jun 10;23(suppl 1):S1-53.
4. Smart KM, Wand BM, O'Connell NE; Physiotherapy for pain and disability in adults with complex regional pain syndrome (CRPS) types I and II. Cochrane Database Syst Rev. 2016 Feb 24;2
5. Dowell D, Ragan KR, Jones CM, et al. CDC clinical practice guideline for prescribing opioids for pain - United States, 2022. MMWR Recomm Rep. 2022 Nov 4;71(3):1-95.
6. Cohen SP, Bhatia A, Buvanendran A, et al. Consensus guidelines on the use of intravenous ketamine infusions for chronic pain from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5): 521-46.
7. Goebel A, Barker C, Birklein F, et al. Standards for the diagnosis and management of complex regional pain syndrome: results of a European Pain Federation task force. Eur J Pain. 2019 Apr;23(4):641-51.