NEW ORLEANS – Pregabalin proved better than pramipexole for relieving restless legs syndrome, and it caused less symptom augmentation, in a yearlong trial funded by Pfizer, the manufacturer of pregabalin.
Dopamine agonists such as pramipexole (Mirapex) are first-line agents for restless legs syndrome (RLS), but over time they can actually make symptoms worse.
That’s a problem because "we are going to use these treatments for most of the patient’s life," lead investigator Dr. Diego Garcia-Borreguero, director of the Sleep Disorders Institute in Madrid, said at the annual meeting of the American Academy of Neurology.
His team compared 300 mg/day of pregabalin (Lyrica), a calcium-channel modulator, in 182 RLS patients against 0.25 mg/day of pramipexole in 178 patients; 0.5 mg/day of pramipexole in 180; and placebo in 179.
After 12 weeks, placebo patients were randomized to an active treatment arm, and the trial continued for another 40 weeks. The mean age of patients was 55 years and their mean RLS duration was 5 years; more than half were women.
At 12 weeks, pregabalin patients were doing 3.96 points better on the 40-point international RLS rating scale (IRLS) than were patients on 0.25 mg/day of pramipexole, and 1.69 points better than were patients on 0.5 mg/day of pramipexole. At the end of the year, pregabalin patients were doing 3.8 points better on the IRLS than were the 0.25-mg/day pramipexole patients, and 3.06 points better than the 0.5-mg pramipexole patients.
Also at the end of the year, the rate of augmentation was 2.1% in the pregabalin group, 5.3% in the 0.25 mg pramipexole group (P value for difference with pregabalin = .083), and 7.7% in the 0.5 mg pramipexole group (P value for difference with pregabalin = .012).
Dizziness, somnolence, and weight gain were more common with pregabalin, whereas with pramipexole nausea and headache were more common.
"Pregabalin is more effective than pramipexole" for RLS, Dr. Garcia-Borreguero concluded. "It has less augmentation over the long term, and it has superior efficacy."
Even so, Pfizer has stated it currently does not plan to seek approval for the indication from the Food and Drug Administration or regulators in other countries.
In the United States, the drug is indicated for neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, adjunctive therapy for adult patients with partial onset seizures, and fibromyalgia.
On May 4, the company halted a trial for neuropathic pain associated with HIV neuropathy after pregabalin proved no better than placebo.
Dr. Garcia-Borreguero has received personal compensation for activities with Pfizer, UCB Pharma, XenoPort, and Otsuka.