Neurological Tidbits on Restless Legs
ABSTRACTS & COMMENTARIES
Palha and associates provide the results of a Double-Blind Controlled Trial of Gabapentin in Essential Tremor (ET) (Palha R, et al. Mov Disord 1998;13:465-467). Gabapentin in doses of 1800 mg/d was compared to placebo in a double-blind crossover study of 20 (minus 2 dropouts) patients with ET. Trial times lasted two weeks, during which 14 patients reported no change with placebo compared to 15 with no change taking gabapentin. One patient in each group claimed mild-to-moderate improvement, but there was no difference in scores on a Tremor Rating Score. Mild-to-moderate discomfort affected nine patients taking gabapentin, but only one patient on placebo complained of non-specific gastrointestinal symptoms.
In another study, Winkelmann and colleagues report Treatment of Restless Leg Syndrome (RLS) with Pergolide-An Open Clinical Trial (Winklemann J, et al. Mov Disord 1998;13566-569). Sinemet currently holds first choice in treating RLS, but the dopamine agonist, bromocriptine, has also been reported as beneficial (Walters, et al. Ann Neurol 1988;24:455-458). L-dopa, however, regrettably may sometimes precipitate an end-of-dose rebound and, sometimes, also brings on gradually worsening symptoms during the day as the illness lasts longer. Accordingly, some therapists have improved the condition by replacing L-dopa with the agonist, pergolide, taking advantage of its seven- to 16-hour operative half-life.
The authors treated 15 patients with RLS-13 of spontaneous origin and two with uremia. All had undergone an increase in adverse or RL symptoms while taking L-dopa. Specifically, day and nighttime RL symptoms had increased, RL intensity had increased, free-of-symptom time had shortened, and the phenomenon of RL had spread to the arms. For the pergolide trial, daily L-dopa was stopped no later than three days before starting pergolide. Pergolide dosage began at 0.05 mg before retiring and was accompanied by amperidone for two weeks to blunt side effects. Patients randomly and according to remaining symptoms increased pergolide dosage by 0.05 mg until movements readily improved. Progress was evaluated at six months.
All patients reported "dramatic" improvement in RL to a degree termed "no RLS" by the investigators. Side effects included: retention of sleep difficulties (3); stuffy noses (4); needing amperidone to quench nausea (1); and having vivid weekly dreams (1).
COMMENTARY
It is difficult to predict long-term outcome at this point since duration of successful treatment of RLS has lasted less than six months. Fortunately, no serious side effects have appeared. The largest question is: can the pergolide regimen keep the remarkable degree of amelioration of the RL syndrome for an importantly long time? Neurology Alert eagerly awaits further reports on longer evaluation times of this and other long-term series.
A similar study comes from Lin and associates, who addressed the Effect of Pramipexole in Treatment of Resistant RLS (Lin SC, et al. Mayo Clin Proc 1998;73:497-500). The authors previously conducted a successful pergolide trial (Drugs 1990;39:491-506) for patients resistant to levadopa. By 1997, however, benefits had declined. This open-label trial examines pramipexole, a nonergotdopamine receptor agonist recently reported by the Parkinson Study Group (JAMA 1997;278:125-130). The agent has a half-life of 8-12 hours and is well absorbed orally. Receiving patients were 62.4 ± 14.2 years; all had failed treatments of benzodiazepines, opioids, or opiates. Pretest treatment consisted of maintenance L-dopa (5) or pergolide (11), but patients had re-emergent RLS. Prior to study, all previous medication was halted. Pramipexole 0.125 mg was started two hours before retiring. Chronic dosages were reached within a few weeks. Fifteen of the 16 treated patients tolerated the drug. One withdrew because of insomnia. Mean ultimate daily dose of pramipexole was 0.3 ± 0.1. Using an arbitrary ranking from -4 (worst) to +4 (best), two patients developed involuntary leg movements (-4), whereas six improved 4+, five improved modestly, and four had almost no improvement. One-third of the patients complained of fatigue and stiffness; two-thirds reported amnesia. Evaluation was continued only to three months.
COMMENTARY
As was true for pergolide above, pramipexole produced modest improvement after all other efforts failed. Only time will tell, but both of these studies imply that available drugs successful for restless legs may often lose their effectiveness over long-term administration. -FP
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