Polysomnographic study evaluating the efficacy of ropinirole for the treatment of patients with restless legs syndrome (RLS) suffering from periodic leg movements in sleep (PLMS).
Double-blinded, placebo-controlled, parallel-group study.
15 tertiary referral centers in the USA. Participants: 65 patients with RLS and PLMS.
Ropinirole (0.25-4.0 mg per day) or placebo for 12 weeks.
Data from 59 patients were included in the primary endpoint analysis. PLMS per hour decreased more with ropinirole (48.5 to 11.8), compared with placebo (35.7 to 34.2; adjusted treatment difference: -27.2; 95% confidence interval [CI]: -39.1, -15.4; P < .0001). Periodic limb movements with arousal per hour decreased from 7.0 to 2.5 with ropinirole but increased from 4.2 to 6.0 with placebo (adjusted treatment difference: -4.3, 95% CI: -7.6, -1.1; P = .0096). Periodic limb movements while awake per hour decreased from 56.5 to 23.6 with ropinirole but increased from 46.6 to 56.1 with placebo (adjusted treatment difference: -39.5; 95% CI: -56.9, -22.1; P < .0001). Ropinirole treatment significantly improved patients' ability to initiate sleep (P < .05) and the amount of Stage 2 sleep compared with placebo (P < .001). There were also non-significant trends toward increases in total sleep time and sleep efficiency. Sleep adequacy (measured on the subjective Medical Outcomes Study sleep scale) was significantly improved with ropinirole treatment (adjusted treatment difference: 12.1; 95% CI: 1.1, 23.1; P = .0316). In contrast, the placebo group showed a greater increase in Stage 3/4 sleep (P < .01). No serious adverse events occurred in either group.
Ropinirole is effective in the treatment of both the sleep and waking symptoms of RLS.
"Ropinirole exhibits a high affinity for D2 and D3 receptors, and controls nigrostriatal and mesolimbic-mesocortical dopaminergic activity.17 Clinical trials have shown that ropinirole significantly improves symptoms of RLS,18,19 producing scores on the mean International Restless Legs Scale (IRLS) that are 29-37% lower than those in placebo groups, and reducing periodic limb movements during sleep relative to baseline or placebo.20 Furthermore, ropinirole significantly improved the QoL in RLS patients compared to placebos. "
[Show abstract][Hide abstract] ABSTRACT: Dopamine agonists are first-line drugs for treating the symptoms of restless legs syndrome (RLS). However, few studies have investigated the effect of dopamine agonists on the quality of life (QoL) in RLS patients. We conducted a study to determine whether ropinirole exerts positive effects on the QoL in RLS patients and to analyze the underlying factors.
Primary RLS patients from eight medical centers were recruited in the study. They were evaluated in the baseline phase using various questionnaires including the Korean versions of the International Restless Legs Scale (K-IRLS), RLS QoL questionnaire (K-RLSQoL), and the Short Form 36 Health Survey (SF-36). After taking ropinirole for 8 weeks the same questionnaires were again completed as a re-evaluation. We analyzed the statistical difference using a paired t-test, a Pearson's correlation, and a stepwise multiple regression in order to identify the factors associated with the QoL change.
A total of 107 subjects, including 65 (60.7%) females, completed this study. They were aged 51.68±14.80 years (mean±SD) and had a symptom duration of 8.8±9.0 months. After treatment with ropinirole, there were significant improvements on the K-RLSQoL, SF-36, and K-IRLS. The Pearson's correlation analysis showed that the improvement of QoL in RLS patients was significantly correlated with the severity of RLS (r=0.236, p<0.014) at baseline.
The results from this study suggest that treatment with ropinirole can improve the QoL in RLS patients. The improvement in the QoL is more related with the improvement of RLS symptoms.
"Ropinirole and pramipexole demonstrated similar improvements in the change in IRLS total score from baseline of −12.0 and −16.9 after 52 weeks and 26 weeks, respectively.31,62 The dopamine agonists have also demonstrated improvements in sleep parameters according to polysomnography such as periodic limb movements of sleep, although improvements in sleep efficiency and sleep latency are inconsistent.33,63,64 "
[Show abstract][Hide abstract] ABSTRACT: The FDA approved gabapentin enacarbil in 2011 as the first non-dopaminergic agent for the treatment of restless legs syndrome (RLS) symptoms. Although gabapentin enacarbil is a pro-drug of gabapentin, its pharmacokinetics differ. Absorption of gabapentin enacarbil is more predictable, and inter-patient variability in bioavailability is lower than that of gabapentin. Studies have demonstrated superiority of gabapentin enacarbil compared to placebo. Comparisons to currently available RLS treatments are lacking, but clinical trials demonstrate comparable improvement in RLS symptoms to the dopamine agonists ropinirole and pramipexole, which are usually considered first-line therapy for daily RLS symptoms. Gabapentin enacarbil was well tolerated in clinical trials. The role of the drug in RLS treatment remains undefined, although it will likely be used as an alternative for refractory RLS when other treatments have failed. Additionally, gabapentin enacarbil may be recommended for patients with daily RLS symptoms that are less intense or are associated with pain as an alternative to dopamine agonists.
"However, patients within groups were heterogeneous in terms of medication and comorbidities, thus representing a typical patient cohort in a sleep clinic. This heterogeneity contrasts with other studies that investigated patients with RLS and/or PLM excluding patients with medication influencing motor activity during sleep or significant sleep disorder or major comorbidities (Allen et al., 2004; Garcia-Borreguero et al., 2004; Hornyak et al., 2004; Ferri et al., 2006a,b, 2009; Manconi et al., 2007). "
[Show abstract][Hide abstract] ABSTRACT: Periodic leg movements (PLM) during sleep consist of involuntary periodic movements of the lower extremities. The debated functional relevance of PLM during sleep is based on correlation of clinical parameters with the PLM index (PLMI). However, periodicity in movements may not be reflected best by the PLMI. Here, an approach novel to the field of sleep research is used to reveal intrinsic periodicity in inter movement intervals (IMI) in patients with PLM.
Three patient groups of 10 patients showing PLM with OSA (group 1), PLM without OSA or RLS (group 2) and PLM with RLS (group 3) are considered. Applying the "unfolding" procedure, a method developed in statistical physics, enhances or even reveals intrinsic periodicity of PLM. The degree of periodicity of PLM is assessed by fitting one-parameter distributions to the unfolded IMI distributions. Finally, it is investigated whether the shape of the IMI distributions allows to separate patients into different groups.
Despite applying the unfolding procedure, periodicity is neither homogeneous within nor considerably different between the three clinically defined groups. Data-driven clustering reveals more homogeneous and better separated clusters. However, they consist of patients with heterogeneous demographic data and comorbidities, including RLS and OSA.
The unfolding procedure may be necessary to enhance or reveal periodicity. Thus this method is proposed as a pre-processing step before analyzing PLM statistically. Data-driven clustering yields much more reasonable results when applied to the unfolded IMI distributions than to the original data. Despite this effort no correlation between the degree of periodicity and demographic data or comorbidities is found. However, there are indications that the nature of the periodicity might be determined by long-range interactions between LM of patients with PLM and OSA.
Frontiers in Neuroscience 09/2010; 4. DOI:10.3389/fnins.2010.00058 · 3.66 Impact Factor
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