Rotigotine improves restless legs syndrome: a 6-month randomized, double-blind, placebo-controlled trial in the United States.

This randomized, double-blinded, placebo-controlled trial (NCT00135993) assessed efficacy and safety of the dopamine agonist rotigotine in the treatment of idiopathic restless legs syndrome (RLS) over a 6-month maintenance period. A total of 505 eligible participants with moderate to severe RLS (IRLS sum score >or= 15) were randomly assigned to five groups to receive either placebo or rotigotine (0.5, 1, 2, or 3 mg/24 hr) delivered by once-daily transdermal patch (fixed-dose regimen). The two co-primary efficacy parameters decreased from baseline to end of maintenance in IRLS sum score and in clinical global impressions (CGI-1) score. On both primary measures, 2 and 3 mg/24 hr rotigotine was superior to placebo (P < 0.001). Adjusted treatment differences to placebo for the IRLS sum score were -4.5 (95% CI: -6.9, -2.2) for 2 mg/24 hr rotigotine, -5.2 (95% CI: -7.5, -2.9) for 3 mg/24 hr rotigotine, and for CGI item 1 -0.65 (95% CI: -1.0, -0.3) and -0.9 (95% CI: -1.3, -0.5) for the 2 and 3 mg/24 hr doses, respectively. Skin reactions (27%) and known dopaminergic side effects such as nausea (18.1%) and headache (11.6%) were mostly mild or moderate in rotigotine subjects. Rotigotine transdermal patches releasing 2 to 3 mg/24 hr significantly reduced the severity of RLS symptoms. Treatment efficacy was maintained throughout the 6-month double-blind period.

Ropinirole in the treatment of patients with restless legs syndrome: a US-based randomized, double-blind, placebo-controlled clinical trial.

OBJECTIVE: To assess the efficacy, safety, and tolerability of the dopamine agonist ropinirole in the treatment of patients with moderate to severe primary restless legs syndrome (RLS). PATIENTS AND METHODS: This multicenter, 12-week, double-blind, placebo-controlled, flexible-dose study enrolled US patients and was conducted between September 2003 and May 2004. Patients were randomized to ropinirole or placebo, 0.25-4.0 mg as needed and tolerated, once daily, 1 to 3 hours before bedtime. The primary end point was mean change from baseline to week 12 in International Restless Legs Scale (IRLS) total score. Key secondary efficacy measures included the Clinical Global Impression-Improvement scale. RESULTS: A total of 381 patients were enrolled; 164 (87.7%) of 187 patients randomized to ropinirole and 167 (86.1%) of 194 randomized to placebo completed the study. Significant treatment differences favoring ropinirole, compared with placebo, were observed for change in IRLS total score at week 12 (adjusted mean treatment difference, -3.7; 95% confidence interval, -5.4 to -2.0; P < .001) and for all 3 key secondary end points: mean change from baseline in IRLS total score at week 1 and proportion of patients who were much/very much improved on the Clinical Global Impression Improvement scale at weeks 1 and 12. Ropinirole was associated with significantly greater Improvements in subjective measures of sleep disturbance, quantity, and adequacy; quality of life; and anxiety. Although treatment differences favoring ropinirole in daytime somnolence were observed, they were not statistically significant (P = .10). Ropinirole was generally well tolerated, with an adverse-event profile consistent with other dopamine agonists. CONCLUSION: This study confirms that ropinirole improves RLS symptoms and subjective measures of sleep, quality of life, and anxiety and that it is generally well tolerated.

Sleep and residual sedation after administration of zaleplon, zolpidem, and placebo during experimental middle-of-the-night awakening.

STUDY OBJECTIVES: To assess the efficacy of zaleplon 10 mg and zolpidem 10 mg administered during experimental middle-of-the-night awakenings in patients with sleep-maintenance insomnia using objective polysomnographic measures and to assess daytime residual sedation 4 to 7 hours after dosing using sleep-latency testing. DESIGN: A randomized, double-blind, placebo-controlled, 3-period, crossover design was used to study 37 adults with insomnia who received treatment during an experimental awakening 4 hours after bedtime. Latency to persistent sleep and total sleep time before and after awakening were recorded. The primary residual sedation measure was a sleep latency test conducted hourly from 4 to 7 hours after treatment. Self-report measure of alertness and concentration and digit symbol substitution tests were examined concurrently. SETTING: Sleep disorders centers. PATIENTS: Thirty-seven adults with sleep-maintenance insomnia. INTERVENTIONS: Zaleplon 10 mg, zolpidem 10 mg, or placebo. MEASUREMENTS AND RESULTS: Thirty-one patients had efficacy-evaluable data; 37 patients received at least 1 dose of study medication and were included in the safety analysis. Compared with placebo, latency to persistent sleep after both zaleplon and zolpidem was shorter and total sleep time after administration of the drugs was longer (overall p < .001, Dunnett p < .001 for all posthoc comparisons). Significant differences from placebo were not found with zaleplon in daytime-sedation measures. At 4, 5, and 7 hours after zolpidem, sleep onset on sleep latency testing was shorter than after placebo (overall p < .001 for all, Dunnett tests for posthoc comparisons p < .001, p < .001, p < .05, respectively). Self-report measures of concentration (4, 5, and 6 hours, overall p < .05, Dunnett p < .05 for each time point) and alertness (4 hours, overall p < .05, Dunnett p < .05), and Digit Symbol Substitution Test scores (4 and 5 hours, overall p < .001, Dunnett p < .01 for both time points) after zolpidem were also lower than with placebo. CONCLUSIONS: Zaleplon 10 mg and zolpidem 10 mg effectively shorten sleep latency and lengthen sleep duration after dosing, when administered during experimental nocturnal awakening. Residual sedation was not detected as little as 4 hours after zaleplon 10 mg, whereas residual sedation was detected with zolpidem 10 mg up to 7 hours after treatment. These findings suggest that zaleplon may be an appropriate treatment for use when patients awaken during the night and have difficulty reinitiating sleep.

Ropinirole decreases periodic leg movements and improves sleep parameters in patients with restless legs syndrome.

STUDY OBJECTIVES: 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). DESIGN: Double-blinded, placebo-controlled, parallel-group study. SETTING: 15 tertiary referral centers in the USA. PARTICIPANTS: 65 patients with RLS and PLMS. INTERVENTIONS: Ropinirole (0.25-4.0 mg per day) or placebo for 12 weeks. MEASUREMENTS AND RESULTS: 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. CONCLUSIONS: Ropinirole is effective in the treatment of both the sleep and waking symptoms of RLS.

Efficacy and safety of modafinil for improving daytime wakefulness in patients treated previously with psychostimulants.

OBJECTIVES: To assess the efficacy and safety of modafinil for improving wakefulness in narcolepsy patients treated previously with psychostimulants. BACKGROUND: Modafinil has become a standard therapy for improving daytime wakefulness in narcolepsy patients and may be a useful therapeutic alternative to psychostimulants used to improve waking function in other medical conditions. Modafinil is chemically dissimilar to and has a pharmacological profile that differs from the psychostimulants. Modafinil has a low abuse potential and is well tolerated. METHODS: Patients (N=151) with narcolepsy who had been unsatisfactorily treated with dextroamphetamine (N=48), methylphenidate (N=66), or pemoline (N=37) were enrolled in this 6-week, open-label, multicenter study. Following a 2-week washout period, patients received modafinil once daily (Week 1, 200 mg; Weeks 2-6, 200 or 400 mg). Efficacy was evaluated at Weeks 1, 2, and 6 using the Epworth Sleepiness Scale and the Clinical Global Impression of Change. Adverse events were monitored throughout the study. RESULTS: Treatment with modafinil improved daytime wakefulness versus baseline regardless of which psychostimulant was taken previously. Mean ESS scores were improved after 1 week of treatment with modafinil. Improvements were maintained throughout the 6 weeks of treatment (all P<0.001 versus baseline after washout). At Week 6, 79% of all patients were considered to be clinically improved relative to post-washout baseline. The most frequent adverse events were headache, nausea, and insomnia; the majority of adverse events were mild or moderate in nature. Approximately 70% of patients were receiving 400 mg of modafinil once daily at the end of the study. CONCLUSION: During this 6-week, open-label study, modafinil was an effective and well-tolerated treatment for improving daytime wakefulness in narcolepsy patients previously treated with psychostimulants.

Posttraumatic stress disorder in the spouse of a patient with sleep terrors.

A 27-year-old woman who developed posttraumatic stress disorder (PTSD) as a consequence of her husband's severe sleep terror episode is reported. A 29-year-old man suddenly aroused from sleep and jumped through the closed second-story window of the room he shared with his wife, sustaining major lacerations to his arms. He hung onto the roof as his wife screamed at him from the window, and eventually climbed back inside. He was evaluated with polysomnography and was given the diagnosis of sleep terrors, which was effectively treated with behavioral and pharmacologic interventions. During a routine follow-up visit with the patient, his wife's PTSD symptoms came to clinical attention and she was referred for treatment. She demonstrated marked improvement in her condition after an 8 week course of cognitive-behavioral therapy. We conclude that family members of patients with sleep disorders manifesting as violent behaviors during sleep can suffer psychological trauma even if they are not physically injured.