Table 1

Commonly used medications in restless legs syndrome

Medication	Minimum starting dose	Effective dose range	Augmentation	FDA/EMA approved for RLS	Comments
Gabapentin	100–300 mg/day	300–2400 mg/day	Unknown	Not approved	No RCTs due to its pharmacokinetic limitations. Need to be taken 2–3 hours before symptom onset. Improves sleep initiation and sleep maintenance May need multiple doses AE: drowsiness, dizziness, oedema
Gabapentin enacarbil	Age <65 years 600 mg Age >65 start 300 mg	300–1200 mg day	Unknown	FDA approved	RCT shows benefit in RLS Slow-release gabapentin prodrug Not available in UK Addresses the pharmacokinetic limitations of gabapentin Taken with food Need to be taken 2–3 hours before symptom onset Costly AE: drowsiness, dizziness, oedema
Pregabalin	50–75 mg /day	75–450 mg day	No	Not approved	RCT shows benefit in RLS AE: dizziness, daytime sleepiness suicidal ideation, abuse and weight gain
Ropinirole	0.25 mg/day	0.25–4 mg/day	Yes	Approved	Used as first line therapy Maximum recommended dose for RLS is 4 mg Better PLMS reduction Need to be taken 1–3 hours before symptom onset AE: nausea, somnolence, fatigue, headache, augmentation, impulse control disorders, hypotension
Pramipexole	0.125 mg/day	0.125–0.75 mg/day	Yes	Approved	Used as first-line therapy Maximum recommended dose for RLS is 0.75 mg Need to be taken 1–3 hours before symptom onset Better PLMS reduction AE: nausea, somnolence, fatigue, headache, augmentation, impulse control disorders, hypotension
Rotigotine patch	1 mg/24 hours	1–3 mg/24 hours	Yes	Approved	Used as first-line therapy Maximum recommended dose for RLS is 3 mg/24 hours Need to be taken 1–3 hours before symptom onset AE: reactions at application site, nausea, fatigue, somnolence, headache, augmentation, impulse control disorders, hypotension
Levodopa/carbidopa Levodopa/benserazide	25/100 mg tab ½–1 tab	25/100 mg tab 1–3 tabs	Yes	Not approved	Used for intermittent RLS No longer recommended for long-term therapy due to high risk of augmentation AE: nausea
Codeine	15–30 mg/day	15–30–120 mg/day	Unknown	Not approved	Addiction and dependency relatively uncommon AE: constipation, nausea, somnolence, fatigue, headache, addictive behaviour
Oxycodone/naloxone prolonged release	5 mg oxycodone–2.5 mg naloxone twice daily	10 mg oxycodone–5 mg naloxone to 20 mg oxycodone–10 mg naloxone twice daily	Unknown	Approved by EMS for second line therapy	Addiction and dependency relatively uncommon AE: constipation, nausea, somnolence, fatigue, headache, addictive behaviour
Hydrocodone	5–10 mg/day	20–30 mg/day	Unknown	Not approved	Addiction and dependency relatively uncommon AE: constipation, nausea, somnolence, fatigue, headache, addictive behaviour
Methadone	5–10 mg/day	10–40 mg/day	Unknown	Not approved	Addiction and dependency relatively uncommon AE: constipation, nausea, somnolence, fatigue, headache
Clonazepam	0.25 mg/day	0.25 mg/day 2 mg/day	Unknown	Not approved	Few clinical trails and evidence is lacking
Ferrous sulfate	325 mg daily with 200 mg of vitamin C	325 mg 1 tab twice a day with 200 mg tab vitamin C	Unknown	Not approved	Recommended for ferritin <75 µg/L or iron binding saturation <20% Very poorly absorbed Best on empty stomach AE: constipation, diarrhoea, bloating
IV ferric carboxymaltose	500 mg	500 mg given twice 5 days apart likely improves RLS	Unknown	Not approved	Potentially life-threatening allergic reactions
Iron sucrose	200 mg	400–1000 mg four or five times	Unknown	Not approved	Potentially life-threatening allergic reactions

AE, adverse effects; EMA, European Medicines Agency; FDA, Food and Drug Administration; PLMS, periodic limb movement of sleep; RCT, randomised controlled trial; RLS, restless legs syndrome.