Restless Legs Syndrome:
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Restless Legs Syndrome: Classification, Diagnosis and Approaches to Treatment Part 3 of 3
www.wemove.org RLS Slide Library Version 1.0 - All Contents Copyright © WE MOVE 2001
RLS Treatment Goals • • • •
Eliminate or minimize associated symptoms Reduce EDS Improve overall quality of life Improve activities of daily living
www.wemove.org
Overall Treatments • Nonpharmacologic • Pharmacological
www.wemove.org
Possible Underlying Disorders • Anemia • Folic acid deficiency • End-stage renal disease
www.wemove.org
Potential Aggravators of RLS • • • • •
Tobacco products Alcohol Caffeine Certain medications Sleep deprivation
www.wemove.org
Potentially Beneficial Strategies • Maintaining a regular sleep regimen • Sleeping late in the circadian cycle • Undertaking regular, moderate exercise
www.wemove.org
Additional Approaches • Tasks that engage the mind during sedentary periods • Bedtime massages • Hot baths • Cold packs or hot compresses
www.wemove.org
Scope of RLS Treatment • Established therapies are pharmacologic • No known cure • Therapy directed at symptomatic relief and improved ADLs and QOL
www.wemove.org
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 www.wemove.org
Dopaminergic Agents: First-line RLS Therapies • Dopamine agonists (DAs) • Dopamine precursors (levodopa)
www.wemove.org
Dopamine Agonists (DAs) Capable of alleviating all major symptoms of RLS • • • •
Bromocriptine Pergolide Pramipexole Ropinerole www.wemove.org
Dopamine Precursors Carbidopa/levodopa available as… • Sinemet® in 10/100, 25/100, or 25/250 • Sinemet®CR in 25/100, 50/200
www.wemove.org
Administration of Levodopa for RLS • PRN or on a regular schedule • One to 2 hours before bedtime • On an empty stomach, if possible
www.wemove.org
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
www.wemove.org
Higher Doses of Levodopa • Increased risk of augmentation • Worsening of symptoms
www.wemove.org
Adverse Effects of Levodopa • GI symptoms: nausea and vomiting, constipation or diarrhea, anorexia • Sleep disturbances: insomnia, fatigue • Other: anxiety, dry mouth, flushing, headache
www.wemove.org
Dopamine Agonists (DAs) • Ergotolines – Pergolide (Permax®) – Bromocriptine (Parlodel®)
• Nonergotolines – Pramipexole (Mirapex®) – Ropinirole (Requip™)
www.wemove.org
Ergot Derivatives • Pergolide (Permax®) • Bromocriptine (Parlodel®)
www.wemove.org
Pergolide Therapy for RLS • Long-acting • Higher relative potency than bromocriptine • Well-absorbed through GI tract
www.wemove.org
Initiation of DA Therapy • Relatively small dosage – 0.05 mg for pergolide – 1.25-2.50 mg for bromocriptine
• Slow titration upward
www.wemove.org
Advantages of Pergolide or Bromocriptine • Less augmentation than with carbidopa/levodopa • First-line therapy for patient with moderate or severe RLS
www.wemove.org
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
www.wemove.org
Nonergotoline DAs for RLS • Pramipexole (Mirapex®) • Ropinirole (Requip®)
www.wemove.org
Pramipexole Targets: Several RLS Symptoms
www.wemove.org
Key Benefits of Nonergotoline DAs • Possible effectiveness in non-responders to other DAs (i.e., ergotolines)
www.wemove.org
Initiating Pramipexole Therapy for RLS • Initiate with low dose of 0.125 mg/day or lower • Gradual titration to therapeutic range of 0.25 mg to 1.5 mg/day
www.wemove.org
Adverse Effects of DAs • • • • • • •
Nausea/vomiting Orthostatic hypertension Nasal congestion Insomnia Dizziness Lightheadedness Somnolence www.wemove.org
Other Drugs with Dopaminergic Action • Amantadine (Symmetrel®) • Selegiline (Eldepryl®)
www.wemove.org
Benzodiazepines for RLS • • • •
Clonazepam (Klonopin®) Temazepam (Restoril®) Diazepam (Valium®) Triazolam (Halcion®)
www.wemove.org
Benzodiazepine Issues for RLS • Schedule C-IV controlled substances • Low risk of tolerance/abuse
www.wemove.org
Role of Benzodiazepines in RLS • May be combined with dopamine agonists or carbidopa/levodopa • Most benefit – Mild and intermittent symptoms – Young patients
www.wemove.org
Daily Doses of Benzodiazepines for RLS • Clonazepam: 0.75 mg • Diazepam: 2.0 to 5.0 mg • Triazolam: 0.125 to 0.25 mg
www.wemove.org
AEs of Benzodiazepines • • • • • • •
Daytime somnolence “Hang over” Decreased libido Risk of falls Exacerbation of pre-existing sleep apnea Tolerance and dependency Withdrawal symptoms www.wemove.org
Opioids in the Treatment of RLS • Propoxyphene hydrochloride (Darvon®) • Codeine • Oxycodone hydrochloride (Percocet® or Roxicodone®) • Methadone hydrochloride
www.wemove.org
Administration of Opioids For RLS • Oral administration • Taken with food to minimize GI upset • Taken at bedtime
www.wemove.org
Adverse Effects of Opioids • • • • •
Nausea Constipation Mental changes Interaction with other CNS depressants Addiction
www.wemove.org
Other Pharmacologic Agents for RLS • Anticonvulsants – Carbamazepine (Tegretol®) – Gabapentin (Neurontin®)
• Antihypertensives – Clonidine hydrochloride (Catapres®)
www.wemove.org
Other Pharmacologic Agents for RLS • Antispasticity agents – Baclofen
• Mixed analgesics and sedative-hypnotics – Tramadol (Ultram®)
www.wemove.org
www.wemove.org RLS Slide Library Version 1.0 - All Contents Copyright © WE MOVE 2001
RLS Treatment Goals • • • •
Eliminate or minimize associated symptoms Reduce EDS Improve overall quality of life Improve activities of daily living
www.wemove.org
Overall Treatments • Nonpharmacologic • Pharmacological
www.wemove.org
Possible Underlying Disorders • Anemia • Folic acid deficiency • End-stage renal disease
www.wemove.org
Potential Aggravators of RLS • • • • •
Tobacco products Alcohol Caffeine Certain medications Sleep deprivation
www.wemove.org
Potentially Beneficial Strategies • Maintaining a regular sleep regimen • Sleeping late in the circadian cycle • Undertaking regular, moderate exercise
www.wemove.org
Additional Approaches • Tasks that engage the mind during sedentary periods • Bedtime massages • Hot baths • Cold packs or hot compresses
www.wemove.org
Scope of RLS Treatment • Established therapies are pharmacologic • No known cure • Therapy directed at symptomatic relief and improved ADLs and QOL
www.wemove.org
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 www.wemove.org
Dopaminergic Agents: First-line RLS Therapies • Dopamine agonists (DAs) • Dopamine precursors (levodopa)
www.wemove.org
Dopamine Agonists (DAs) Capable of alleviating all major symptoms of RLS • • • •
Bromocriptine Pergolide Pramipexole Ropinerole www.wemove.org
Dopamine Precursors Carbidopa/levodopa available as… • Sinemet® in 10/100, 25/100, or 25/250 • Sinemet®CR in 25/100, 50/200
www.wemove.org
Administration of Levodopa for RLS • PRN or on a regular schedule • One to 2 hours before bedtime • On an empty stomach, if possible
www.wemove.org
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
www.wemove.org
Higher Doses of Levodopa • Increased risk of augmentation • Worsening of symptoms
www.wemove.org
Adverse Effects of Levodopa • GI symptoms: nausea and vomiting, constipation or diarrhea, anorexia • Sleep disturbances: insomnia, fatigue • Other: anxiety, dry mouth, flushing, headache
www.wemove.org
Dopamine Agonists (DAs) • Ergotolines – Pergolide (Permax®) – Bromocriptine (Parlodel®)
• Nonergotolines – Pramipexole (Mirapex®) – Ropinirole (Requip™)
www.wemove.org
Ergot Derivatives • Pergolide (Permax®) • Bromocriptine (Parlodel®)
www.wemove.org
Pergolide Therapy for RLS • Long-acting • Higher relative potency than bromocriptine • Well-absorbed through GI tract
www.wemove.org
Initiation of DA Therapy • Relatively small dosage – 0.05 mg for pergolide – 1.25-2.50 mg for bromocriptine
• Slow titration upward
www.wemove.org
Advantages of Pergolide or Bromocriptine • Less augmentation than with carbidopa/levodopa • First-line therapy for patient with moderate or severe RLS
www.wemove.org
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
www.wemove.org
Nonergotoline DAs for RLS • Pramipexole (Mirapex®) • Ropinirole (Requip®)
www.wemove.org
Pramipexole Targets: Several RLS Symptoms
www.wemove.org
Key Benefits of Nonergotoline DAs • Possible effectiveness in non-responders to other DAs (i.e., ergotolines)
www.wemove.org
Initiating Pramipexole Therapy for RLS • Initiate with low dose of 0.125 mg/day or lower • Gradual titration to therapeutic range of 0.25 mg to 1.5 mg/day
www.wemove.org
Adverse Effects of DAs • • • • • • •
Nausea/vomiting Orthostatic hypertension Nasal congestion Insomnia Dizziness Lightheadedness Somnolence www.wemove.org
Other Drugs with Dopaminergic Action • Amantadine (Symmetrel®) • Selegiline (Eldepryl®)
www.wemove.org
Benzodiazepines for RLS • • • •
Clonazepam (Klonopin®) Temazepam (Restoril®) Diazepam (Valium®) Triazolam (Halcion®)
www.wemove.org
Benzodiazepine Issues for RLS • Schedule C-IV controlled substances • Low risk of tolerance/abuse
www.wemove.org
Role of Benzodiazepines in RLS • May be combined with dopamine agonists or carbidopa/levodopa • Most benefit – Mild and intermittent symptoms – Young patients
www.wemove.org
Daily Doses of Benzodiazepines for RLS • Clonazepam: 0.75 mg • Diazepam: 2.0 to 5.0 mg • Triazolam: 0.125 to 0.25 mg
www.wemove.org
AEs of Benzodiazepines • • • • • • •
Daytime somnolence “Hang over” Decreased libido Risk of falls Exacerbation of pre-existing sleep apnea Tolerance and dependency Withdrawal symptoms www.wemove.org
Opioids in the Treatment of RLS • Propoxyphene hydrochloride (Darvon®) • Codeine • Oxycodone hydrochloride (Percocet® or Roxicodone®) • Methadone hydrochloride
www.wemove.org
Administration of Opioids For RLS • Oral administration • Taken with food to minimize GI upset • Taken at bedtime
www.wemove.org
Adverse Effects of Opioids • • • • •
Nausea Constipation Mental changes Interaction with other CNS depressants Addiction
www.wemove.org
Other Pharmacologic Agents for RLS • Anticonvulsants – Carbamazepine (Tegretol®) – Gabapentin (Neurontin®)
• Antihypertensives – Clonidine hydrochloride (Catapres®)
www.wemove.org
Other Pharmacologic Agents for RLS • Antispasticity agents – Baclofen
• Mixed analgesics and sedative-hypnotics – Tramadol (Ultram®)
www.wemove.org
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