Narcolepsy treatments similarly reduce daytime sleepiness in study
Trial findings were consistent across once- and twice-nightly formulations
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An analysis of five clinical studies found that different oxybate formulations similarly reduced daytime sleepiness in people with narcolepsy. (Image by iStock)
Different sodium oxybate formulations similarly reduced daytime sleepiness in adults with narcolepsy, despite differences in dosing schedules and sodium content, according to an analysis of five clinical trials.
The analysis found that these treatments reduced daytime sleepiness more than a placebo in studies involving more than 1,000 patients and generally had acceptable safety profiles during the studies.
“Larger trials with longer durations are warranted for validation,” the researchers wrote in the study, “Sodium oxybate for excessive daytime sleepiness in narcolepsy: a systematic review and meta-analysis of randomized placebo-controlled trials,” published in the DARU Journal of Pharmaceutical Sciences.
Sodium oxybate is a central nervous system depressant approved to treat excessive daytime sleepiness and cataplexy in narcolepsy.
Different formulations offer dosing options for narcolepsy
In the U.S., three oxybate-based medications are approved to treat daytime sleepiness or cataplexy in people with narcolepsy ages 7 and older. Xyrem is the original high-sodium oral solution, while Xywav is a newer low-sodium oral solution containing a mixture of oxybate salts. Both are taken twice nightly. Lumryz is an extended-release suspension taken once nightly.
Previous randomized controlled trials have shown that oxybate-based medications can reduce daytime sleepiness and cataplexy episodes (sudden losses of muscle tone) compared with placebo.
Researchers in India combined results from five trials to assess how consistently the treatments worked, their safety, and whether their effects differed by formulation.
According to the researchers, the five trials included 1,066 adults with narcolepsy (type 1 or 2). Participants had scores above 10 on the Epworth Sleepiness Scale, indicating excessive daytime sleepiness. Participants received one of the three formulations or a placebo during trials lasting eight to 13 weeks. The oxybate doses ranged from 4.5 to 9 g per night.
When researchers combined results from all five trials, Epworth Sleepiness Scale scores were an average of 4.8 points lower with sodium oxybate than with placebo, a statistically significant difference. Results varied moderately across studies.
The researchers noted that the pooled reduction “exceeds the minimal clinically important difference of 2-3 points established in sleep disorders, indicating clinically meaningful benefit.”
Results were similar when researchers analyzed each formulation separately. Compared with placebo, Epworth Sleepiness Scale scores were an average of 4.7 points lower with Xyrem, 4.7 points lower with Xywav, and 4.9 points lower with Lumryz.
Higher doses show no significant difference in sleepiness benefits
Compared with placebo, Epworth Sleepiness Scale scores were an average of 4.5 points lower at doses of 4.5 to 6 g per night and 5.2 points lower at doses of 7.5 to 9 g per night. Although the researchers noted a “trend toward a greater effect at higher doses,” the difference between the two dose groups was not statistically significant, meaning it could have been due to chance.
The researchers summarized other outcomes separately because the studies used different measurement scales and reported results differently. The researchers reported that one study of standard twice-nightly sodium oxybate found an increase of about 10 minutes in sleep latency at a 9 g nightly dose. The increase was measured using the Maintenance of Wakefulness Test, which assesses how long a person can stay awake during daytime testing. In another study, sleep latency increased by 3.5 minutes with Lumryz.
Nighttime sleep also improved. One study reported a median increase of 52.5 minutes in deep sleep (stages 3 and 4) at the 9 g dose. Another found that sleep efficiency, or the percentage of time in bed spent asleep, improved by 8.4%. Time spent awake after initially falling asleep decreased by 35.2 minutes. Cataplexy attacks also became less frequent in all four studies that reported this outcome.
The researchers reported nausea, dizziness, and headache among the most common adverse events, which were typically mild to moderate. Between 3% and 11% of oxybate-treated participants stopped treatment because of adverse events, including 4% with once-nightly Lumryz and 3% with low-sodium Xywav. Nausea and dizziness were more common at higher doses of 7.5 to 9 g per night.
The researchers concluded that sodium oxybate “significantly reduces excessive daytime sleepiness in narcolepsy,” with Epworth Sleepiness Scale scores averaging 4.8 points lower than with placebo. They emphasized the need for further research, noting that “larger trials with longer durations are warranted for validation.”
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