Sodium oxybate for excessive daytime sleepiness in Parkinson disease: an open-label polysomnographic study.

BACKGROUND: Many patients with Parkinson disease (PD) have excessive daytime sleepiness and numerous nocturnal sleep abnormalities. OBJECTIVE: To determine the safety and efficacy of the controlled drug sodium oxybate in a multicenter, open-label, polysomnographic study in subjects with PD and sleep disorders. Design, Setting, and Patients Inclusion required an Epworth Sleepiness Scale (ESS) score greater than 10 and any subjective nocturnal sleep concern, usually insomnia. An acclimation and screening polysomnogram was performed to exclude subjects with sleep-disordered breathing. The following evening, subjects underwent another polysomnogram, followed by an evaluation with the Unified Parkinson Disease Rating Scale (UPDRS) while practically defined off ("off") PD medications, ESS (primary efficacy point), Pittsburgh Sleep Quality Inventory, and Fatigue Severity Scale. Subjects then started sodium oxybate therapy, which was titrated from 3 to 9 g per night in split doses (at bedtime and 4 hours later) across 6 weeks, and returned for subjective sleep assessments. They then returned at 12 weeks after initiating therapy for a third polysomnogram, an off-medication UPDRS evaluation, and subjective sleep assessments. Data are expressed as mean (SD). RESULTS: We enrolled 38 subjects. At screening, 8 had sleep apnea (n = 7) or depression (n = 1). Twenty-seven of 30 subjects completed the study. Three dropped out owing to dizziness (n = 3) and concurrent depression (n = 1). The mean dose of sodium oxybate was 7.8 (1.7) g per night. The ESS score improved from 15.6 (4.2) to 9.0 (5.0) (P < .001); the Pittsburgh Sleep Quality Inventory score, from 10.9 (4.0) to 6.6 (3.9) (P < .001); and the Fatigue Severity Scale score, from 42.9 (13.2) to 36.3 (14.3) (P < .001). Mean slow-wave sleep time increased from 41.3 (33.2) to 78.0 (61.2) minutes (P = .005). Changes in off-medication UPDRS scores were not significant, from 28.4 (10.3) to 26.2 (9.6). CONCLUSION: Nocturnally administered sodium oxybate improved excessive daytime sleepiness and fatigue in PD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00641186.

An open-label pilot study of levetiracetam for essential tremor.

The objective of this study was to determine whether levetiracetam warrants further investigation as a treatment of essential tremor (ET). The authors conducted a 4 -week, open label trial of levetiracetam (Keppra, UCB Pharmaceuticals) in 10 patients diagnosed with ET. Patients were assessed with the complete Tremor Rating Scale (TRS), global impression measures, and adverse events at baseline, after 2 weeks low-dose 500 mg bid and at 4 weeks high-dose 1500 mg bid. All 10 subjects (mean age, 68.6 +/- 7.4 years; seven men, 9 with a positive family history of ET) completed the trial. The TRS observed tremor section modestly improved in 8 subjects (P <0.01). The TRS writing section, water pouring section, and activities of daily living section did not change, and visual analog scores did not change. Subjects rated themselves as "much improved" (n=3), moderately improved (n=1), unchanged (n=1), and mildly worse (n=5). Adverse events included dizziness (n=2), sedation (n=1), and nervousness (n=1). Levetiracetam was well tolerated but failed to improve tremor consistently in this small trial.