Acute Dopamine-Agonist Treatment in Restless Legs Syndrome: Effects on Sleep Architecture and NREM Sleep Instability

RESTLESS LEGS SYNDROME (RLS) IS OFTEN ASSOCIATED WITH INSOMNIA, IN TERMS OF DIFFICULTY IN FALLING ASLEEP, SLEEP MAINTENANCE, AND SLEEP duration.1 Thus, sleep disruption mainly comes from the subjective report of patients and from the clinical experience of physicians. The severity of RLS-related insomnia ranges widely, from patients who seek treatment only for insomnia and underestimate their sensory symptoms to those who have no sleep complaints at all because the sensory symptoms are mild, rare, or occur prior to bedtime. Thus, insomnia is not considered necessary for or supportive of the diagnosis of RLS.1 Only a few studies have focused on the objective polysomnographic features of RLS; they have found an increase in sleep latency and a decrease in sleep efficiency only in patients with the most severe RLS symptoms.2–6 Except for the generic amount of arousals, no extensive data are available on sleep microstructure in RLS, as compared with age-matched normal control subjects. A very recent study demonstrated that sleep microstructure analysis by means of the cyclic alternating pattern (CAP)7 is helpful in understanding the mechanisms of subjective sleep perception (and misperception) in insomniacs.8 In addition, emerging evidence is available on a possible role for CAP in sleep-related cognitive processing, and sleep loss is thought to be an important factor affecting cognitive performance of patients with RLS. Periodic leg movements during sleep (PLMS) represent a very frequent objective finding in RLS, the contribution of PLMS to sleep disruption and sleep quality is an ongoing discussion.9,10 Dopamine-receptor agonists are remarkably effective and well-tolerated agents for the treatment of RLS; low evening doses of the D3-agonists pramipexole and ropinirole have become the first-line treatment for RLS.11,12 Controlled studies that include polysomnography recordings have provided evidence that ropinirole and pramipexole are effective in reducing both subjective symptoms of RLS and PLMS, even after a first single administration, in patients with RLS. On the contrary, the effects on sleep architecture have been reported in only a few studies, which failed to find extensive modifications of objective polysomnography-derived measures, other than PLMS.2–6 Even with successful treatment of the sensory symptoms of RLS, sleep problems may persist.13,14 Response to dopaminergic medications, together with positive family history and presence of PLMS, is considered to be an important supportive criterion for the diagnosis of RLS.1 The placebo effect in RLS treatment is a major issue that can impair the clinical judgment. The primary outcome measure in most studies, the International Restless Legs Syndrome Rating Scale, has been shown to yield a large placebo effect.15 In brief, the placebo effect seems to be large for subjective parameters but much smaller for objective parameters derived from polysomnography. To our knowledge, there are no studies on CAP in RLS and on the therapeutic effect of dopamine agonists on CAP in these patients. For all of these reasons, the aim of the present investigation was to analyze, in detail, the eventual baseline differences in CAP between normal control subjects and patients with RLS and the eventual changes in sleep architecture and instability induced by the acute administration of pramipexole in patients with RLS.