What medication can be given to a patient with restless leg syndrome (RLS) symptoms?

Treatment of Restless Leg Syndrome in Hospitalized Patients

Alpha-2-delta ligands (gabapentin, gabapentin enacarbil, or pregabalin) should be the first-line pharmacological treatment for hospitalized patients with RLS symptoms, as they are strongly recommended by the American Academy of Sleep Medicine with moderate certainty of evidence and carry lower risk of long-term complications compared to dopaminergic agents. 1, 2, 3

Initial Assessment Before Starting Medication

Before initiating any pharmacological treatment, check morning fasting iron studies including serum ferritin and transferrin saturation 2, 4:

• If ferritin ≤75 ng/mL or transferrin saturation <20%, start iron supplementation immediately 1, 2, 3
• IV ferric carboxymaltose is strongly recommended for rapid correction in hospitalized patients who meet these iron parameters 2, 3
• Oral ferrous sulfate is an alternative option but works more slowly 1, 3

Review and discontinue medications that may worsen RLS 2, 3:

• Antihistamines (including diphenhydramine commonly used for sleep in hospitals) 2, 3
• Serotonergic antidepressants (SSRIs, SNRIs) 2, 3
• Antidopaminergic medications (metoclopramide, prochlorperazine) 2, 3

First-Line Pharmacological Treatment: Alpha-2-Delta Ligands

Gabapentin dosing for hospitalized patients 2, 4:

• Start at 300 mg three times daily (900 mg/day total) 2
• Titrate by 300 mg/day every 3-7 days until reaching maintenance dose of 1800-2400 mg/day divided three times daily 2
• Doses up to 3600 mg/day are well-tolerated in clinical studies 2
• Common side effects include somnolence and dizziness, which are typically transient and mild 2

Pregabalin as an alternative 2, 3, 4:

• Allows twice-daily dosing with potentially superior bioavailability compared to gabapentin 2
• Strongly recommended as first-line therapy with moderate certainty of evidence 3

Why Dopamine Agonists Should Be Avoided

The American Academy of Sleep Medicine suggests against the standard use of dopamine agonists (pramipexole, ropinirole, rotigotine) due to the significant risk of augmentation with long-term use 1, 2, 3:

• Augmentation is characterized by earlier onset of symptoms during the day, increased symptom intensity, and spread of symptoms to other body parts 2
• Ropinirole specifically receives a conditional recommendation against standard use with moderate certainty of evidence 1
• Pramipexole also receives a conditional recommendation against standard use with moderate certainty of evidence 1, 2
• These agents may only be considered for short-term use in patients who place higher value on immediate symptom relief and lower value on long-term adverse effects 1

Additional concerns with dopamine agonists in hospitalized patients 5:

• Syncope occurs in 12% of patients with early Parkinson's disease on ropinirole vs 1% on placebo 5
• Orthostatic hypotension and falls are common, particularly dangerous in hospitalized patients 5
• Hallucinations and psychotic-like behavior can occur, especially in elderly patients 5
• Impulse control disorders including compulsive gambling and shopping 2
• Nausea occurs in 40% of RLS patients on ropinirole vs 8% on placebo 5

Medications Specifically Recommended Against

The American Academy of Sleep Medicine recommends against the following 1, 3:

• Cabergoline (strong recommendation against use) 1
• Bupropion (conditional recommendation against) 1
• Carbamazepine (conditional recommendation against) 1
• Clonazepam (conditional recommendation against) 1
• Valproic acid (conditional recommendation against) 1

Alternative Options for Refractory Cases

If alpha-2-delta ligands are ineffective or poorly tolerated 2, 3:

• Extended-release oxycodone and other low-dose opioids are conditionally recommended for moderate to severe refractory cases 2, 3
• Opioids are particularly effective for treating augmentation when transitioning off dopamine agonists 6, 7
• When monitored appropriately, opioids can be safe and durable for long-term therapy 7
• Evidence shows relatively low risks of abuse and overdose in appropriately screened patients, with only small dose increases over 2-10 years 2

Critical Pitfalls to Avoid

Do not use single nighttime dosing of gabapentin 2:

• Single nighttime dosing fails to address daytime RLS symptoms and provides suboptimal 24-hour coverage 2
• Three-times-daily dosing is necessary for adequate symptom control 2

Do not start dopamine agonists as first-line therapy 1, 2, 3:

• Despite their historical use and effectiveness for short-term symptom relief 8, 9, 10, the risk of augmentation makes them inappropriate for standard use 1, 2
• If a patient is already on a dopamine agonist, do not abruptly discontinue it as this causes profound rebound RLS and insomnia 6
• Instead, add an alpha-2-delta ligand or opioid first, then slowly taper the dopamine agonist 6

Address iron deficiency even if ferritin appears "normal" 2, 3:

• RLS patients require higher ferritin targets (≥75 ng/mL) than the general population because brain iron deficiency plays a key role in pathophysiology 2
• Standard "normal" ferritin ranges are insufficient for neurological function in RLS 2