RLS Slide Library Version All Contents Copyright © WE MOVE 2001 Restless Legs Syndrome: Classification, Diagnosis and Approaches to Treatment Part 3 of 3

RLS Treatment Goals Eliminate or minimize associated symptoms Reduce EDS Improve overall quality of life Improve activities of daily living

Overall Treatments Nonpharmacologic Pharmacological

Possible Underlying Disorders Anemia Folic acid deficiency End-stage renal disease

Potential Aggravators of RLS Tobacco products Alcohol Caffeine Certain medications Sleep deprivation

Potentially Beneficial Strategies Maintaining a regular sleep regimen Sleeping late in the circadian cycle Undertaking regular, moderate exercise

Additional Approaches Tasks that engage the mind during sedentary periods Bedtime massages Hot baths Cold packs or hot compresses

Scope of RLS Treatment Established therapies are pharmacologic No known cure Therapy directed at symptomatic relief and improved ADLs and QOL

Start Treatment

Initiation of Drug Therapy Review medical history and current drug regimen Use single drug, when possible, for comorbidities PRN meds for episodic RLS Use minimal effective dose Treatment during early evening hours

Dopaminergic Agents: First-line RLS Therapies Dopamine agonists (DAs) Dopamine precursors (levodopa)

Dopamine Agonists (DAs) Capable of alleviating all major symptoms of RLS Bromocriptine Pergolide Pramipexole Ropinerole

Dopamine Precursors Carbidopa/levodopa available as… Sinemet ® in 10/100, 25/100, or 25/250 Sinemet ® CR in 25/100, 50/200

Administration of Levodopa for RLS PRN or on a regular schedule One to 2 hours before bedtime On an empty stomach, if possible

Dosage of Carbidopa/levodopa for RLS Initially 12.5/50 mg/day to 25/100 mg/day of regular formulation for symptoms for waking with symptoms at night 25/100 mg/day of controlled-release formulation useful at bedtime/sleep onset

Higher Doses of Levodopa Increased risk of augmentation Worsening of symptoms

Adverse Effects of Levodopa GI symptoms: nausea and vomiting, constipation or diarrhea, anorexia Sleep disturbances: insomnia, fatigue Other: anxiety, dry mouth, flushing, headache

Dopamine Agonists (DAs) Ergotolines –Pergolide (Permax ® ) –Bromocriptine (Parlodel ® ) Nonergotolines –Pramipexole (Mirapex ® ) –Ropinirole (Requip™)

Ergot Derivatives Pergolide (Permax ® ) Bromocriptine (Parlodel ® )

Pergolide Therapy for RLS Long-acting Higher relative potency than bromocriptine Well-absorbed through GI tract

Initiation of DA Therapy Relatively small dosage –0.05 mg for pergolide – mg for bromocriptine Slow titration upward

Advantages of Pergolide or Bromocriptine Less augmentation than with carbidopa/levodopa First-line therapy for patient with moderate or severe RLS

Adverse Effects Specific to Pergolide and Bromocriptine Contraindication: known hypersensitivity to ergot alkaloids Rare complications: –Pulmonary or retroperitoneal fibrosis –Pleural thickening and effusions Reddened, edematous skin changes in legs

Nonergotoline DAs for RLS Pramipexole (Mirapex ® ) Ropinirole (Requip ® )

Pramipexole Targets: Several RLS Symptoms

Key Benefits of Nonergotoline DAs Possible effectiveness in non-responders to other DAs (i.e., ergotolines)

Initiating Pramipexole Therapy for RLS Initiate with low dose of mg/day or lower Gradual titration to therapeutic range of 0.25 mg to 1.5 mg/day

Adverse Effects of DAs Nausea/vomiting Orthostatic hypertension Nasal congestion Insomnia Dizziness Lightheadedness Somnolence

Other Drugs with Dopaminergic Action Amantadine (Symmetrel®) Selegiline (Eldepryl®)

Benzodiazepines for RLS Clonazepam (Klonopin ® ) Temazepam (Restoril ® ) Diazepam (Valium ® ) Triazolam (Halcion ® )

Benzodiazepine Issues for RLS Schedule C-IV controlled substances Low risk of tolerance/abuse

Role of Benzodiazepines in RLS May be combined with dopamine agonists or carbidopa/levodopa Most benefit –Mild and intermittent symptoms –Young patients

Daily Doses of Benzodiazepines for RLS Clonazepam: 0.75 mg Diazepam: 2.0 to 5.0 mg Triazolam: to 0.25 mg

AEs of Benzodiazepines Daytime somnolence “Hang over” Decreased libido Risk of falls Exacerbation of pre-existing sleep apnea Tolerance and dependency Withdrawal symptoms

Opioids in the Treatment of RLS Propoxyphene hydrochloride (Darvon ® ) Codeine Oxycodone hydrochloride (Percocet ® or Roxicodone ® ) Methadone hydrochloride

Administration of Opioids For RLS Oral administration Taken with food to minimize GI upset Taken at bedtime

Adverse Effects of Opioids Nausea Constipation Mental changes Interaction with other CNS depressants Addiction

Other Pharmacologic Agents for RLS Anticonvulsants –Carbamazepine (Tegretol ® ) –Gabapentin (Neurontin ® ) Antihypertensives –Clonidine hydrochloride (Catapres ® )

Other Pharmacologic Agents for RLS Antispasticity agents –Baclofen Mixed analgesics and sedative-hypnotics –Tramadol (Ultram ® )