Medication Summary
Therapy does not modify the disease but does relieve symptoms. The arsenal of medication options is expanding and includes dopaminergic medications, [29, 30, 31] antiepileptic agents, and even opioids, although the controlled substances may not be appropriate first-line agents. Although the benzodiazepine clonazepam has been shown to reduce the number of periodic limb movements per hour in periodic limb movement disorder (PMLD) patients, PLMD comorbid with RBD has been associated with a poor treatment response to clonazepam monotherapy. [32] Because most studies focused on restless legs syndrome (RLS), a similar and related (but separate) disorder, the best treatments for PLMD are not known. However, using RLS guidelines, dopaminergic agents are first-line treatment.
Benzodiazepines
Class Summary
The efficacy of clonazepam in reducing the total number of periodic limb movements per hour has been reported. [33, 34] However, benzodiazepines are not without risk, especially for certain patient populations, and thus their use should be carefully considered.
Clonazepam (Klonopin)
Useful in suppressing muscle contractions by facilitating action of GABA and other inhibitory neurotransmitters.
Dopaminergic agents
Class Summary
The levodopa/carbidopa combination has been considered an effective treatment for this condition in specific patients; on the other hand, some studies suggest that the medication may be the etiology of secondary periodic limb movement disorder in other patients. Pieta and colleagues studied pergolide in patients with secondary periodic limb movement disorder caused by uremia and found subjective improvement in sleep quality and objective reduction in limb movements during the first hour of sleep; however, no objective improvement in sleep architecture was observed. [35]
Ropinirole (Requip, Requip XL)
Second-generation, nonergoline dopamine agonist that directly stimulates dopamine receptors in the brain. Possesses high specificity for D3 receptor subtype. Indicated for moderate-to-severe restless legs syndrome.
Pramipexole (Mirapex, Mirapex ER)
D2 and D3 receptor agonist recently approved by FDA for treating Parkinson disease; also used effectively in patients with restless legs syndrome.
Carbidopa/levodopa (Sinemet)
Large neutral amino acid absorbed in proximal small intestine by saturable carrier-mediated transport system. Absorption decreased by meals, which include other large neutral amino acids. However, only patients with meaningful motor fluctuations need consider low-protein or protein-redistributed diet. Greater consistency of absorption achieved when levodopa taken > 1 h after meals. Nausea often reduced if taken immediately following meals. Some patients with nausea benefit from additional carbidopa up to 200 mg/d.
Half-life approximately 2 h.
Most common acute adverse effects are nausea, hypotension, and hallucinations. Long-term adverse effects include motor fluctuations and dyskinesia (chorea).
Pergolide (Permax)
Pergolide was withdrawn from the US market March 29, 2007, because of heart valve damage resulting in cardiac valve regurgitation. It is important not to abruptly stop pergolide. Health care professionals should assess patients' need for dopamine agonist (DA) therapy and consider alternative treatment. If continued treatment with a DA is needed, another DA should be substituted for pergolide. For more information, see FDA MedWatch Product Safety Alert and Medscape Alerts: Pergolide Withdrawn From US Market.
Studies in patients with secondary PLM disorder caused by uremia revealed subjective improvement in sleep quality and objective reduction in limb movements during first hour of sleep; however, no objective improvement in sleep architecture was observed.
Anticonvulsants
Class Summary
These agents are useful in managing severe muscle spasms.
Gabapentin (Neurontin)
Mechanism of action uncertain; although has GABA-like structure, action at GABA receptors not shown clearly. Fortunately, considered relatively safe and thus may be considered for PLM disorder.
Skeletal muscle relaxants
Class Summary
These agents exert their effects by inhibiting release of excitatory neurotransmitters.
Baclofen (Lioresal)
GABA agonist at slower potassium channels in cerebellum and spinal cord. May have efficacy in PLM disorder. Because works in spinal cord and less in brain cortex, calls into question neurologic origin of PLM.
Tiagabine (Gabitril)
Antiepileptic agent FDA approved for adjunctive treatment of certain seizure types. Recent evidence supports use in PLM disorder possibly because of GABA enhancing activity or because of improved sleep quality. FDA approved for seizures at doses up to 56 mg/d. Evidence suggests that use for PLM disorder requires far lower doses, possibly 4-8 mg at bedtime.
