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• Sleep apnea (may develop or become exacerbated)
• Drug dependence (low risk)

Benzodiazepines should not be taken with alcohol or any other medication that depresses the central nervous system.

Examples of benzodiazepines that may be used for the treatment of restless legs syndrome include:

• Clonazepam (Klonopin) - this is the most commonly used drug in this category. Its side effect is early morning sedation.
• Diazepam (Valium) - helpful in up to 75% of patients
• Alprazolam (Xanax)
• Temazepam (Restoril)

Opioid Medications

Opioid medications possess both analgesic (pain-relieving) and sedative properties and have been found to be useful for the treatment of both restless legs syndrome and periodic limb movement. Low potency opioids such as propoxyphene hydrochloride (Darvon) alleviate all major symptoms of restless legs syndrome and have been shown to be effective for up to 15 years with little risk of dependence and few side effects. Higher potency opioids such as oxycodone hydrochloride (Percocet) are effective for patients with severe restless legs syndrome who have not responded to other types of medications. In a study of 500 patients with restless legs syndrome, approximately 20% reported taking opioids at some point either as a solo drug or in combination with other drugs for an average of 6 years. Opioids can also be taken as a single dose to prevent symptoms for a specific period of time (e.g. plane trip or going to the theatre).

Examples of drugs in this category include:

• Morphine
• Codeine
• Oxycodone
• Hydrocodone
• Propoxyphene
• Methadone - this drug usually provides longer-acting relief and is given for the most refractory cases of restless legs syndrome (i.e., individuals who don't respond to other medications)

Side-effects of opioid medications include drowsiness, constipation, confusion, and the potential for drug addiction (a major concern). Daytime augmentation is rare but symptoms return when the medication is withdrawn and sometimes they are temporarily worse than before.

There is no general consensus as to whether opioids should be used as second-line treatment or reserved to be used as a last resort. Since each individual responds differently to specific medications, sometimes it takes several "trial and error" attempts before the right drug and the right dose is identified.

Anticonvulsants

This class of drugs has also been found to be helpful for controlling some of the symptoms of restless legs syndrome, such as restlessness, sensory abnormalities, sleep problems, and painful peripheral neuropathy. The most commonly drugs in this category include:

• Gabapentin (Neurontin)
• Carbamazepine (Tegretol)

Both of these drugs are usually well-tolerated although gabapentin has become preferred because of lower risk of side effects which may include:

• Fatigue (more of a problem with carbamazapine)
• Dizziness
• Gastrointestinal upset (this is minimized by taking the medication with food)
• Carbamazepine carries a warning concerning the risk of aplastic anemia