The nightly use of sodium oxybate is associated with a reduction in nocturnal sleep disruption: a double-blind, placebo-controlled study in patients with narcolepsy

Abstract

Objective: To further explore the effects of sodium oxybate (SXB) administration on nocturnal sleep in narcolepsy patients during a double-blind, placebo-controlled, parallel group study conducted with 228 adult patients with narcolepsy/cataplexy in the United States, Canada, and Europe.

Method: Patients were withdrawn from antidepressants and sedative/hypnotics, and then randomized to receive 4.5, 6, or 9 g SXB or placebo nightly for 8 weeks. Patients receiving 6 and 9 g/night doses were titrated to their final dose in weekly 1.5 g increments, while patients receiving placebo were randomized to undergo a similar mock dose titration. The use of stimulant therapy continued unchanged. Changes in sleep architecture were measured using centrally scored nocturnal polysomnograms. Daily diaries were used to record changes in narcolepsy symptoms and adverse events.

Results: Following 8 weeks of SXB treatment, study patients demonstrated significant dose-related increases in the duration of stage 3 and 4 sleep, reaching a median increase of 52.5 minutes in patients receiving 9 g nightly. Compared to placebo-treated patients, delta power was significantly increased in all dose groups. Stage 1 sleep and the frequency of nocturnal awakenings were each significantly decreased at the 6 and 9 g/night doses. The changes in nocturnal sleep coincided with significant decreases in the severity and frequency of narcolepsy symptoms.

Conclusions: The nightly administration of SXB to narcolepsy patients significantly impacts measures of slow wave sleep, wake after sleep onset, awakenings, total sleep time, and stage 1 sleep in a dose-related manner. The frequency and severity of narcolepsy symptoms decreased with treatment.

Keywords: Narcolepsy; delta power; polysomnography; sleep architecture; sodium oxybate.

Figures

Figure 1

Baseline cataplexy frequency was recorded during the 2-week lead-in phase. Antidepressant medications used for the treatment of cataplexy were withdrawn over a 21-day period following Visit 2 with the exception of fluoxetine, which was withdrawn beginning at Visit 1. The washout period lasted 5 days or 5 times the half-life of the withdrawn medication, whichever was longer, but did not exceed 18 days. Following randomization, patients were started on placebo in single-blind fashion and recorded baseline cataplexy occurrences over a 14-day period; however, this was extended to 21 days if the investigator felt cataplexy had not yet stabilized. Patients then received study medication or placebo and were titrated to their final dose, as shown. Polysomnography, the maintenance of wakefulness test, and assessment of narcolepsy symptoms were performed at Visits 2, 5, 6, and 7.