Restless Legs Syndrome and Related Disorders - Medications

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Benzodiazepines

Benzodiazepines, such as clonazepam (Klonopin), are commonly called sedative hypnotics and are used for insomnia and anxiety. They may be helpful for some patients with RLS that disrupts sleep. Clonazepam may be particularly helpful for children with both periodic limb movement disorder and symptoms of attention-deficit hyperactivity disorder. It also appears to be helpful for patients with RLS who are undergoing hemodialysis.

Side Effects. Elderly people are more susceptible to side effects and should usually start at half the dose prescribed for younger people and should not take long-acting forms. Side effects may differ depending on whether the benzodiazepine is long- or short-acting.

• The drugs may increase depression, a common co-condition in any case in many people with insomnia.
• Breathing problems may occur with overuse or with people with pre-existing respiratory illness.
• Long-acting drugs have a very high rate of residual daytime drowsiness compared to others. They have been associated with a significantly increased risk for automobile accidents and falls in the elderly particularly in the first week after taking them. Shorter-acting benzodiazepines do not appear to pose as high a risk.
• Memory loss (so-called traveler's amnesia), sleepwalking, and odd mood states have been reported after taking triazolam (Halcion) and other short-acting benzodiazepines. These effects are rare and probably enhanced by alcohol.
• Because these drugs cross the placenta and enter breast milk, pregnant nursing women should not use them. An association was reported between the use of benzodiazepines in the first trimester of pregnancy and the development of cleft lip in newborns.
• In rare cases, overdoses have been fatal.

Interactions. Benzodiazepines are potentially dangerous when used in combination with alcohol. Some drugs such as the ulcer medication cimetidine can slow the breakdown of the benzodiazepine.

Withdrawal Symptoms. Withdrawal symptoms usually occur after prolonged use and indicate dependence. They can last 1 - 3 weeks after stopping the drug and may include:

• Gastrointestinal distress
• Sweating
• Disturbed heart rhythm
• In severe cases, patients might hallucinate or experience seizures, even a week or more after the drug has been stopped.

Rebound Insomnia. Rebound insomnia, which often occurs after withdrawal, typically includes one to two nights of sleep disturbance, daytime sleepiness, and anxiety. The chances for rebound are higher with the short-acting benzodiazepines than with the longer-acting ones.

Narcotic Pain Relievers

Narcotics are pain-relieving drugs that act on the central nervous system. They are sometimes prescribed for severe cases of RLS. They may be a good choice if pain is a prominent feature. Some evidence also suggests that narcotics reduce the frequency of periodic leg movements.

There are two types of narcotics, both of which have been used in RLS:

• Opiates are derived from natural opium (morphine and codeine). Some patients report relief with the use of the opiate fentanyl (Duragesic), used in skin patch form. An implanted abdominal pump (Isomed) uses morphine and an anesthetic called bupivacaine. Investigate work is showing promise for patients with severe RLS.
• Opioids are synthetic drugs. The most common example is oxycodone (Percodan, Percocet, Roxicodone, Oxycontin). Apomorphine is a morphine derivative. In one study, when it was injected under the skin at night, it reduced nocturnal discomfort and leg movements in some patients.

Although the use of narcotics for severe RLS is controversial, some studies have suggested that they are rarely addictive for pain sufferers except among patients with a history of substance abuse, even when they are prescribed long-term. The use of such drugs may be beneficial when included as part of a comprehensive pain management program. Such a program involves screening prospective patients for possible drug abuse and then regularly monitoring those who are taking it, adjusting the dose as necessary to achieve an acceptable balance between pain relief and side effects. Patients on long-term opiate therapy should also be monitored periodically for sleep apnea, a condition that causes breathing to stop for short periods many times during the night and which may exacerbate symptoms of RLS, insomnia, and other complaints.

Tramadol. Tramadol (Ultram) is a pain reliever that has been used as an alternative to opioids. In one study, tramadol was very effective for RLS and produced few or no side effects. It has opioid-like properties, but is not as addictive. (Dependence and abuse have been reported, however.) Nevertheless, withdrawal after long-term use (longer than a year) can cause intense symptoms, including diarrhea, insomnia, and even restless legs syndrome itself.

Antiseizure Drugs

Antiseizure drugs, such as gabapentin (Neurontin), valproic acid (valproate, divalproex, Depakote, Depakene), and carbamazepine (Tegretol), relax blood vessels and are being tested for RLS. Gabapentin, a newer antiseizure drug, is showing particular promise for mild to moderate RLS. A 2002 study reported that it improved RLS symptoms and sleep, particularly in patients who also experienced pain. It was also effective for periodic leg movement disorder.

Side Effects. All antiseizure drugs have potentially severe side effects and should be tried only after non-drug methods have failed. Side effects of many anti-seizure drugs include nausea, vomiting, heartburn, increased appetite with weight gain, hand tremors, irritability, and temporary hair thinning and loss (taking zinc and selenium supplements may help reduce this effect). Some can also cause birth defects and, in rare cases, liver toxicity. Gabapentin may have fewer of these side effects than valproic acid or carbamazepine.

Other Drugs

Selective Serotonin Reuptake Inhibitors (SSRIs) and Similar Antidepressants. Imbalances in the neurotransmitter serotonin have been associated with RLS. To correct these imbalances, some patients can try the common antidepressants known as SSRIs, which increase serotonin levels in the brain. One study found that SSRIs reduced RLS in 58% of patients and eliminated symptoms in 12%. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), and citalopram (Celexa, Cipramil).

Bupropion (Wellbutrin), a newer so-called designer antidepressant that has slightly different actions, may also be helpful for RLS. These drugs are not addictive and do not have the severe side effects of other RLS drugs, but more research is warranted to determine if they are useful.

Clonidine. Clonidine (Catapres), a drug used for high blood pressure, is helpful for some patients and may be an appropriate choice for patients who have RLS accompanied by hypertension. It also may help patients with RLS who are undergoing hemodialysis.

Baclofen. The anti-spasm drug baclofen (Lioresal) appears to reduce intensity of RLS (although not frequency of movements).

Review Date: 10/18/2006
Reviewed By: Harvey Simon, M.D., Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital