Restless Legs
Overview
Restless leg syndrome is a neurological sensorimotor disease. It is a common and troubling symptom for patients with kidney disease, especially advanced chronic kidney disease. It causes an urge to move legs at rest and a disruption of sleep which can negatively impact a person’s quality of life. Restless leg syndrome might be influenced by genetic, environmental and medical factors.
- Even if your patient does not have Kidney Disease consider using the ESAS-r:Renal to assess the severity of the symptoms as well as other concomitant symptoms
The International Restless Leg Syndrome Study Group (IRLSSG) has developed five criteria that help to diagnose restless leg syndrome:
- An urge to move the legs usually but not always accompanied by or felt to be caused by uncomfortable and unpleasant sensations in the legs
- The urge to move the legs and any accompanying unpleasant sensations begin or worsen during periods of rest or inactivity such as lying down or sitting
- The urge to move the legs and any accompanying unpleasant sensations are partially or totally relieved by movement, such as walking or stretching, at least as long as the activity continues
- The urge to move the legs and any accompanying unpleasant sensations during rest or inactivity only occur or are worse in the evening or night than during the day
- The occurrence of the above features is not solely accounted for as symptoms primary to another medical or a behavioral condition (e.g. myalgia, venous stasis, leg edema, arthritis, leg cramps, positional discomfort, habitual foot tapping)
- Correct anemia and iron deficiency
- Correct hyperphosphatemia
- Remove drugs which may contribute to or cause restless leg syndrome
- Dopamine antagonists:
- antipsychotics: pimozide, haloperidol (Haldol), olanzapine (Zyprexa), risperidone, quetiapine (Seroquel), methotrimeprazine (Nozinan)
- other: metoclopramide (Metonia), promethazine
- Antidepressants
- Mirtazapine (Remeron)
- SSRIs: e.g. citalopram, escitalopram, fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft)
- SNRIs: e.g. duloxetine (Cymbalta), venlafaxine (Effexor)
- Others: TCA’s, carbamazepine (Tegretol), lithium, calcium channel blockers; opioids may also exacerbate RLS in this population
- Antihistamines
- Mostly 1st generation like diphenhydramine, chlorpheniramine maleate
- Lithium
- Dopamine antagonists:
Encourage the following behaviour:
- Limit/avoid stimulants such as alcohol, caffeine and nicotine
- A trial of mental alerting activities, such as video games or crossword puzzles, to reduce symptoms at times of boredom
- The promotion of good sleep hygiene:
- Wake up at the same time every morning
- Try not to go to bed until you feel sleepy
- Do not “try” to fall asleep
- Limit/avoid napping during the day
- Limit/avoid caffeine in the evening
- Save your bedroom for sleep (and sex) only
- Incorporate relaxation techniques
- If realistic for the patient, aerobic exercise, walking, and/or stretching
If the patient continues to report restless leg syndrome that impairs quality of life, consider pharmacological options
Gabapentin First-line Agent
- Starting dose 300 mg, orally at night
- Titrate to tolerance and effect
- Maximum dose: 1.2 g nightly
- Dose adjustment for kidney disease: Start at 100 mg orally at night. Titrate slowly to tolerance and effect; suggest 100 mg every 5-7 days
- Recommended maximum dose in patients with:
- Crcl ≤ 15 ml/min: 300 mg/day administered once daily
- CrCl > 15-29 ml/min: 700 mg/day administered once daily
- CrCl > 30-59 ml/min, 1400 mg/day; should be divided by 2 and administered twice daily (BID)
- Extended release not recommended if CrCl < 30 ml/min
- Dose adjustment for liver disease: Start at 100 mg orally at night. Titrate slowly to tolerance and effect; suggest 100 mg every 5-7 days. Dose adjust with kidney dysfunction
- Recommended maximum dose in patients with:
- Crcl ≤ 15 ml/min: 300 mg/day
- CrCl > 15-30 ml/min: 600 mg/day
- CrCl > 30-59 ml/min: 1200 mg/day
- Extended release not recommended if CrCl < 30 ml/min
Contraindicated in patients with uncontrolled hepatic encephalopathy
May be associated with increased risk of peripheral edema
Use with caution in patients with Myasthenia gravis, kidney disease, heart failure, seizure disorder, and with history of substance use
Monitor for the common adverse effects of dizziness, impaired coordination, sleepiness/somnolence, confusion and possibly peripheral edema
- It should be taken 2-3 hours before bedtime due to delay of peak onset
Pregabalin First-line Agent
Usual dose 150 to 450 mg per day
- Dose adjustment for kidney disease: Starting dose 25 mg orally at night. Titrate to tolerance and effect every 1 week
- CrCl 30-60ml/min: 300mg per day divided in 2 or 3 doses
- CrCl 15-30ml/min: 150mg per day administered in one or 2 divided doses
- CrCl <15ml/min: 75mg per day administered once daily
- Extended release is not recommended
- Dose adjustment for liver disease: Starting dose is 25-50 mg orally at night. Titrate to tolerance and effect every 1 week. Dose adjust with kidney dysfunction
- Recommended maximum dose in patients with Crcl < 45 ml/min: 75 mg at night (immediate release)
- Extended release is not recommended
Contraindicated in patients with uncontrolled hepatic encephalopathy
Use with caution in patients with Myasthenia gravis, kidney or liver failure, seizure disorder, and with history of substance use
Use with caution when used with opioids - it may increase the risk of serious side effects and opioid overdose
Concomitant use with opioids may result in respiratory depression, profound sedation, syncope, and death
- Do not discontinue abruptly. When discontinued, their doses should be tapered over 1-2 weeks
- Do not discontinue abruptly. When discontinued, their doses should be tapered over 1-2 weeks
- It should be taken 1-2 hours before bedtime due to delay of onset
Pramipexole (Mirapex) First-line Agent
- Starting dose is: 0.125 mg PO 2 hours prior to sleep
- Titrated by 0.125 mg PO every 7 days
- Maximum dose: 0.75 mg/day
Contraindicated in patients with active psychosis and heart failure
Use with caution in patients with dyskinesia, impulse control disorder, neuroleptic malignant syndrome, orthostatic hypotension, history of mental illness like psychosis, and somnolence. Clearance is decreased in sever renal impairment, elderly and in women
- Clearance is decreased in severe renal impairment, (75% lower CrCl ~20 mL/min)
- The half-life increases approximately 40% and clearance decreases approximately 30% in patients 65 + years and in women
Rotigotine (Neupro) First-line Agent
- Transdermal patch 1 mg/24 hr applied once daily
- Titrated by 1 mg/24 h weekly
- Maximum dose: 3 mg/24 hr
Contraindicated in patients with active psychosis
Use with caution in patients with heart failure, fluid retention, fibrosis, history of illness like psychosis, impulse control disorder, orthostatic hypotension, and somnolence
- Requires tapering if discontinuing. Avoid abrupt withdrawal
- It should be taken 2-3 hours before bedtime due to delay of peak onset
- Half life after removing the patch is 5 to 7 hours; time to peak plasma 15 to 18 hours
Ropinirole (Requip) First-line Agent
- Starting dose is: 0.25 mg PO 2 hours prior to sleep
- Titrated by 0.25 mg PO every 5-7 days
- Maximum dose: 4 mg/day
Contraindicated in patients with active psychosis
Use with caution in patients with heart failure, dyskinesia, impulse control disorder, neuroleptic malignant syndrome, orthostatic hypotension, history of mental illness like psychosis, and somnolence
- It should be taken 2-3 hours before bedtime due to delay of peak onset
- Taper gradually when discontinuing therapy