The dopamine agonist pramipexole allays the symptoms of primary restless leg syndrome and improves patients’ sleep quality, at least in the short-term, according to a meta-analysis of randomized, double-blind, placebo-controlled clinical trials.
The mean change in restless leg syndrome (RLS) symptoms assessed using the International RLS Study Group Rating Scale (IRLS) was –5.96, compared with placebo (P less than .00001). The mean change in sleep quality assessed by a variety of patient assessment scales was -0.48 (P less than .00001).
RLS can be categorized as primary or secondary, with the latter due to a variety of causes such as pregnancy, uremia, iron deficiency, anemia, or Parkinson’s disease. Managing those conditions effectively may subsequently improve or even cure RLS.
Primary RLS, however, is defined as that due to no other known cause, and it affects between 1.9% and 4.6% of the European and North American adult populations (Sleep Med. Rev. 2012;16:283-95).
Treatments for the condition include lifestyle changes and medications such as pramipexole and other dopamine agonists, levodopa, and painkillers. Results with dopamine agonists to date have been modest.
"Pramipexole has been proven to be a first-line drug for the treatment of movement disorders such as Parkinson’s disease and RLS," observe Dr. Wei Zhang and associates, who undertook the meta-analysis.
The researchers, who are based at the Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China, added that European guidelines state that pramipexole is effective at providing short-term relief but are less certain on the long-term benefits.
"We conducted a meta-analysis in order to summarize the efficacy and tolerability of pramipexole for the treatment of primary RLS," they explained (Neuropsychiatr. Dis. Treat. 2013;9:1035-43).
Six trials published between 2006 and 2012 were identified that met the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement criteria and had used the IRLS as a primary outcome measure.
Altogether, this included 1,506 patients, 961 of who had received the active treatment. Treatment with pramipexole or placebo lasted for between 3 and 12 weeks, with four trials using flexible and two fixed dosing schedules (0.125, 0.25, 0.5, or 0.75 mg/day).
Pramipexole-treated patients were more likely to be identified as IRLS responders (greater than or equal to a 50% reduction in total scores from baseline) than were the patients given placebo (odds ratio = 2.51). Clinicians and patients were also more likely to report higher response rates ("much" or "very much" improved) with the active therapy, with respective odds ratios of 3.13 (P less than .00001) and 2.80 (P = .05).
Pramipexole was well tolerated in patients with primary RLS, the authors say. As expected, nausea and fatigue were the most common adverse events experienced, with respective relative risks of 2.68 (P less than .001) and 1.82 (P = .013) comparing active with placebo treatment.
There were no differences in the incidence of other common adverse effects between the groups, including headache, dizziness, somnolence, or nasopharyngitis.
The researchers note that the trials included in the meta-analysis were all "high quality" and that "might minimize selection and measurement bias." However, the fact that they all used an intention-to-treat approach to avoid overestimating the efficacy effects could mean that the side effects are underestimated, they observed.
The IRLS and other efficacy measures used in the trials were subjective, and future trials could benefit from objective measurement of RLS. At the present time, the only means of doing this is by polysomnography.
Both long-term studies as well as more evidence of head-to-head comparisons of pramipexole with other dopamine agonists, anticonvulsants, and levodopa are needed, the researchers suggested.
The authors reported that they had no relevant conflicts of interest.