Medline ® Abstracts for References 32,65

OBJECTIVE: Few studies have examined the long-term use of dopamine agonists for restless legs syndrome (RLS). We report a cohort study of 50 patients initially prescribed pramipexole between 1998 and 2002. The objective was to determine duration of treatment, long-term efficacy, development of side effects and augmentation over an extended period.

METHODS: We performed a long-term analysis on a previously reported group of patients initially followed for a mean of 27.2 months. Data were collected using retrospective chart reviews, written surveys and systematic telephone interviews.

RESULTS: Pramipexole was used for a mean of 8 years (range 0.6-12 years). Nine (18%) discontinued pramipexole because of poor efficacy (four), impulse control disorders (ICD) (two), augmentation (one) and resolved symptoms (two). Pramipexole was reported completely effective in 40% (compared to 67% at the end of the initial study), partially effective in 58% and ineffective in 2%. The median daily dose increased from 0.38 mg after initial stabilization to 1.0mg at the end of the study. As many as 74% of patients experienced side effects. A totalof 56% reported daytime sleepiness including 10% reporting sleep attacks while driving and 10% developed ICDs. Augmentation developed in 42% of patients, after a mean of 16.5 months, and no later than 4.1 years after commencing treatment. A total of 28% needed additional non-dopaminergic medications.

CONCLUSION: The efficacy of pramipexole dropped with time, with increase in dose and addition of other agents, although the majority of patients remained on the drug. Problems included the development of augmentation within the first 4 years of therapy and side effects such as sleepiness increasing with time and the development of ICDs. The study highlights the need for further research into alternative non-dopaminergic treatments for RLS.

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, pergolide or methadone during the years 1997-2007 were reviewed. The duration and reason for any discontinuation of treatment and medication doses were recorded.

RESULTS: 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 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.

CONCLUSIONS: 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.