乌鸦传媒

NEW ORLEANS -- Narcolepsy patients troubled by frequent nighttime awakenings had less sleep disruption when taking sodium oxybate (Xyrem) than modafinil (Provigil) in a randomized trial, a researcher reported here.

Measurements of disrupted nighttime sleep -- specifically, the number of shifts per night from sleep stages 2-4 or REM sleep to stage 1 or full wakefulness as determined from polysomnography -- showed no change from baseline in the group assigned to modafinil, whereas there was a median reduction of 13.0 shifts from a baseline mean of 40.9 in the patients taking sodium oxybate, according to , of Hospital Gui-de-Chauliac in Montpellier, France.

Patients taking placebo on the same schedule as sodium oxybate (a second dose taken in the night, 2.4-4.0 hours after the first dose at bedtime) showed a median reduction from baseline of 1.5 shifts/night (P<0.001 versus sodium oxybate), Dauvillier said at the American Neurological Association annual meeting.

A fourth arm in the 8-week, 222-patient trial received both sodium oxybate and modafinil. In that group, the change from baseline in sleep shifts from baseline was nearly the same as in the group receiving sodium oxybate alone (11.5 per night), as would be expected from the lack of effect seen with modafinil alone.

And, Dauvilliers reported, patients' self-assessments of sleep quality paralleled the polysomnography results, with little to no change in the placebo and modafinil monotherapy groups, and nearly equal improvements in the patients taking sodium oxybate alone and sodium oxybate combined with modafinil.

However, session co-moderator , of Vanderbilt University in Nashville, told 乌鸦传媒 that the study did not change her opinion of sodium oxybate as a treatment of last resort for patients with disordered sleep.

Noting the -- for example, patients have to awaken midway through the night to take a second dose, and the drug has serious abuse potential and toxicities -- Malow said she would still try patients first on other drugs, including modafinil and its cousin armodafinil (Nuvigil), before recommending sodium oxybate.

"I'm kind of conservative," she said. "I would also think about making sure that their sleep habits are where they need to be, making sure they're not using caffeine too late in the day, making sure they're getting enough exercise."

Narcolepsy is chiefly marked, of course, by involuntarily falling asleep during the day when individuals want to be awake. But many narcolepsy patients have the reverse problem at night, with frequent unwanted awakenings. As the baseline data in the current study showed, this may occur dozens of times during the night in a narcolepsy population.

Sodium oxybate is currently FDA-approved for treating cataplexy and excessive daytime sleepiness in narcolepsy. Its effectiveness for smoothing disordered nighttime sleep in narcolepsy patients had not previously been established.

The current study was a secondary analysis of a previously reported phase III trial comparing sodium oxybate, modafinil, a combination of both drugs, and placebo in a double-blind, double-dummy fashion, involving patients entering the study on stable doses of modafinil. As part of the trial, patients underwent polysomnography studies at baseline and after 8 weeks of treatment, allowing nighttime effects of the study drugs to be analyzed.

Patients were initially observed for 1-2 weeks on modafinil, followed by another 2-week phase in which they took modafinil at their previous dosage plus a placebo substitute for sodium oxybate given at bedtime and midway through the night. Patients then entered the double-blind, randomized phase. In the groups assigned to active sodium oxybate, the dosage was 6 g/night for the first 4 weeks and then 9 g/night for the last 4 weeks.

Dauvilliers noted that treatment-emergent adverse effects, both overall and leading to discontinuation, were more common in the groups receiving sodium oxybate. Four patients taking the drug plus modafinil placebo and six taking both active drugs dropped out of the study because of adverse effects, compared with three patients in the other two groups combined.

Nausea, vomiting, and dizziness were the adverse effects that were significantly (P≤0.01) more common with sodium oxybate than modafinil or placebo.

More serious adverse effects were rare in the study and not more common with sodium oxybate. However, the about risk of life-threatening central nervous system depression. For this reason and its abuse potential (it has been used as a "date rape" drug because of its rapid induction of sleep), sodium oxybate is available only through a restricted distribution system in which prescribers and patients must enroll.

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