Modafinil for the treatment of daytime sleepiness in Parkinson's disease: a double-blind, randomized, crossover, placebo-controlled polygraphic trial.

OBJECTIVES: To assess the therapeutic efficacy of modafinil in the treatment of increased daytime sleepiness in patients with Parkinson's disease (PD). DESIGN: Double-blind, randomized, placebo-controlled crossover study with two 2-week treatment blocks, separated by a 2-week washout phase. SETTING: Tertiary Parkinson's disease care center and sleep laboratory at university hospital neurology department. PATIENTS: Fifteen patients with idiopathic PD and daytime sleepiness (Epworth sleepiness score (ESS) 10 or more). INTERVENTIONS: Administration of placebo or modafinil as a single morning dose in a randomized crossover order. The modafinil dose was 100 mg in the first, and 200 mg in the second treatment week. MEASUREMENTS AND RESULTS: At baseline and at the end of each treatment block, sleepiness was evaluated using subjective (perceived sleepiness with the ESS) and objective measures (maintenance of wakefulness test). Twelve patients completed the study (9 male, 3 female; mean age 65.0 +/- 7.6 years, mean disease duration 6.8 +/- 4.1 years). Epworth scores were significantly improved with modafinil (3.42 +/- 3.90) compared to placebo (0.83 +/- 1.99; p = 0.011). Latency to sleep in the maintenance of wakefulness test was not significantly altered by modafinil treatment: 10.9 (3-40)/15.1 (2.5-40) minutes before/after placebo and 12 (2.6-40)/17.8 (4.2-40) minutes before/after modafinil (p = 0.139) [data given as mean +/- standard deviation or median (range)]. CONCLUSIONS: The results of this study suggest that modafinil improves daytime sleepiness in PD patients, at least on a subjective or behavioral level. Modafinil treatment may be considered for EDS in PD patients, in whom otherwise treatable causes of Excessive Daytime Sleepiness (EDS) are absent.

Irresistible onset of sleep during acute levodopa challenge in a patient with multiple system atrophy (MSA): placebo-controlled, polysomnographic case report.

A 67-year-old male patient with clinically probable multiple system atrophy developed severe reproducible sleepiness and irresistible onset of sleep during an acute levodopa (L-dopa) challenge. In a placebo-controlled, double-blind study of acute L-dopa challenge, videopolysomnography revealed multiple episodes of non-rapid eye movement sleep 60 minutes after L-dopa and none following placebo. These observations suggest the irresistible sleep can also be induced by L-dopa and also in patients with atypical parkinsonism.

Riluzole in Huntington's disease (HD): an open label study with one year follow up.

In an open label study, we administered riluzole (50 mg twice a day) to nine patients with genetically confirmed Huntington's disease (HD) (clinical stages 1-3; mean age 46.4 (SD 9.3) years; mean disease duration 8 (SD 3.3) years). The study was designed to evaluate (1) safety and tolerability of riluzole and (2) effects of riluzole on motor impairment, functional disability, cognitive impairment, and behavioral abnormalities using the Unified HD Rating Scale. Patients were evaluated at baseline and after three and twelve months of riluzole therapy. Laboratory tests (hematology and liver enzymes) were repeated monthly. All adverse experiences, reported spontaneously or observed directly by the investigator, were recorded. Riluzole was well tolerated. No increase of serum liver enzymes was seen throughout the study in all but one patient showing a mild elevation. At three months, mean total motor scale (TMS), mean TMS chorea subscore, and mean total functional capacity scale were significantly improved compared with baseline. At twelve months, however, this beneficial effect on motor status and overall function was not sustained. In contrast, severity and frequency of behavioral dysfunction as well as psychomotor speed assessed by the symbol digit modalities test were improved compared with baseline. Our data suggest that there are transient antichoreatic effects and more sustained effects of riluzole on psychomotor speed and behavior in patients with HD. A double-blind, placebo-controlled trial appears highly warranted to establish definitely the symptomatic versus neuroprotective actions of riluzole in HD.