A 10-year, longitudinal assessment of dopamine agonists and methadone in the treatment of restless legs syndrome – Source: Sleep Medicine, Jan 14, 2011

Background: Restless legs syndrome (RLS) is a chronic disease, which is managed with palliative medications that are likely to be required for a patient's lifetime. It is, therefore, important to know the long-term consequences of these treatments.

Currently, the most commonly prescribed treatment for RLS is one of the dopamine (DA) agonists. Most of what we understand about efficacy and side effects of the DA agonists are, however, derived from relatively short-term studies.

This is particularly a problem since these medications produce in some patients a significant increase or augmentation of RLS symptoms known to occur during the first 2 years of treatment and perhaps even later in treatment.

The primary aim of this study was to determine the long-term efficacy (10-year) for commonly used RLS medication types: dopaminergic agonists and opioids.

Methods: Records of all RLS patients treated in one tertiary care center with:

Pramipexole [aka Mirapex and other brand names, a “non-ergoline-based” dopamine agonist also used for early Parkinson’s and experimentally for cluster headache, depression, and fibromyalgia],

Pergolide [aka Permax and other brand names, an ergoline-based dopamine agonist also used in some countries to treat Parkinson’s and by veterinarians for some conditions in animals; withdrawn from the US market in 2007]

• Or methadone [aka Symoron and scores of other brand names, a synthetic opioid also used as an anti-addictive for patients on opioids, for pain, and as a cough suppressant]

…. during the years 1997-2007 were reviewed.

The duration and reason for any discontinuation of treatment and medication doses were recorded.

Annual rates for discontinuing treatment persisted for up to 10 years of treatment and were fairly constant after the first year at:

• 9% for pramipexole,

• 8% for pergolide,

• And 0% for methadone.

Similarly, annual augmentation [symptom worsening] rates were fairly constant after the first year and persisted for up to 10 years at:

• 7% for pramipexole,

• 5% for pergolide,

• And 0% for methadone.

The percentage continuing on the treatment medication for over 5 years was 58% for pramipexole and 35% for pergolide.


The DA agonists appear to have a limited period of clinical utility for many patients.

Severe augmentation, while not common in any 1 year, can develop even after years on the medication.

Methadone, in contrast, shows neither augmentation nor major problems with continued efficacy after the first year of treatment.

[Note: Another type of drug – gabapentin, aka Neurontin – may improve RLS symptoms according to a recent 52-week trial, but long term results are not known. Gapapentin is an anticonvulsive GABA analog drug used to treat post-shingles nerve pain and depression.]

Source: Sleep Medicine, Jan 14, 2011. PMID: 21239226, by Silver N, Allen RP, Senerth J, Earley CJ. Johns Hopkins University, Dept. of Psychology and Brain Sciences, 3400 N Charles St., Baltimore, Maryland, USA.

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