Stamford Marriott

1
2008
Symposia Series 1

• Stamford Marriott
• Stamford, Connecticut
• April 26, 2008

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1
2
Restless Legs Syndrome Recent Learnings and
Strategies
Michael J. Thorpy, MD Professor of
Neurology Albert Einstein College of
Medicine Director, Sleep-Wake Disorders
Center Department of Neurology Montefiore Medical
Center Bronx, New York
2
3
How many RLS patients have youtreated or
referred in the last month?

1. 0-5
2. 5-10
3. 10-20
4. gt20

Use your keypad to vote now!
RLS restless legs syndrome
4
Faculty Disclosure

• Dr Thorpy honorarium/speakers bureau Boehringer
  Ingelheim, GlaxoSmithKline

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5
Learning Objectives

• Identify the 4 primary clinical characteristics
  of RLS
• Design an individualized RLS management strategy
  based on disease severity
• Counsel patients on the nonpharmacologic and
  pharmacologic approaches to the management of
  RLS
• List the safety and efficacy profiles of
  pharmacologic agents available for the
  treatment of RLS

6
RLS Definition

• RLS is a neurologic disorder characterized by an
  uncontrollable urge to move the legs that usually
  is associated with unpleasant sensations
• Sensations range in severity from uncomfortable
  to irritating to painful

7
RLS Core SymptomsURGE

• Urge to move limbs, usually accompanied or
  caused by uncomfortable and unpleasant feelings
  in the limbs
• Rest or inactivity precipitates or worsens
  symptoms
• Getting up or moving improves the sensation
• Evening or nighttime appearance or worsening of
  symptoms

Courtesy of Philip M. Becker, MD. Allen RP, et
al. Sleep Med. 20034101-119 Walters AS. Mov
Disord. 199510634-642.
8
RLS Prevalence
8

• Overall prevalence 5-10
• Lower in Asian populations?
• Higher in women
• Up to 20 of patients in primary care have RLS
  symptoms
• Prevalence increases with age
• Mean age of onset 34 ? 20 years
• Can appear in childhood

RLS Patients (n 416)
All
6
Men
Women
4
Prevalence ()
2
0
20-29
30-39
40-49
50-59
60-69
70-79
?80
Age Group (years)
16,202 adults in the United States and5 European
countries
Allen R, et al. Arch Intern Med.
20051651286-1292 Hening W, et al. Sleep Med.
20045237-246 Kageyama T, et al. Psychiatry
Clin Neurosci. 200054296-298 Nichols D, et al.
Arch Intern Med. 20031632323-2329 Ondo W,
Jankovic J. Neurology. 1996471435 Phillips B,
et al. Arch Intern Med. 20001602137-2141 Ulfber
g J, et al. Eur Neurol. 20014617-19.
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RLS Video
SleepMultiMedia, Sleep Multimedia, Inc.,
Scarsdale, NY.
10
RLS Underdiagnosed in Primary Care
70
64.8
Reported RLS
60
64.8
Received diagnosis
50
37.9
40
Patients ()
37.9
30
24.9
20
12.9
24.9
10
12.9
0
Reported by Patients
Reported by Physicians
Hening W, et al. Sleep Med. 20045237-246.
11
Commonly Misdiagnosed

• Lack of understanding of RLS contributes to
  misdiagnosis
• May be tendency to attribute symptoms to
  better-recognized conditions
• Poor circulation
• Arthritis
• Back/spinal injury or problem
• Varicose veins
• Depression/anxiety
• Nerve compression

Allen RP, et al. Arch Intern Med.
20051651286-1292.
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2005 Sleep in America Poll Correlates of RLS

• Individuals with RLS were significantly more
  likely to
• Be unemployed
• Be cigarette smokers
• Have concomitant medical conditions

Net At least 1 condition
61
High blood pressure
29
Arthritis
28
Heartburn or GERD
19
Depression
18
Anxiety disorder
12
Diabetes
11
Heart disease
10
Lung disease
5
None of these
39
100
80
60
40
20
0
GERD gastroesophageal reflux disease. National
Sleep Foundation. Sleep in America Poll. 2005.
Available at www.sleepfoundation.org Accessed
March 6, 2008.
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Scope of the Problem
14
Burden of Illness

• Discomfort and pain
• Major cause of sleep disturbance
• Trouble falling asleep, decreased hours of sleep
• May lead to daytime fatigue/sleepiness
• Poor functioning at home or job
• Trouble sitting still, restless
• Impaired social interactions
• Feelings of frustration, anxiety, depression,
  embarrassment

Allen R, et al. Presented at 7th Congress of the
European Federation of Neurological Societies.
Abstract 576 Fehnel S, et al. 7th Congress of
the European Federation of Neurological
Societies. Abstract 677 Hening W, et al. 7th
Congress of the European Federation of
Neurological Societies. Abstract 605.
15
REST General Population StudyRLS Impact on
Quality of Life vs Age- and Sex-Adjusted US Norms
RLS patients
Age- and sex-adjusted norms for the US general
population (n 2474)
PhysicalFunctioning
RolePhysical
BodilyPain
GeneralHealth
Energy/Vitality
SocialFunctioning
RoleEmotional
MentalHealth
SF-36 Health Survey Domain
Scores for RLS sufferer groups were
significantly below the norms for all 8
dimensions. REST RLS Epidemiology, Symptoms,
and Treatment. Allen R, et al. Arch Intern Med.
20051651286-1292.
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REST General Population StudyRLS Impact on
Quality of Life Comparable to Chronic Conditions
RLS Patients (n 158)Patients in the US
General Population With Type 2 diabetes
mellitus (n 541) Osteoarthritis with
hypertension (n 175) Depression (n 502)
100
80
60
Mean Score
40
20
0
PhysicalFunctioning
RolePhysical
BodilyPain
GeneralHealth
Energy/Vitality
SocialFunctioning
RoleEmotional
MentalHealth
SF-36 Health Survey Domain
Allen R, et al. Arch Intern Med.
20051651286-1292.
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2005 Sleep in America Poll RLS Impact on
Daytime Function
Drive Drowsy
Participants at risk for RLS
Missed Events
Participants with no RLS risk
Errors at Work
Missed Work
P lt.05, at risk of RLS vsnot at risk of RLS
Late to Work
Fatigue
0
20
40
60
80
National Sleep Foundation. Sleep in America Poll.
2005. Available at www.sleepfoundation.org.
Accessed March 6, 2008.
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Sleep Heart StudyRLS Associated With CAD and CVD
Total No. Subjects 3433 No RLS 3254 RLS 179 2.05 (1.38-3.04) 2.07 (1.43-3.00)

CAD CVD
Frequency (per month) 5-15 53 1.34 (0.62-2.92) 1.53 (0.76-3.07)
Frequency (per month) 16-23 50 2.83 (1.40-5.71) 3.53 (1.85-6.76)
Frequency (per month) 24 76 2.14 (1.19-3.86) 1.75 (0.99-3.09)
CAD coronary artery disease CVD
cardiovascular disease. Winkelman JW, et al.
Neurology.20087035-42.
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Pathophysiology
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RLS Pathophysiology

• Serendipitous finding that low doses of levodopa
  provide relief from RLS
• Hypothesis RLS is associated with dopaminergic
  (DA) dysfunction in the CNS at the subcortical
  level
• CNS central nervous system.

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RLS What We Know About Its Pathophysiology
Genetic Factors Are Important Iron Status Appears Important Dopamine and Opioid Pathways May Play a Role Localization Within CNS Unknown
Primary accounts for most cases Majority are hereditary Highly significant gene associations found Possible rolewith dopamine Serum ferritin levels negatively correlate with symptoms Oral iron increases brain iron improves symptoms Dopamine agonists andopioids improve symptoms Naloxone exacerbates RLS in opioid treated patients Dopamine receptor blocker antagonized opioid effects PET/SPECT inconsistent RLS and Parkinsons association Dopamine synthesis is iron-dependent Some evidence of dopaminergic dysfunction from brain imaging Abnormal central iron homeostasis suggested
PET/SPECT positron emission tomography/single-ph
oton emission computed tomography. Allen RP, et
al. J Clin Neurophysiol. 200118128-147 Bogan
RK. Expert Opin Pharmacother. 20089611-623
Walters AS. Sleep Med. 20023301-304.
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RLS Pathophysiology Iron-Dopamine Model of RLS
Brain Iron Insufficiency
CNS Dopamine Abnormalities
RLS
Allen RP, et al. J Clin Neurophysiol.
200118128-147.
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RLS Primary vs Secondary

• Primary (idiopathic)
• Accounts for most cases
• Majority are hereditary (mainly autosomal
  dominant)
• Highly significant gene associations on
  chromosomes 6 and 2
• Secondary causes of RLS include
• Iron-deficiency anemia (25 of patients)
• Pregnancy (20 of pregnant women)
• End-stage renal disease/dialysis (up to 60)
• Medications
• Diabetes
• Rheumatoid arthritis
• Peripheral neuropathy

Bonati MT, et al. Brain. 20031261485-1492
Desautels A, et al. Am J Hum Genet.
2001691266-1270 Earley CJ, et al. J Neurosci
Res. 200062623-628 Hui DS, et al. Am J Kidney
Dis. 200036783-788 Lee KA, et al. J Womens
Health Gend Based Med. 200110335-341 National
Heart, Lung, and Blood Institute Working Group on
Restless Leg Syndrome. Am Fam Physician.
200062108-114 Tan EK, et al. Am J Med Sci.
2000319397-403.
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Agents That May Precipitate RLS

• Medications
• Antihistamines
• Dopamine antagonists
• Lithium
• Selective serotonin reuptake inhibitors (SSRIs)
• Tricyclic antidepressants
• Other
• Alcohol
• Caffeine
• Smoking

Parker KP, Rye DB. Nurs Clin North Am.
200237655-673 Stiasny K, et al. Sleep Med Rev.
20026253-265.
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Diagnosis
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Which of the following is necessary to establish
a diagnosis of RLS?

1. Brain MRI study
2. History and physical exam
3. Overnight polysomnogram (sleep study)
4. Serum ferritin level

Use your keypad to vote now!
MRI magnetic resonance imaging
27
RLS Assessment

• Patient history is essential
• Physical examination, including neurologic and
  vascular
• Will be normal if RLS is idiopathic
• Laboratory tests
• CBC
• Serum ferritin
• Percent iron saturation
• Folate
• Chemistries (BUN/creatinine ratio)
• FBG
• A1C

BUN blood urea nitrogen CBC complete blood
count FBG fasting blood glucose. Allen R, et
al. Sleep Med. 20034101-119 Parker KP, et al.
Nurs Clin North Am. 200237655-673.
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RLS Core SymptomsURGE

• Urge to move limbs, usually accompanied or
  caused by uncomfortable and unpleasant feelings
  in the limbs
• Rest or inactivity precipitates or worsens
  symptoms
• Getting up or moving improves the sensation
• Evening or nighttime appearance or worsening of
  symptoms

Courtesy of Philip M. Becker, MD. Allen RP, et
al. Sleep Med. 20034101-119 Walters AS. Mov
Disord. 199510634-642.
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The Simple Question

• The International RLS Study Group has devised the
  following question to determine which patients
  are likely to have RLS
• When you try to relax in the evening or sleep at
  night, do you ever have unpleasant, restless
  feelings in your legs that can be relieved by
  walking or movement?
• If your patient answers, Yes, he or she
  probably has RLS
• If your patient answers, No, he is unlikely to
  have RLS

Ferri R, et al. Eur J Neurol. 2007141016-1021.
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Differential Diagnosis

• Periodic limb movement disorder (PLMD)
• Semirhythmic leg movements during sleep
• Peripheral neuropathy
• More constant pain/discomfort not usually
  relieved by movement
• Nocturnal leg cramps
• Akathisia
• Excessive movement without specific sensory
  complaints
• History of dopamine antagonist use no nighttime
  worsening
• Vascular disease
• Varicose veins
• Sleep disorders
• Sleep apnea or REM behavioral disorder

Earley CJ. N Engl J Med. 20033482103-2109
Garcia-Borreguero D, et al. Acta Neurol Scand.
2004109303-317 Stiasny K, et al. Sleep Med
Rev. 20026253-265.
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RLS Primary Features

• Symptom descriptions
• Creepy, crawly, tingly
• Painful, burning, achy
• Like worms or bugs crawling deep in leg muscle
• Like water running under the skin
• Like soda water in the veins
• Muscle ache or tension
• Compelling urge to move
• Usually affects both legs simultaneously
• Can be unilateral or alternating
• Arms and trunk may become involved
• Many patients experience daily symptoms
• Rest (sitting or lying down) provokes symptom
  onset
• Getting up (activity) can immediately, and at
  least partially, relieve discomfort

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RLS Primary Features (contd)

• Circadian pattern to symptoms
• Peak symptom severity between midnight and 400
  AM
• Often marked relief between 600 AM and 1000 AM
• Persists even in unconventional sleep/wake
  cycles (eg, shift work)
• Frequently associated features
• Involuntary limb movements while patient is awake
• Periodic limb movements (PLM) while patient
  sleeps
• Characterized by periodic episodes of
  repetitive/highly stereotyped limb movements
  episodes of muscle contraction last from 0.5-5
  seconds, interval 20-40 seconds
• Loss of restful sleep contributes to daytime
  sleepiness

Earley CJ. N Engl J Med. 20033482103-2109.
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RLS When to Refer

• Consider referral to neurologist for EMG/NCV
• If peripheral neuropathy is suspected
• Consider referral to sleep center or sleep
  specialist
• In children
• If coexisting obstructive sleep apnea or
  narcolepsy is suspected
• If sleep disturbance continues after treatment

EMG/NCV electromyography/nerve conduction
velocity studies. Earley CJ. N Engl J Med.
20033482103-2109 Parker KP, et al. Nurs Clin
North Am. 200237655-673 Stiasny K, et al.
Sleep Med Rev. 20026253-265.
34
Treatment
35
RLS Treatment Considerations

• Clinical history
• Patients age
• Potential aggravators
• Frequency, severity, and timing of symptoms
• Comorbid conditions

36
RLS Treatment Considerations (contd)

• RLS severity and frequency will vary from
  patient to patient
• Mild, moderate, severe
• Intermittent, frequent, daily, refractory
• Treatment often is individualized
• Need to determine optimal medication or
  combination of medications, dosages, and
  nonpharmacologic treatments

37
RLS Treatment Goals

• Provide adequate restorative sleep that occurs
  at desirable and appropriate times
• Allows relief and/or resolution of daytime
  symptoms (fatigue, lack of concentration,
  sleepiness, and depression)
• Enable patients to enjoy quiet, relaxing, passive
  activities that have evoked symptoms (reading,
  watching television, attending the theater,
  travel by car or plane)

Hening WA. Am J Med. 2007120522-527.
38
RLS Treatment StrategiesNonpharmacologic

• Remove potential aggravators
• Sleep deprivation
• Alcohol
• Exercise (too much vs too little)
• Caffeine
• Smoking
• Consider discontinuing medications that can
  worsen RLS
• SSRIs (eg, paroxetine, fluoxetine, sertraline)
• Tricyclics (eg, amitriptyline, nortriptyline)
• Dopamine antagonists (eg, clozapine, risperidone)
• Antihistamines
• Treat secondary causes
• Iron deficiency
• Renal disease

Hening W, et al. Sleep. 199922970-999 Hening
WA. Am J Med. 2007120522-527 Phillips B, et
al. Arch Intern Med. 20001602137-2141 Stiasny
K, et al. Sleep Med Rev. 20026253-265.
39
RLS Treatment StrategiesNonpharmacologic
(contd)

• Improve sleep hygiene
• Regular bedtime and wake time
• Restrict bed to sleep and intimacy
• Avoid perturbing activities immediately before
  sleep
• Moderate exercise
• Neither daytime inactivity nor unusual and
  excessive exercise
• Reduced nighttime exercise
• Brief walk before bedtime
• Relaxation techniques
• Baths (cold, warm, hot)
• Leg vibration/massage
• Games

Parker KP, Rye DB. Nurs Clin North Am.
200237655-673 Hening W, et al. Sleep.
199922970-999 Hening WA. Am J Med.
2007120522-527 Hu J. J Tradit Chin Med.
200121312-316 Rajaram SS, et al. Sleep Med.
20056101-106.
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RLS Treatment StrategiesSymptom Severity
Intermittent Daily Refractory
Occasional bouts that last for days Bouts during provocative situations (long-duration travel) Can be managed by medications given prn or prophylactically Frequent, especially daily, may require daily medication Initial attempts at daily treatment fail Those who cannot tolerate dopamine agonists (side effects or augmentation) Medication change, dose adjustment, or combination therapy
Hening WA. Am J Med. 2007120522-527.
41
Which agent do you most commonly
prescribe for your patients with RLS?

1. Benzodiazepine
2. Gabapentin
3. Levodopa
4. Pramipexole
5. Ropinirole

Use your keypad to vote now!
42
RLS Treatment Strategies Pharmacologic by
Symptom Severity
Intermittent Daily Refractory
Levodopa with decarboxylase inhibitor (carbidopa or benserazide) Dopamine agonists Pramipexole Ropinirole Change to different dopamine agonist
Mild-to-moderate strength opioid Anticonvulsants Gabapentin Switch to opioid or anticonvulsant
Sedative-hypnotics Opioids Hydrocodone Oxycodone Tramadol Extended-release formulations Add second drug, possibly with reduced agonist dose
Dopamine agonist low dose, if tolerated Benzodiazepines Clonazepam Consider drug holiday may be covered by opioid or different agonist
Dopamine agonist low dose, if tolerated Benzodiazepines Clonazepam High-potency opioids for severe, resistant cases
Hening WA. Am J Med. 2007120522-527.
43
RLS Pharmacologic TherapyDose Ranges of Common
Medications
Dopaminergics Dopaminergics Opioids Opioids
Levodopa 100-200 mg Codeine 15-120 mg
Ropinirole 0.25-6 mg Propoxyphene 65-520 mg
Pramipexole 0.125-1 mg Oxycodone 5-20 mg
Cabergoline 0.5-4 mg Hydrocodone 5-20 mg
Tramadol 50-400 mg
Methadone 5-40 mg
Anticonvulsants Anticonvulsants Sedative-Hypnotics Sedative-Hypnotics
Gabapentin 3002700 mg Clonazepam 0.5-2 mg
Hening WA. Am J Med. 2007120522-527.
44
RLS Treatment Strategies Pharmacologic
Class Drug examples Advantages Disadvantages
Dopaminergics Carbidopa/levodopa Can be used prn Useful for intermittent RLS 80 develop augmentation (with daily therapy) Insomnia, sleepiness, GI problems
Dopaminergics Nonergot-derived Pramipexole,ropinirole Ergot-derived Cabergoline Useful in moderate-to-severe RLS High efficacy Sleepiness Nauseaincrease dose slowly
FDA-approved agents for treatment of RLS. GI
gastrointestinal. Earley CJ. N Engl J Med.
20033482103-2109 Quilici S, et al. Sleep Med.
2008 Jan 26 Epub Stiasny K, et al. Sleep Med
Rev. 20026253-265.
45
TREAT RLS US Ropinirole Efficacy
Mean IRLS Rating Scale Total Score at Each Visit
25
Week 12 LOCF P lt.0001
20

IRLS Rating Scale Total Score (mean)
15
Placebo (n 193)

10








5
Ropinirole (n 187)
0
Baseline
Day 3
Week 1
Week 2
Week 3
Week 4
Week 5
Week 6
Week 8
Week 10
Week 12
Time Point (OC)
P .003. P lt.001.
A decrease in score denotes improvement
IRLS International Restless Legs Syndrome LOCF
Last observation carried forward OC observed
case. Data on file, GlaxoSmithKline (TREAT RLS
US).
46
Pramipexole Efficacy
Total IRLS Score
P lt.0001 P .00001
Adjusted Mean Change From Baseline
n 21
n 86
n 114
n 224
n 85
n 254
Partinen M, et al. Poster presented at Second
World Congress of the World Association of Sleep
Medicine. February 4-8, 2007 Oertel WH, et al.
Pramipexole RLS Study Group. Mov Disord.
200722213-219 Winkelman JW, et al. Neurology.
2006671034-1039.
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RLS Treatment Strategies Pharmacologic
Class Drug Examples Advantages Disadvantages
Opioids Codeine, hydrocodone, tramadol Useful for intermittent and daily RLS Constipation, sleepiness, cognitive changes Tolerance, dependence
Benzodiazepines Clonazepam, temazepam Helpful in some patients when other agents are not tolerated May improve sleep Daytime sleepiness and cognitive impairment
Anticonvulsants Carbamazepine, gabapentin Consider when dopamine agonists fail Helpful in patients with neuropathy, pain GI disturbance, nausea, sedation, dizziness
Iron Ferrous sulfate, IV iron dextran Use in patients if serum ferritin lt50 µg/dL
None of the agents presented on this slide are
FDA approved for RLS. Earley CJ. N Engl J Med.
20033482103-2109 Stiasny K, et al. Sleep Med
Rev. 20026253-265.
48
RLS Pharmacologic ManagementClinical
Considerations

• Evidence-based and clinical guidelines identify
  dopamine agonists as a first-line treatment for
  RLS
• Start with lowest medication dose and slowly
  increase to effective dose
• Start dose at bedtime
• If necessary, add an evening dose then tailor to
  patients symptoms
• Watch for augmentation and rebound

Littner M, et al. Sleep. 200427557-559.
49
Augmentation and Rebound

• Augmentation
• Defined by a combination of earlier onset of RLS
  symptoms, increase of symptom severity, and
  involvement of other limbs
• Time shift of symptoms from bedtime to early
  evening, then to daytime
• Seen in up to 82 of patients with RLS receiving
  levodopa
• Rebound
• Wearing off of drug effect, typically in the
  morning
• Seen in up to 25 of RLS patients receiving
  levodopa

Allen RP, Earley CJ. J Clin Neurophysiol.
200118128-147 Allen RP, Earley CJ. Sleep.
199619205-213 Guilleminault C, et al.
Neurology. 199343445.
50
Iron-Deficiency RLS Treatment

• Consider if serum ferritin lt50 µg/Lor iron
  saturation lt16
• Ferrous gluconate
• 325 mg 100 mg vitamin C 1-3x/d on an empty
  stomach
• Vitamin C improves absorption
• May take significant length of time for benefit
• Iron dextran (IV) is an option for patients with
  a proven iron deficiency
• Single 1-g iron infusion

Davis BJ , et al. Eur Neurol. 20004370-75
Earley CJ. N Engl J Med. 20033482103-2109
Earley CJ, et al. Sleep Med. 20045231-235.
51
Case Study
52
A 45-Year-Old Woman Comesfor Routine Examination

• A 45-year-old woman comes to your office for
  routine examination
• She complains of increasing difficulty sleeping,
  discomfort in her legs in bed at night, and
  feeling tired at work
• She suffers from depression and has been taking
  venlafaxine 45 mg/d for the past year
• She has rheumatoid arthritis controlled by
  treatment with celecoxib 200 mg BID
• Shes a nonsmoker drinks 4-5 cups of coffee
  daily drinks alcohol only socially

53
Which of the following is consistent with a
diagnosis of RLS?

1. Family history of similar sleep symptoms
2. Iron deficiency anemia
3. Rheumatoid arthritis
4. Treatment of depression
5. All of the above

Use your keypad to vote now!
54
Patient History and Symptoms

• You question the patient about her family
  history, symptoms, and sleep patterns
• She reports
• My mom used to complain that my father couldnt
  sit still on a plane or at the movies. And he
  would keep her up at night with his jerking
  legs.
• She says,
• When I get the creepy, crawlies in my legs, I
  have to get up and move.
• Sensation is moderately painful
• She reports she has symptoms nearly every night
  when she watches TV in bed

55
Physical Examination

• Physical examination is normal with the presence
  of some joint pain in the fingers of the right
  hand
• You order laboratory tests

56
Which of the following is the most helpful in
diagnosing suspected RLS?

1. A1C
2. CBC
3. Chemistries (BUN/creatinine ratio)
4. Folate
5. Serum ferritin

Use your keypad to vote now!
57
Evaluation and ExaminationResults

• Clinical history
• Sleep disturbance and discomfort in her legs at
  night
• Patients age
• Slightly younger than average for RLS
  presentation
• Potential aggravators
• Poor sleep hygiene, caffeine use, antidepressant
  use
• Frequency, severity, and timing of symptoms
• Nearly daily, moderately severe, occurs only at
  night
• Comorbid conditions
• Depression, rheumatoid arthritis, iron-deficiency
  anemia (?)

58
Before the patient leaves the office and before
laboratory results are back, you

1. Change her antidepressant to bupropion
2. Counsel her on sleep hygiene
3. Prescribe a dopaminergic medication
4. Prescribe an NSAID with a PM formulation
5. Prescribe a sleep medication

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59
Follow-Up 1 Week Later

• Patients laboratory results
• Negative for diabetes, renal impairment,
  infections
• Serum ferritin 33 ng/mL
• You call the patient with the lab results
• She says her symptoms are unchanged

60
What is the next step?

1. Prescribe a different antidepressant
2. Prescribe a dopaminergic
3. Start an anticonvulsant
4. Add oral iron
5. Refer to a neurologist

61
Treatment

• A diagnosis of RLS was made based on typical
  symptoms of leg discomfort contributing to
  nocturnal restlessness
• Patient was given ferrous gluconate 325 mg TID
  vitamin C 100 mg TID
• Ropinirole 0.25 mg/d was initiated and increased
  every 5 days to a maximum of 2
  mg/night
• Due to nausea and vomiting from ropinirole,
  medication changed to pramipexole 0.125 mg, then
  increased to 0.5 mg
• Her iron deficiency anemia responded to oral
  iron,
• but leg symptoms persisted during the night

62
Treatment (contd)

• Venlafaxine was changed to bupropion her leg
  symptoms and restlessness improved
• Diagnosis of RLS aggravated by venlafaxine was
  made
• Pramipexole was gradually reduced to 0.125 mg,
  but her symptoms returned

63
At this point, what would you do?

1. Add clonazepam
2. Add an opioid
3. Change to another dopaminergic medication
4. Increase pramipexole
5. Restart venlafaxine

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64
Internet Resources

• The Restless Legs Syndrome Foundation
• www.rls.org
• National Institute of Neurological Disorders and
  Stroke
• www.ninds.nih.gov/disorders/restless_legs
• National Sleep Foundation
• www.sleepfoundation.org
• WEMOVETM
• www.wemove.org
• PubMed
• www.ncbi.nlm.nih.gov/PubMed/

65
Q A
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66
PCE Takeaways
66
67
PCE Takeaways

• RLS can be diagnosed easily by primary care
  clinicians with simple diagnostic questions
• Ask patients about sleep
• Remember URGE
• RLS treatment should include removing
  potential aggravators
• RLS treatment should be individualized and
  include nonpharmacologic and pharmacologic
  interventions
• Evidence-based and clinical guidelines identify
  dopamine agonists as a first-line pharmacologic
  treatment for RLS

67
68
Based on the clinical data presented, how likely
is it that the prevalence of RLS in your
practice is greater than previously thought?

1. Very likely
2. Likely
3. Somewhat likely
4. Not likely

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69
2008
Symposia Series 1

• Stamford Marriott
• Stamford, Connecticut
• April 26, 2008

69
69