Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

early CRPS (within 6 months of onset)

1st line – physical and occupational therapy

Back
ONGOING
|
early CRPS (within 6 months of onset)
1st line – 

physical and occupational therapy

The main goal of treatment is to reduce pain and increase limb function and mobility. Improvement in associated abnormalities will follow if treatment is successful.

The aims of physical therapy are to reduce edema, decrease muscle guarding, and improve function in daily activities. This may involve bandaging, desensitization techniques, and active and passive movement exercises.

Stress loading encourages active movement and should be encouraged as early as possible.

Functional therapy concentrates on improving the range of motion and functional dexterity required for activities of daily living.[57] The time frame is extremely varied, and the patient may require intensive sessions 3-5 times a week initially.

Graded motor imagery (GMI) and mirror visual feedback (MFV) therapy consist of phased limb laterality recognition, imagined movement, and mirror movement phases over a period of time. GMI and MFV therapy reduced pain and increased movement in the affected limb in small numbers of patients, mostly those with upper limb involvement.[52]​​[56]​​ Although the mechanisms behind this therapy are unknown and the quality of the evidence is low, further investigation is warranted.[56]​​[59][60]

Plus – psychological therapies

Back
ONGOING
|
early CRPS (within 6 months of onset)
Plus – 

psychological therapies

Treatment recommended for ALL patients in selected patient group

Studies have suggested that patients with CRPS do not differ psychologically from other patients with chronic pain.[61] There is evidence that standard psychological therapies may be useful as part of a comprehensive interdisciplinary treatment program.​​​[16][52][61]

Psychosocial and behavioral management play an important role in a holistic multimodal approach to the management of CRPS. The goals are to identify psychological factors perpetuating pain and disability, treat anxiety and depression, and facilitate an environment to reduce barriers and promote healthy functioning.[16][36][62]

Consider – prednisone

Back
ONGOING
|
early CRPS (within 6 months of onset)
Consider – 

prednisone

Treatment recommended for SOME patients in selected patient group

A short course of oral prednisone may be offered in the early stages of CRPS, with the aim of decreasing inflammation in the affected limb.[52][63]

Relative contraindications include diabetes, osteoporosis, glaucoma, cataracts, peptic ulcers, and hypertension.

Reduced doses and length of treatment might be reasonably trialed to assess symptom response. One trial used 40 mg/day of oral prednisone tapered down by 5 mg/day at weekly intervals.[97]

Primary options

prednisone: consult specialist for guidance on dose

Consider – nonsteroidal anti-inflammatory drug (NSAID)

Back
ONGOING
|
early CRPS (within 6 months of onset)
Consider – 

nonsteroidal anti-inflammatory drug (NSAID)

Treatment recommended for SOME patients in selected patient group

NSAIDs are often used as first-line treatment for CRPS, especially at initial presentation. However, they remain poorly studied specifically for CRPS, with no guidance on choice of NSAID therapy. Most guidelines recommend moderate to higher doses for 2-4 weeks, at which time response of medication can be assessed. Long-term use at these doses is generally not advised. There are no specific data for selective cyclo-oxygenase-2 (COX-2) inhibitors as an alternative option for CRPS.[52]​​[63]

Examples of NSAIDs are included here (at licensed doses), but there are numerous NSAIDs available and you should consult your local protocols.

Primary options

ibuprofen: 300-800 mg orally every 6-8 hours when required, maximum 3200 mg/day

OR

diclofenac potassium: 50 mg orally (immediate-release) three times daily when required

Consider – bisphosphonate

Back
ONGOING
|
early CRPS (within 6 months of onset)
Consider – 

bisphosphonate

Treatment recommended for SOME patients in selected patient group

Bisphosphonates have shown promise in several randomized controlled trials in patients with evidence of osteopenia or osteoporosis in the affected limb.[52][63][67] ​ Both oral and intravenous therapy has been tried, and there is no evidence for superiority of a particular regimen.

Potential (rare) adverse effects of long-term use of bisphosphonates include jaw necrosis and atypical femur fractures.[68]

Primary options

alendronate: 10 mg orally once daily

OR

pamidronate: 60 mg intravenously as a single dose

Consider – antidepressant

Back
ONGOING
|
early CRPS (within 6 months of onset)
Consider – 

antidepressant

Treatment recommended for SOME patients in selected patient group

Tricyclic antidepressants are effective in several neuropathic pain states.[52]​ Amitriptyline is the most widely tested, but nortriptyline and desipramine may be more effective due to their more selective noradrenergic activity, and nortriptyline has fewer adverse effects.

For patients who do not tolerate or respond to, or are not candidates for, tricyclic antidepressants, the use of serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine, venlafaxine, or desvenlafaxine may be considered (similar to other neuropathic pain states), although there are no specific studies for CRPS.[52]​​

Primary options

nortriptyline: 10-25 mg orally once daily, increase by 10-25 mg/day increments at weekly intervals according to response, maximum 100 mg/day

OR

desipramine: 10-25 mg orally once daily, increase by 10-25 mg/day increments at weekly intervals according to response, maximum 100 mg/day

OR

amitriptyline: 10-25 mg orally once daily, increase by 10-25 mg/day increments at weekly intervals according to response, maximum 100 mg/day

OR

duloxetine: 30-60 mg orally once daily

Secondary options

venlafaxine: 75-225 mg orally (extended-release) once daily

OR

desvenlafaxine: 50-200 mg orally once daily

Consider – anticonvulsant

Back
ONGOING
|
early CRPS (within 6 months of onset)
Consider – 

anticonvulsant

Treatment recommended for SOME patients in selected patient group

Anticonvulsants are of benefit in neuropathic pain and have been used with some success in the treatment of CRPS.

Gabapentin is the most widely tested and used; pregabalin may be better tolerated, but its effectiveness has not been studied in randomized controlled trials.[52]​​

Topiramate, lamotrigine, or levetiracetam may be tried if gabapentin or pregabalin are ineffective or not tolerated.[52]​​

Primary options

gabapentin: 300 mg orally once daily initially, increase according to response, maximum 3600 mg/day

OR

pregabalin: 100 mg orally twice daily initially, increase according to response, maximum 600 mg/day

Secondary options

topiramate: 50 mg orally once daily initially, increase according to response, maximum 400 mg/day

OR

lamotrigine: consult specialist for guidance on dose

OR

levetiracetam: 500 mg orally twice daily initially, increase according to response, maximum 3000 mg/day

Consider – alpha antagonist or agonist

Back
ONGOING
|
early CRPS (within 6 months of onset)
Consider – 

alpha antagonist or agonist

Treatment recommended for SOME patients in selected patient group

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.[52]​​[55][69]​ However, evidence is based on case series, and the alpha-adrenergic antagonist is often used in combination with other neuropathic agents such as anticonvulsants or antidepressants.[52]​​

Primary options

prazosin: consult specialist for guidance on dose

OR

phenoxybenzamine: consult specialist for guidance on dose

OR

clonidine: consult specialist for guidance on dose

Consider – topical local anesthetic

Back
ONGOING
|
early CRPS (within 6 months of onset)
Consider – 

topical local anesthetic

Treatment recommended for SOME patients in selected patient group

Topical anesthetics in the form of patches containing lidocaine, or creams containing lidocaine alone or with prilocaine, can be applied to affected areas.[52]​​

The patches can be used for 12 out of every 24 hours and up to three patches at one time.

The creams are best applied under plastic wrap using gloves.

May be used in combination with other pharmacologic therapies.

Primary options

lidocaine topical patch: (5%) apply up to 3 patches to affected area(s) for a maximum of 12 hours/day

OR

lidocaine topical cream: (3%) apply to the affected area(s) two to three times daily when required

Secondary options

lidocaine/prilocaine topical: (2.5%/2.5%) apply 2.5 g to the affected area(s), maximum 4 hours exposure

Consider – transcutaneous electrical nerve stimulation (TENS)

Back
ONGOING
|
early CRPS (within 6 months of onset)
Consider – 

transcutaneous electrical nerve stimulation (TENS)

Treatment recommended for SOME patients in selected patient group

Although formal evidence for the effectiveness of TENS is lacking, clinical experience suggests a beneficial effect for some CRPS patients.[78][79] At the start of TENS treatment, pain may increase for a few seconds to minutes, followed by a more prolonged decrease with continued use. TENS is safe to use in combination with pharmacologic therapies.

Consider – sympathetic nerve block

Back
ONGOING
|
early CRPS (within 6 months of onset)
Consider – 

sympathetic nerve block

Treatment recommended for SOME patients in selected patient group

Controversial. There are significant concerns regarding the exact role of the sympathetic nervous system in CRPS, the indications for blocking sympathetic nerves, efficacy, lack of sufficient randomized controlled trials, placebo effect, and risk potential.[46][80][81][82][83]​​

Local anesthetic injection into the stellate ganglion or lumbar sympathetic ganglion may allow short-term clinical improvement in some patients, permitting more active physical therapy during that period.[47] If a diagnostic sympathetic block is successful, a series of 3-6 blocks may be administered to promote physical therapy.

chronic CRPS (>6 months since onset)

1st line – physical and occupational therapy

Back
ONGOING
|
chronic CRPS (>6 months since onset)
1st line – 

physical and occupational therapy

The main goal of treatment is to reduce pain and increase limb function and mobility. Improvement in associated abnormalities will follow if pain reduction and increased mobility are successful.

The aims of physical therapy are to reduce edema, decrease muscle guarding, and improve function in daily activities. This may involve bandaging, desensitization techniques, and active and passive movement exercises.

Stress loading encourages active movement and should be encouraged as early as possible.

Functional therapy concentrates on improving the range of motion and functional dexterity required for activities of daily living.[57] The time frame is extremely varied, and the patient may require intensive sessions 3-5 times a week initially.

Graded motor imagery (GMI) and mirror visual feedback (MFV) therapy consist of phased limb laterality recognition, imagined movement, and mirror movement phases over a period of time. GMI and MFV therapy reduced pain and increased movement in the affected limb in small numbers of patients, mostly those with upper limb involvement.[52]​​[56]​ Although the mechanisms behind this therapy are unknown and the quality of the evidence is low, further investigation is warranted.[56]​​[59][60]

Plus – psychological therapies

Back
ONGOING
|
chronic CRPS (>6 months since onset)
Plus – 

psychological therapies

Treatment recommended for ALL patients in selected patient group

Studies have suggested that patients with CRPS do not differ psychologically from other patients with chronic pain.[61] There is evidence that standard psychological therapies may be useful as part of a comprehensive interdisciplinary treatment program.[16][52][61]

Psychosocial and behavioral management play an important role in a holistic multimodal approach to the management of CRPS. The goals are to identify psychological factors perpetuating pain and disability, treat anxiety and depression, and facilitate an environment to reduce barriers and promote healthy functioning.[16][36][62]

Consider – antidepressant

Back
ONGOING
|
chronic CRPS (>6 months since onset)
Consider – 

antidepressant

Treatment recommended for SOME patients in selected patient group

Tricyclic antidepressants are effective in several neuropathic pain states.[52]​ Amitriptyline is the most widely tested, but nortriptyline and desipramine may be more effective due to their more selective noradrenergic activity, and nortriptyline has fewer adverse effects

For patients who do not tolerate or respond to, or are not candidates for, tricyclic antidepressants, the use of serotonin-norepinephrine reuptake inhibitors (SNRIs) such as duloxetine, venlafaxine, or desvenlafaxine may be considered (similar to other neuropathic pain states), although there are no specific studies for CRPS.[52]​​

Primary options

nortriptyline: 10-25 mg orally once daily, increase by 10-25 mg/day increments at weekly intervals according to response, maximum 100 mg/day

OR

desipramine: 10-25 mg orally once daily, increase by 10-25 mg/day increments at weekly intervals according to response, maximum 100 mg/day

OR

amitriptyline: 10-25 mg orally once daily, increase by 10-25 mg/day increments at weekly intervals according to response, maximum 100 mg/day

OR

duloxetine: 30-60 mg orally once daily

Secondary options

venlafaxine: 75-225 mg orally (extended-release) once daily

OR

desvenlafaxine: 50-200 mg orally once daily

Consider – anticonvulsant

Back
ONGOING
|
chronic CRPS (>6 months since onset)
Consider – 

anticonvulsant

Treatment recommended for SOME patients in selected patient group

Anticonvulsants are of benefit in neuropathic pain and have been used with some success in the treatment of CRPS.

Gabapentin is the most widely tested and used; pregabalin may be better tolerated, but its effectiveness has not been studied in randomized controlled trials.[52]​​

Topiramate, lamotrigine, or levetiracetam may be tried if gabapentin or pregabalin are ineffective or not tolerated.

Primary options

gabapentin: 300 mg orally once daily initially, increase according to response, maximum 3600 mg/day

OR

pregabalin: 100 mg orally twice daily initially, increase according to response, maximum 600 mg/day

Secondary options

topiramate: 50 mg orally once daily initially, increase according to response, maximum 400 mg/day

OR

lamotrigine: consult specialist for guidance on dose

OR

levetiracetam: 500 mg orally twice daily initially, increase according to response, maximum 3000 mg/day

Consider – topical local anesthetic

Back
ONGOING
|
chronic CRPS (>6 months since onset)
Consider – 

topical local anesthetic

Treatment recommended for SOME patients in selected patient group

Topical anesthetics in the form of patches containing lidocaine, or creams containing lidocaine alone or with prilocaine, can be applied to affected areas.[52]​​

The patches can be used for 12 out of every 24 hours and up to three patches at one time.

The creams are best applied under plastic wrap using gloves.

May be used in combination with other pharmacologic therapies.

Primary options

lidocaine topical patch: (5%) apply up to 3 patches to affected area(s) for a maximum of 12 hours/day

OR

lidocaine topical cream: (3%) apply to the affected area(s) two to three times daily when required

Secondary options

lidocaine/prilocaine topical: (2.5%/2.5%) apply 2.5 g to the affected area(s), maximum 4 hours exposure

Consider – transcutaneous electrical nerve stimulation (TENS)

Back
ONGOING
|
chronic CRPS (>6 months since onset)
Consider – 

transcutaneous electrical nerve stimulation (TENS)

Treatment recommended for SOME patients in selected patient group

Although formal evidence for the effectiveness of TENS is lacking, clinical experience suggests a beneficial effect for some CRPS patients.[78][79]​​ At the start of TENS treatment, pain may increase for a few seconds to minutes, followed by a more prolonged decrease with continued use. TENS is safe to use in combination with pharmacologic therapies.

Consider – opioid

Back
ONGOING
|
chronic CRPS (>6 months since onset)
Consider – 

opioid

Treatment recommended for SOME patients in selected patient group

The use of opioid analgesics in neuropathic pain states, including CRPS, is controversial. Dependency behavior is a risk, and mortality has been demonstrated with persistent use of strong opioids, with a dose-dependent relationship. Opioids should only be considered once other options have been tried, and if the expected benefits are anticipated to outweigh risks to the patient.[70]

Tramadol, methadone, oxycodone, and transdermal fentanyl have been studied in neuropathic pain states. However, this does not necessarily indicate superiority over other opioids for treating refractory CRPS, and the choice of opioid and dosing should be made after careful consideration of patient comorbidities and risk factors.[52]​​[71]

2nd line – interventional and advanced therapies

Back
ONGOING
|
chronic CRPS (>6 months since onset)
2nd line – 

interventional and advanced therapies

Interventional and advanced therapies are usually reserved for the treatment of chronic CRPS when other treatments have failed to provide sufficient relief to allow physical therapy and functional rehabilitation.

A patient may continue with one or more pharmacologic analgesic therapies in addition to an interventional or advanced therapy.

Several methods are available, and their use depends on local practice and individual patient preference. If one approach is ineffective, another may be tried.

A sympathetic block may permit more active physical therapy.[47]

Nerve blocks with local anesthetic agents, clonidine, and opioids, either alone or in combination, as a single dose or continuous infusion, are commonly used with some success.[47] These can also be administered as an epidural infusion.

Peripheral nerve stimulation is indicated when symptoms are confined to one peripheral nerve distribution or respond to selective nerve blockade/regional block. However, newer PNS systems may allow stimulation of multiple peripheral nerves utilizing a single system.[89][90]

Spinal cord stimulation (SCS) may be considered for patients with diffuse symptoms (i.e., not confined to one anatomic region). If trial stimulation with temporary electrodes results in significant pain reduction and increased function over several days, permanent electrode placement is considered.[91] Clinical evidence from randomized controlled trials supports the use of SCS in the management of CRPS. It may be considered for patients with symptoms that are not confined to one anatomic region and in whom other treatments have not been effective. Possible complications include infection, nerve damage, lead migration and breakage, and implantable pulse generator site pain.[52][89][92][93][94][95]​​​​ SCS is usually reserved for patients who have not obtained relief with pharmacologic and less invasive interventional therapies.[52]​​[89]

Dorsal root ganglion (DRG) stimulation is another option, with some evidence that it may offer better outcomes than traditional SCS (dorsal column stimulation).[52]​​[89][96] 

Ketamine intravenous infusions have been used for the treatment of CRPS, with systematic reviews suggesting that subanesthetic doses may have low to moderate evidence of efficacy.[52][55][72][73][74] Ketamine is a potent N-methyl-D-aspartate (NMDA) antagonist, with potential mechanisms to alter and change neuronal plasticity and nociceptive signaling in the central nervous system at subanesthetic doses. Studies have not used a standardized dosing regimen, making comparing and interpreting the data difficult. Ketamine infusions may be used after failure of multimodal therapy, including interventional therapy, with careful consideration of patient comorbidities and risk for psychotomimetic and cardiac adverse effects, along with appropriate monitoring during and after treatment.[52]​​

Plus – continued physical and occupational therapy

Back
ONGOING
|
chronic CRPS (>6 months since onset)
Plus – 

continued physical and occupational therapy

Treatment recommended for ALL patients in selected patient group

The main goal of treatment is to reduce pain and increase limb function and mobility. Improvement in associated abnormalities will follow if pain reduction and increased mobility are successful.

The aims of physical therapy are to reduce edema, decrease muscle guarding, and improve function in daily activities. This may involve bandaging, desensitization techniques, and active and passive movement exercises.

Stress loading encourages active movement and should be encouraged as early as possible.

Functional therapy concentrates on improving the range of motion and functional dexterity required for activities of daily living.[57] The time frame is extremely varied and the patient may require intensive sessions 3-5 times a week initially.

Graded motor imagery (GMI) and mirror visual feedback (MFV) therapy consist of phased limb laterality recognition, imagined movement, and mirror movement phases over a period of time. GMI and MFV therapy reduced pain and increased movement in the affected limb in small numbers of patients, mostly those with upper limb involvement.[52]​​[56]​​ Although the mechanisms behind this therapy are unknown and the quality of the evidence is low, further investigation is warranted.[56]​​[59][60]

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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