Treatment of Idiopathic Restless Legs Syndrome (RLS) with the D2-agonist Cabergoline — An Open Clinical Trial

Abstract

A DESIRE TO MOVE THE LEGS usually associated with paresthesias/dysesthesias, 2 motor restlessness, 3 worsening or exclusive presence of symptoms at rest (i.e., lying, sitting) with at least partial or temporary relief by activity, and 4 worsening of symptoms during the evening or night. According to the International RLS Study Group these four minimal criteria already allow clinical diagnosis. 1 Sensory and motor symptoms in RLS often result in severe sleep disturbances with prolonged sleep latency, decreased total sleep time with reduced or absent slow wave sleep and decreased sleep efficiency. Almost all RLS patients present periodic leg movements (PLM) during sleep and also while being awake. 2 In RLS patients the number of PLM and related parameters are often used as a marker for the severity of RLS since PLM are frequently associated with nocturnal arousals or awakenings. If present during wakefulness PLM may prevent patients from falling asleep. Therefore, performing polysomnography is mandatory to evaluate the efficacy of drug therapies. Various agents have been used to treat RLS. However, no substance is approved for this indication so far. The drug of first choice is levodopa in conjunction with a dopa decarStudy objectives: To define the effective dose of cabergoline and to evaluate the tolerability and efficacy of cabergoline in patients with restless legs syndrome (RLS). Design: Treatment of idiopathic RLS patients with cabergoline in a 12-week open label trial. Patients on levodopa therapy were allowed to either stop levodopa prior to study entry or to continue, taper or discontinue levodopa during the study. Efficacy parameters were assessed by polysomnography and subjective ratings at baseline and at week 12. Primary efficacy parameters were the number of PLM and total sleep time. Setting: Dept. of Neurology, Sleep Disorders Center Patients: Nine patients with moderate to severe RLS (age 38.1 to 64.3 years, mean 54.1 years) who had experienced insufficient benefit under levodopa therapy and/or in part developed daytime augmentation participated. At study entry five patients were still under levodopa therapy (400-800 mg). Interventions: Up-titration of cabergoline (single evening dose) until RLS symptoms clearly improved. Initial comedication with domperidone 20 mg t.i.d. Measurements and Results:At the endpoint all patients were on cabergoline monotherapy (mean dosage 2.1 mg, range 1 to 4 mg). Domperidone was stopped in all patients due to good tolerability. Polysomnographic data showed a significant reduction of the number of periodic leg movements (PLM) (195.8±109.1 (baseline) vs. 26.4±40.2 (12 weeks cabergoline monotherapy; p = 0.002), PLM arousals (51.7±42.3 vs. 6.4±11.2; p=0.017) and PLM awakenings (10.4±7.8 vs. 1.0±1.7; p=0.001). Total sleep time was prolonged (302.7±50.7 vs. 379.4±59.8 min; p=0.018), sleep latency shortened (42.4±49.1 vs. 16.3±22.8 min; p=0.214) and sleep efficiency increased (63.1±10.5 vs. 79.1±12.5%; p = 0.017). All patients reported a impressive relief or became free of ...

The Effect of Cabergoline on Sleep, Periodic Leg Movements in Sleep, and Early Morning Motor Function in Patients with Parkinson's Disease

“…The significant reduction of PLM under cabergoline treatment is in line with recent findings for cabergoline and other dopamine agonists in patients with PLM due to restless legs syndrome (Wetter et al, 1999;Montplaisir et al, 1999;Stiasny et al, 2000). As the frequency of arousals was not reduced during cabergoline therapy, this might indicate that PLMS are not the major cause for sleep fragmentation in PD patients.…”

Low-Dose Pramipexole in the Management of Restless Legs Syndrome

“…In parallel, levodopa was gradually reduced and discontinued -if possible -in patients who entered the study already taking levodopa. Therapeutic success was assessed by comparing sleep parameters of a one-night polysomnography at baseline (without an adaptation night) and at the end of up-titration using standard criteria (for details see [7]) as well as subjective ratings. The severity of RLS was rated by the patients using the 10-item International RLS Study Group Severity Scale (IRLS; 31-40 points: 'very severe'; 21-30: 'severe'; 11-20: 'moderate'; 1-10: 'mild' RLS) [13].…”

“…Consequently, these patients are frequently treated with multiple and higher daily doses of levodopa to control RLS symptoms. Another possibility is to substitute levodopa by a dopamine agonist, this has been shown to be successful in the case of pergolide [6] and cabergoline [7]. The therapeutic properties of the non-ergot dopamine agonist pramipexole, which has a high affinity to the D 3 receptor subtype of the D 2 family, have increasingly gained attention [8][9][10][11][12].…”

Restless Legs Syndrom bei Monozygoten und Dizygoten Zwillingen

“…Beteiligung des dopaminergen Neurotransmittersystems hin (Montplaisir et al 1986;Trenkwalder et al 1995;Stiasny et al 2000). Meist fanden sich in Untersuchungen des nigrostriatalen dopaminergen Systems mittels funktioneller bildgebender…”