Treatment of Reflex Sympathetic Dystrophy

Drug Therapy for Reflex Sympathetic Dystrophy

Prompt initiation of medications for reflex sympathetic dystrophy (RSD) is very important, especially if the pain is intense, in order to enable the patient to proceed with physical therapy. During the course of treatment, medication doses may have to be adjusted to achieve optimal pain relief and to facilitate the patient's cooperation and participation in physical and occupational therapy. There is a shortage of information regarding effective pharmacotherapy for RSD due to limited numbers of randomized controlled trials. Most medications are prescribed based either on anecdotal evidence (patients have reported that a particular medication was effective for them) or based on studies that have shown that particular medications are effective for other neuropathic pain conditions such as peripheral neuropathy or trigeminal neuralgia.

There are no guidelines available regarding first-line medication for RSD. As a result, there is typically an initial trial-and-error period until the most effective medication is found. At that point, there may be a period of several adjustments until the correct dose is determined. Direct comparisons of the efficacy of drug therapy vs. other therapies such as physical therapy alone, nerve blocks, or spinal stimulation have not yet been investigated.

There are various classes of drugs that may be used for the treatment of RSD including:

• Analgesics
• Anticonvulsants
• Antidepressants
• Bisphosphonates
• Muscle relaxants
• Adrenergic active drugs
• Steroids
• Opioids

Analgesics (Pain Medications)

• Aspirin
• Acetaminophen
• Non-steroidal anti-inflammatory drugs (NSAIDs)

Side effects include:

• Nausea/vomiting
• Diarrhea
• Constipation
• Thinning of the blood (aspirin)

Anticonvulsants

A variety of anticonvulsants have been used in RSD patients to provide pain relief including: * Phenytoin (Dilantin) * Gabapentin (Neurontin) - this medication has been proven effective in clinical trials for neuropathic pain. Although there are no clinical trials showing efficacy for RSD, there is sufficient anecdotal evidence for pain relief that gabapentin is recommended by clinicians for treatment of RSD. * Carbamazepine (Tegretol)

Side effects of anticonvulsants include:

• Dizziness
• Drowsiness
• Nausea/vomiting
• Abnormalities of blood or platelet counts
• Abnormalities of liver function

Antidepressants

Tricyclic antidepressants may be very effective for RSD based on anecdotal evidence, however, they carry a risk of intentional overdose. Selective serotonin reuptake inhibitors (SSRIs) are not as prone to overdose however, they are also not as effective for the treatment of pain in RSD.

Tricyclic antidepressants that may be used in the treatment of RSD include:

• Amitriptyline (Elavil)
• Doxepin (Sinequan, Adapin)
• Nortriptyline (Pamelor, Aventyl)

Selective serotonin reuptake inhibitors (SSRIs) that may be effective for treatment of RSD include:

• Fluoxetine (Prozac)
• Sertraline (Zoloft)
• Paroxetine (Paxil)

Selective serotonin and norepinephrine reuptake inhibitors (SNRIs) have been shown to be effective in relieving chronic neuropathic pain and may be effective for RSD as well. They include:

• Venlafaxine (Effexor)
• Duloxetine (Cymbalta)

Side effects of antidepressants include:

• Nausea/vomiting
• Dry mouth
• Urine retention
• Sleep disruption
• Weight gain
• Anxiety

Bisphosphonates

Bisphosphonates target bone loss and have been studied more thoroughly than any other drugs for the treatment of RSD. Bisphosphonates that have undergone clinical trials include:

• Calcitonin (intranasal spray), administered in both nostrils, has been demonstrated to be an affective treatment for RSD pain.
• Clodronate (intravenous)
• Alendronate (intravenous)

Although most clinical trials showed significant improvement in active movement and motor function, there are some studies where the data regarding efficacy for treatment of RSD was inconclusive.

Side effects of bisphosphonates include:

• Fever and flu-like symptoms
• Hypocalcemia (low levels of calcium)
• Bone and joint pain. The U.S. Food and Drug Administration notes that some people taking bisphosphonates may experience severe and sometimes incapacitating bone, joint, and/or muscle (musculoskeletal) pain
• Kidney damage
• Osteonecrosis (breakdown of bone tissue) of the jaw
• Constipation or diarrhea

Muscle Relaxants

Muscle relaxants are used to control and provide relief from muscle cramps and muscle spasms that may be associated with RSD. Examples of muscle relaxants include:

• Clonazepam (Klonopin)
• Baclofen (Lioresal)

Side effects of muscle relaxants include:

• Drowsiness
• Dry mouth
• Dizziness
• Fatigue
• Nausea
• Unpleasant taste in the mouth
• Blurred vision

Adrenergic Active Drugs

Based on anecdotal evidence, many physicians use sympatholytic agents, medications that decrease the activity of the sympathetic nervous system, including:

• Clonidine (Catapres - oral or transdermal patch)
• Phenoxybenzamine (Dibenzyline)
• Reserpine (Harmonyl)

Studies have reported that intravenous phentolamine (Regitine) is not effective in controlling pain in RSD.

Although the mechanism of action is not entirely understood, it is thought that these adrenergic active drugs work by blocking the action of norepinephrine on nerve receptors that become active in neuropathic pain.

Side effects include:

• Nervousness
• Agitation
• Sleep disturbances

Corticosteroids

This class of drugs is used to reduce inflammation and swelling and has been used to control many types of pain for many years. After going through a period of not being used for RSD, they are once again being investigated in clinical trials for treatment of RSD-related pain. So far, corticosteroids, such as prednisone and methylprednisolone, have demonstrated good analgesic efficacy for patients with early-stage RSD. Patients must be monitored carefully for potentially serious side effects including susceptibility to infections and avascular necrosis of bone.

Other side effects include:

• Increased appetite
• Nervousness
• Indigestion
• Dizziness

Oral Opioids

This class of drugs may help relieve severe cases of RSD with widespread pain. Use of opioids for RSD is controversial, although it remains the gold standard of treatment for acute pain in general. The potential side effects, however, such as drug tolerance, addiction, and drowsiness are serious considerations.

Tramadol (Ultram) is an atypical opioid that is effective for chronic neuropathic pain and may be effective for RSD as well. It is not a controlled substance, like other opioids such as morphine, and also has less of an effect on the gastrointestinal tract (constipation, nausea) than classic opioids.

For further information regarding medications for chronic pain that may be effective for RSD as well, please click on the following link: http://www.ncbi.nlm.nih.gov/pubmed/17164107