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Not all patients with restless legs syndrome will require pharmacological (drug) therapy. The decision whether or not to implement an individual treatment plan for idiopathic restless legs syndrome is based upon a variety of clinical factors including:

• Type and severity of the symptoms
• Frequency of symptoms
• How long the symptoms last
• Are symptoms related to restless legs syndrome or PLMD
• Are symptoms present during waking, sleeping, or both
• Is the patient experiencing leg pain, or leg discomfort
• Extent and type of sleep disturbances
• Effect of symptoms on the patient's overall function and quality of life
• Presence of other comorbidities such as neuropathy or heart disease, which may influence type and dose of medication chosen for therapy.

In general, the following classes of drugs may be used for the management of patients with restless legs syndrome:

• Dopaminergic agents
• Benzodiazepines
• Opioid medications
• Anticonvulsants

Dopaminergic Agents

Dopaminergic agents enhance the levels of dopamine which is the neurotransmitter (naturally produced chemical) that regulates the messages for movement between nerve cells in the central nervous system. They inhibit abnormal movement by enhancing the level of dopamine available and this facilitates the ease of messages passing between brain cells in the central nervous system. Dopaminergic agents are the first line treatment for restless legs syndrome and alleviate all major features of restless legs syndrome symptoms including:

• Restlessness
• Abnormal sensations
• Involuntary movements
• Sleep disturbances

Two important side effects associated with dopaminergic agents that must be continually assessed include:

• Rebound - the reappearance of symptoms when the dose wears off typically in the middle of the night or during early morning hours assuming the patient took medication before bedtime. This is often followed by a symptom-free period during the day and then symptoms re-emerge (sometimes stronger) at night. Rebound is preventable by using controlled release formulation or by adding a dose in the middle of the night.

• Augmentation - this is a more significant side effect and occurs in 50-80% of patients using levodopa. Some patients may have to change medication when augmentation occurs. It may begin within a few months after initiating treatment with levodopa and consists of :

  • initiation of restless legs syndrome symptoms earlier in the day
  • a more rapid onset of symptoms when the patient is at rest
  • increased severity of symptoms
  • shorter relief from dopaminergic medications
  • symptoms may spread from the legs to the arms.

The severity of restless legs syndrome symptoms and dosage of dopaminergic agents are related to the likelihood of augmentation occurring. In the short term, augmentation may be treated by increasing the frequency of administration of levodopa but over time, the period of effectiveness may continue to shorten. At that point, the medication may have to be discontinued and a new one initiated. Administration of single medications is recommended as the first choice, however, switching medications and/or combining them until the most effective regimen is established, may be necessary in the treatment of restless legs syndrome. If restless legs syndrome is intractable, combination therapy or use of opioids may be needed. There is little data regarding drug combinations for treating restless legs syndrome but it appears that side effects are more likely to occur when drugs are combined than when taken alone.