MIAMI BEACH – Sodium oxybate significantly lessened daytime sleepiness and decreased frequency of sleep attacks in people with narcolepsy concurrently taking stimulants, compared with placebo, according to study findings presented at the annual meeting of the American Academy of Neurology.
Previous studies have shown that nightly administration of sodium oxybate (Xyrem, Orphan Medical) effectively treated cataplexy in people with narcolepsy (Sleep 2003;26:31–5; Sleep 2002;25:42–9).
The Food and Drug Administration approved the agent for treatment of cataplexy, a sudden loss of muscle tone associated with narcolepsy, in July 2002. Researchers in the two studies observed that the drug also decreased excessive daytime sleepiness.
To confirm this effect, Dr. Michael J. Thorpy conducted an 8-week, double-blind, placebo-controlled trial of adult narcolepsy patients from 42 sleep clinics in the United States, Canada, and Europe. Participants, after being weaned from anticataplectic medications, were randomized to receive 4.5 g, 6 g, or 9 g of sodium oxybate or placebo nightly.
The drug was administered in two equally divided doses at bedtime and 2.5–4 hours later. Sodium oxybate was increased weekly in 1.5-g increments up to the final dose, with the total treatment lasting 28 days.
There were 228 patients in the intent-to-treat population, half randomized to treatment and half to placebo. A total of 206 completed the 8-week study. The majority (78%) remained on steady doses of preexisting stimulant medications.
“I don't think we know the mechanism of action. We understand GABA-B [gamma-aminobutyric acid B] mechanism regarding nighttime sleep. Sodium oxybate affects a number of neurotransmitter systems, and tends to depress dopamine at night,” Dr. Thorpy, director of the Sleep-Wake Disorders Center at the Montefiore Medical Center, New York, said in response to a question from the audience. Dr. Thorpy received support from Orphan Medical Inc., sponsor of the study.
Dr. Thorpy used the Maintenance of Wakefulness Test (MWT) as an objective measure of excessive daytime sleepiness, and the Epworth Sleepiness Scale (ESS) for a subjective assessment. Participants also kept diaries to record the incidence of sleep attacks. Changes in MWT scores at 8 weeks were significant, compared with baseline for patients receiving the final doses of either 4.5 g or 9 g. “Compared with placebo, patients treated with sodium oxybate showed a significant median increase in more than 10 minutes in MWT at the 9-g dose,” Dr. Thorpy said.
Baseline ESS scores were “around 19, suggesting a lot of sleepiness,” Dr. Thorpy said. The 6-g and 9-g treatment groups experienced statistically significant decreases in median ESS scores after 8 weeks, compared with baseline.
The weekly incidence of inadvertent naps was 14 to 18 overall at baseline. There were statistically significant reductions in these sleep attacks in the 6-g and 9-g groups, a mean of 6.5 fewer naps with treatment, compared with placebo.