Objective: To investigate the efficacy and safety of levodopa plus benserazide in the treatment of restless legs syndrome (RLS), in terms of the frequency of periodic limb movements (PLMs), objective and subjective criteria of sleep, onset of action, and withdrawal effects.
Design: A randomized, double-blind, placebo-controlled, multicenter, crossover trial, with two 4-week treatment periods.
Setting: Outpatient units of three specialist centers in Germany.
Patients: Eligible patients had to fulfill the diagnostic criteria of the International RLS Study Group and have sleep disturbances and PLMs during sleep shown on polysomnography at screening. Thirty-five patients were recruited, of whom 32 (13 men, 19 women) completed the study.
Interventions: Patients received a single dose of standard-release levodopa/benserazide 100/25 mg or placebo at bedtime each night for 4 weeks, before crossing over to receive the alternative treatment for a further 4 weeks; the dose could be doubled if required. The average dosages were 159 +/- 31 mg of levodopa and 1.56 +/- 0.29 capsules of placebo.
Results: Levodopa/benserazide significantly reduced the number of PLMs per hour (p<0.0001), increased the time in bed without limb movements (p<0.0001), and improved subjective quality of sleep (p=0.0004). The onset of action was rapid after the first dose, and full efficacy was achieved within the first few days of therapy; these improvements disappeared immediately when treatment was discontinued. Levodopa/benserazide treatment was well tolerated and safe.
Conclusions: Levodopa/benserazide is effective and safe in the treatment of RLS. Objective and subjective measures of sleep improved rapidly after the first dose. RLS symptoms recurred immediately after treatment was discontinued.