Managing your RLS with Medication

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Some people have no choice but to take medication to manage their RLS. This page provides guidance of some of the medications which are available to ease your RLS and is based on current international best practice as defined in the Mayo Algorithm and updated in recent AASM guidance.

You should always speak to your doctor about medication. Please be aware that UK medical practice for RLS is somewhat outdated and the treatments described may not always be immediately or easily available.

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SUMMARY

• Iron status should be assessed in all patients with RLS and appropriate oral or intravenous iron therapy considered.

• Unless contraindicated, alpha2-delta ligands are first-line agents for treatment of chronic persistent RLS

• Low-dose opioid therapy is indicated for the management of refractory RLS with appropriate precautions or where alpha-2-delta ligands are not well tolerated for chronic persistent RLS

• Dopamine agonists can be effective initially but due to significant potential side effects are generally reserved for specific circumstances such as end of life treatment
   

• Other medications such as levodopa and benzodiazepines can be helpful for intermittent RLS but come with side effects which normally make them unsuitable for chronic persistent RLS or long term use

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IRON THERAPY – SUPPLEMENTS AND INFUSIONS

Clinical research indicates that patients with RLS may have lower than normal iron stores in the brain and that iron therapy can be beneficial even if patients are not considered anaemic by normal standards. A ferritin level of 100µg/L is generally regarded as the minimum for RLS sufferers with some seeing benefits from levels up to 200-300µg/L.

Some people see immediate improvement from daily oral iron supplements while others benefit from incrementally raising the level of iron stores over time, measured by the concentration of ferritin in the blood via a blood test.  

If oral supplements fail to raise ferritin level then intravenous infusions can be effective although these are not routinely available from the NHS for RLS. 

In one study 60% of people with RLS benefitted from iron supplementation. 

Click here for our one page guide to Iron Therapy.

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ALPHA-2 DELTA LIGANDS – PREGABALIN AND GABAPENTIN

Also known as gabapentinoids, this a class of drug which includes pregabalin and gabapentin and is used to treat epilepsy, neuropathic pain and anxiety, and can be used off label as a first line treatment for chronic persistent or refractory RLS. NICE Clinical Knowledge Services recommends alpha-2 delta ligands as a first line drug option.

Pregabalin and gabapentin are very similar in effect although some people find one to be more effective than the other and similarly may experience fewer side effects on one than the other.

Gabapentin doses are typically 6 times larger than pregabalin for the same benefit.

Gabapentin and pregabalin are usually administered in the evening to maximise their effect when RLS symptoms are worse. 

Gabapentin is not easily absorbed above 600mg so split doses two hours apart may be required to enhance absorption and efficiency.  Magnesium supplements can affect absorption and are best taken two hours before gabapentin. 

Gabapentin should be started at 300mg (100mg for over 65) and increased every few days until symptoms are relieved. The normal effective dose is 1200-1800mg.

Pregabalin is more easily absorbed and can be taken in one dose. Starting dose is 75mg (50mg for over 65) and the average effective dose is 150-200mg. 

Gabapentin and pregabalin can take up to 3 weeks to become fully effective. Common side effects of drowsiness, dizziness, unsteadiness, oedema and weight gain usually resolve after 6 to 8 weeks.

Side effects can include depression and suicidal ideation and should be monitored, especially at higher doses.

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LOW DOSE OPIOIDS – BUPRENORPHINE, TRAMADOL AND OXYCODONE

For refractory RLS, where first line treatments have failed due to adverse effects or augmentation, low dose opioids can be highly effective and do not generally lead to addiction or tolerance if patients are adequately screened and monitored.

The Massachusetts General Hospital Opioid Study shows that low dose opioids used in RLS do not lead to an increase in dose over long periods of time. (National RLS Opioid Registry massgeneral.org). Opioids should not be withheld due to fear of tolerance or dependence as they can result in complete resolution of refractory RLS and improved quality of life.

in the UK, Oxycodone is licensed for RLS, but codeine, tramadol and buprenorphine can be prescribed off licence. Most general practitioners may be reluctant to prescribe opioids without the supervision of a neurologist.

Tramadol is the only opioid that can cause augmentation and worsening of symptoms should be monitored.

Common side effects of nausea, skin itching, sweating and anxiety should be monitored and treated accordingly.

Low dose opioids can also be used for intermittent or occasional RLS where side effects may be less of an issue.

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DOPAMINE AGONISTS – PRAMIPEXOLE, ROPINIROLE AND ROTIGOTINE

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Dopamine agonists,  mainly used in the treatment of Parkinson’s disease, are no longer first line treatment for RLS amongst experts due to the high risk of augmentation (drug induced worsening of RLS) and impulse control disorders. While initially very effective, many people find RLS symptoms return after a period of time requiring an increase in dosage. This may recur over time with the increased dose often causing symptoms to extend to other times of the day and other parts of the body e.g. trunk, arms and neck.

Impulse control disorders such as gambling, hypersexuality, compulsive shopping and binge eating are a significant risk from dopamine agonists.

If you are on any of these medications, you should arrange a review with your doctor to discuss augmentation and, if the drug has lost effectiveness, to discuss a slow taper and a switch to another medication in another class of drugs. Withdrawal from dopamine agonists can be very difficult and traumatic and will require careful monitoring.

Click here for our one page guide to withdrawal from dopamine agonists.

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OTHER MEDICATIONS – LEVODOPA, BENZODIAZEPINES AND DIPYRIDAMOLE

Other medications can have beneficial effects for RLS although due to significant side effects or limited evidence they are not generally used for chronic or persistent RLS. However for intermittent or occasional RLS the side effects may be manageable.

Carbidopa Levodopa is a dopaminergic drug and should be used with caution due to the high rate of augmentation (drug induced worsening of RLS) which occurs in up to 70% of patients taking it on a daily basis. For this reason, it should be prescribed only for intermittent use.

Benzodiazepines (diazepam, lorazepam, temazepam, clonazepam) before sleep may be useful for occasional RLS but longer lasting agents, like clonazepam, may result in more adverse effects such as unsteadiness in the night and daytime drowsiness and cognitive impairment.

Dipyridamole was trialled in a 2 week study in 2021 and was shown to have benefits for RLS symptoms. It was given a conditional recommendation in the recent AASM guidance but is not widely prescribed. Some patients have experienced significant side effects such as headaches.

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COMMONLY PRESCRIBED RLS MEDICATIONS
Some of the most frequently prescribed RLS medications are listed below, accompanied by details of the recommended starting, average and maximum daily dosage, and the expected half-life of the drug (how long a drug takes to lose half its strength).

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Please note that the following is an overview and does not capture every medication used to treat RLS. You may also find that the amount you are prescribed differs from the doses suggested below. These details are for information only but we hope they will help you in making informed decisions with your GP.

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MEDICATIONS TABLE - see downloadable and printable pdf below

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