Physical Medicine and Rehabilitation for Complex Regional Pain Syndromes Medication

Updated: Feb 06, 2019
  • Author: Manish K Singh, MD; Chief Editor: Stephen Kishner, MD, MHA  more...
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Medication Summary

Multiple classes of medications have been tried for patients with CRPS, often with variable results and generally with limited published research to help clinicians predict which patients will respond well to a particular medication. [33]

Analgesic drug therapy for CRPS can be divided into the following categories:

Opioid analgesics

  • Opioids are used commonly as an analgesic for many pain syndromes.

  • Opioid therapy can be a safe and good option in patients with intractable nonmalignant pain and no history of drug abuse.

  • Quang-Cantagrel and colleagues reported that failure of one opioid cannot predict the patient's response to another opioid. [34]

  • High doses of tramadol may provide effective and safe relief in neuropathic pain, including allodynia.

Nonopioid analgesics (eg, NSAIDs, acetaminophen)

  • Acetaminophen is a safe choice for treatment of pain during pregnancy and breastfeeding.

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) are discussed in further detail within the tables below.


Antidepressant medications play a major role in treatment of neuropathic pain.

  • Tricyclic antidepressants:

    • Amitriptyline (Elavil)

    • Imipramine (Tofranil)

    • Doxepin (Sinequan)

    • Clomipramine (Anafranil)

    • Nortriptyline (Pamelor)

  • Selective serotonin reuptake inhibitor (SSRI) antidepressants:

    • Paroxetine (Paxil)

    • Fluoxetine (Prozac)

    • Sertraline (Zoloft)

    • Escitalopram (Lexapro)

  • Other antidepressants:

    • Nefazodone (Serzone)

    • Venlafaxine (Effexor)

    • Duloxetine (Cymbalta)

    • Bupropion (Wellbutrin)


  • Sodium channel antagonists have been used in the management of neuropathic pain for several years.

  • These medications are started slowly and are administered as needed.

  • The patient is monitored carefully.

  • Use of several anticonvulsant drugs (eg, pregabalin, carbamazepine, phenytoin, sodium valproate, clonazepam, topiramate, lamotrigine) has been tried in the treatment of RSD.

  • In studies by Nicholson and by Rowbothan and colleagues, gabapentin has been reported to be effective in the management of chronic neuropathic pain syndromes. [35]

  • Controlled studies for the effect of lamotrigine have not become available yet, but Jain notes that the drug has shown effect in neuropathic pain.

  • Ziconotide may be useful in the future for neuropathic pain, as Jain notes that it has a favorable risk/benefit ratio, with advantages over several currently available intrathecal therapies for pain. [36]

Other adjunct analgesics

  • Hewitt states that N -methyl-D-aspartate (NMDA) – receptor antagonists, including ketamine and dextromethorphan, may have potential as co-analgesics when used in combination with opioids. Some studies have shown that ketamine infusion therapy provides effective pain relief and does not have adverse cognitive effects with extended use. [37, 38]

  • Benzodiazepines, baclofen, and tizanidine may be helpful in decreasing spasm and providing pain relief.

  • Corticosteroid, mexiletine (orally active class Ib anti-arrhythmic agent), nifedipine (calcium channel blocker), propranolol (beta blocker), phenoxybenzamine (alpha blocker), and clonidine (alpha2-adrenergic agonist) are other alternatives. Some drug trials provided consistent support for analgesia with corticosteroids in the early stage and may have long-term effectiveness.

  • Lidoderm 5% patches are sometimes helpful in decreasing allodynia and providing pain relief.

  • Although it has not been approved by the Food and Drug Administration (FDA) for this indication, botulinum toxin can be considered for dystonia seen in patients with RSD.


Nonsteroidal anti-inflammatory drugs

Class Summary

These inhibit inflammatory reactions and pain by decreasing activity of cyclo-oxygenase, which is responsible for prostaglandin synthesis. NSAIDs may provide pain relief in the early stage of RSD.

Ibuprofen (Motrin, Advil)

NSAIDs are used commonly for patients with mild to moderate pain. Inhibit inflammatory reactions and pain by decreasing prostaglandin synthesis.

Naproxen sodium (Anaprox, Naprelan, Naprosyn)

For relief of mild to moderate pain; inhibits inflammatory reactions and pain by decreasing activity of cyclo-oxygenase, which results in a decrease of prostaglandin synthesis.



Class Summary

These drugs increase the synaptic concentration of serotonin and/or norepinephrine in the CNS by inhibiting their re-uptake by the presynaptic neuronal membrane. Similar agents that can be helpful are duloxetine (Cymbalta) and venlafaxine (Effexor).

Nortriptyline (Pamelor)

Has demonstrated effectiveness in the treatment of chronic and neuropathic pain.

Amitriptyline (Elavil)

Has demonstrated effectiveness in certain chronic and neuropathic pain.

Duloxetine (Cymbalta)

Indicated for diabetic peripheral neuropathic pain. Potent inhibitor of neuronal serotonin and norepinephrine reuptake.



Class Summary

Use of certain anti-epileptic drugs, such as the GABA analogue gabapentin (Neurontin), has proven helpful in some cases of neuropathic pain. Other anticonvulsant drugs (eg, carbamazepine, phenytoin, sodium valproate or clonazepam, topiramate, lamotrigine, zonisamide, tiagabine) also have been tried in RSD.

Gabapentin (Neurontin)

Has anticonvulsant properties and antineuralgic effects; however, exact mechanism of action is unknown. Structurally related to GABA but does not interact with GABA receptors.

Pregabalin (Lyrica)

Structural derivative of GABA. Mechanism of action unknown. Binds with high affinity to alpha 2 -delta site (a calcium channel subunit). In vitro, reduces calcium-dependent release of several neurotransmitters, possibly by modulating calcium channel function. FDA approved for neuropathic pain associated with diabetic peripheral neuropathy or postherpetic neuralgia and as adjunctive therapy in partial-onset seizures.


Opioid analgesics

Class Summary

These commonly used analgesics are employed for many pain syndromes.

Oxycodone (OxyContin)

Currently, the long-acting form of opioids is commonly used in initial and later stages of RSD. Start with a small dose and increase gradually.

Morphine sulfate (MS Contin, Avinza, Kadian, Duramorph, Astramorph)

DOC for analgesia due to reliable and predictable effects, safety profile, and ease of reversibility with naloxone. Various IV doses are used; commonly titrated until desired effect obtained.

Fentanyl transdermal patch (Duragesic)

Potent narcotic analgesic with much shorter half-life than morphine sulfate. Excellent choice for pain management and sedation with short duration (30-60 min) and easy to titrate. Easily and quickly reversed by naloxone.

When using transdermal dosage form, most patients are controlled with 72 h dosing intervals; however, some patients may require dosing intervals of 48 h.