eMedicine Specialties > Neurology > Sleep-Related Diseases
Periodic Limb Movement Disorder: Treatment & Medication
Updated: Aug 26, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Patient reassurance is essential.
Consultations
Because the differential diagnosis of periodic limb movement disorder includes seizure and other forms of myoclonus, a neurology consultation is indicated to exclude other conditions.
Medication
Therapy does not modify the disease but does relieve symptoms. The arsenal of medication options is expanding and includes dopaminergic medications10,11 , antiepileptic agents, and even opioids, although the controlled substances may not be appropriate first-line agents. Because most studies focused on restless legs syndrome, a similar and related (but separate) disorder, the best treatments for periodic limb movement are not known. However, using restless legs syndrome guidelines, dopaminergic agents are first-line treatment.
Benzodiazepines
The efficacy of clonazepam in reducing the total number of periodic limb movements per hour has been reported.12,13
Clonazepam (Klonopin)
Useful in suppressing muscle contractions by facilitating action of GABA and other inhibitory neurotransmitters.
Adult
0.5-3 mg PO qhs; in some cases, tid schedule used
Pediatric
Not established
Clearance may be increased and effects reduced by phenytoin and barbiturates; toxicity of benzodiazepines in CNS significantly increased when used concurrently with other CNS depressants
Documented hypersensitivity; severe liver disease; acute narrow-angle glaucoma
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Causes sedation; should not be used with alcohol; habit forming; use caution in patients with chronic respiratory disease or impaired renal function; withdrawal symptoms can result from abrupt discontinuation
Dopaminergic agents
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.14
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).
Adult
Effective dose varies; can be as low as 10/100 mg PO qhs
Pediatric
Not established
Effects decreased by hydantoins, pyridoxine, phenothiazine, and hypotensive agents; toxicity increased by antacids or MAOIs.
Documented hypersensitivity; narrow-angle glaucoma; malignant melanoma; undiagnosed skin lesions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Certain adverse CNS effects (eg, dyskinesias) occur at lower dosages and earlier in therapy with sustained release form; use caution in patients with history of myocardial infarction, arrhythmias, asthma, peptic ulcer disease; may worsen Parkinson disease if discontinued suddenly; patients on high-protein diets should distribute protein intake throughout day to avoid fluctuations in levodopa absorption
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.
Adult
0.05 mg/d PO initial dose; titrate to > 1 mg/d in divided doses
Pediatric
Not established
Use caution with dopamine antagonists such as antipsychotics and gastric motility agents; use with levodopa may cause or exacerbate preexisting states of confusion and hallucinations or dyskinesia; because >90% bound to plasma proteins, use caution if coadministered with other drugs known to affect protein binding
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Adverse effects include hypotension; use caution in patients who have been treated for cardiac dysrhythmias
Anticonvulsants
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.
Adult
300 mg/d PO initial dose; increase by 300 mg/d each week until 900 mg tid or 1200 mg tid; more rapid titration appears to increase somnolence and dizziness
Pediatric
Not established
Bioavailability may be reduced significantly by antacids–wait > 2 h following antacid administration; may increase norethindrone levels significantly
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use caution in severe renal disease and elderly patients
Skeletal muscle relaxants
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.
Adult
5 mg (1/2 tab) PO qhs; increase slowly to avoid sedation and other adverse effects, by 10 mg/d q5d; not to exceed 40 mg tid
Pediatric
Not established
Effects may be increased by opiate analgesics, benzodiazepines, alcohol, tricyclic antidepressants, guanabenz, MAOIs, clindamycin, and hypertensive agents
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Use caution when spasticity utilized to obtain increased function and in patients with history of autonomic dysreflexia; withdrawal can cause autonomic dysreflexia; use caution in renal impairment
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.
Adult
4-8 mg PO hs; titration may begin at 2 mg hs with an increase of 2-4 mg/wk
Pediatric
Not studied for the off-label use of PLM disorder
Cleared more rapidly in patients treated with carbamazepine, phenytoin, primidone, and phenobarbital than in patients not treated with these drugs
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
For on-label use, patients receiving valproate monotherapy may require lower doses or a slower dose titration for clinical response; moderately severe to incapacitating generalized weakness has been reported following administration in up to 1% of patients with epilepsy; weakness may resolve after reduction in dose or discontinuation of drug; should be withdrawn slowly to reduce potential for increased seizure frequency; slow titration is recommended, beginning at 2 mg hs
More on Periodic Limb Movement Disorder |
| Overview: Periodic Limb Movement Disorder |
| Differential Diagnoses & Workup: Periodic Limb Movement Disorder |
 Treatment & Medication: Periodic Limb Movement Disorder |
| Follow-up: Periodic Limb Movement Disorder |
| References |
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References
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Further Reading
Keywords
periodic limb movement disorder, PLM, restless leg syndrome, RLS, nocturnal myoclonus, sleep disorders, PLMS, periodic limb movements during sleep, ADHD, attention deficit hyperactivity disorder, PLM disorder, diabetes mellitus, spinal cord tumor, sleep apnea syndrome, narcolepsy, uremia, anemia, sleep disturbances, sleep apnea
