Effect of sodium oxybate, modafinil, and their combination on disrupted nighttime sleep in narcolepsy.

OBJECTIVE: To assess the effects of three narcolepsy treatment modalities on sleep stage shifts associated with disrupted nighttime sleep (DNS) using data from a clinical trial. METHODS: Polysomnograms were reviewed from 155 patients (who had these data available at baseline and 8 weeks) of the 278 patients who were randomized to placebo, 9-g sodium oxybate (SXB)/nightly, 200-600 mg/d modafinil, or SXB + modafinil. Major outcomes of these post hoc analyses, analyzed using analysis of covariance, were change from baseline in number of shifts from Stages N2/3/rapid eye movement (REM) to Stage N1/Wake, and from Stage N1/Wake to REM. Sleep quality was evaluated using the sleep-quality question from the Pittsburgh Sleep Quality Index. RESULTS: SXB alone or in combination with modafinil significantly decreased the number of shifts from Stage N2/3/REM to Stage N1/Wake (p < 0.01); least-squares mean change in number of shifts from baseline was -0.6, -16.5, 1.8, and -13.7 in the placebo, SXB, modafinil and SXB + modafinil groups, respectively. A similar pattern was observed for changes in shifts from REM to Stage N1/Wake and from Stage N1/Wake to REM. Relative to placebo, sleep quality significantly improved with SXB and SXB + modafinil (p ≤ 0.05) but not with modafinil alone. CONCLUSION: These results show that SXB with and without modafinil significantly consolidated sleep and improved patient-reported sleep quality relative to placebo. In contrast, no such effects were observed with modafinil alone, suggesting a specific effect of SXB on DNS in addition to its effect on daytime sleepiness. CLINICALTRIALS. GOV IDENTIFIER: NCT00066170.

Effect of sodium oxybate on disrupted nighttime sleep in patients with narcolepsy.

This post hoc analysis evaluated the dose-related effects of sodium oxybate on sleep continuity and nocturnal sleep quality in patients with narcolepsy-cataplexy. Polysomnography data, including shifts to Stage N1/Wake, were from a randomized, placebo-controlled trial of sodium oxybate. Patients were ≥16 years old with a diagnosis of narcolepsy including symptoms of cataplexy and excessive daytime sleepiness. Treatment was for 8 weeks with placebo or sodium oxybate 4.5, 6 or 9 g administered as two equally divided nightly doses. Relative to baseline, significant dose-dependent reductions in the number of shifts per hour from Stages N2/3/rapid eye movement and Stages N2/3 to Stage N1/Wake were observed at week 8 with sodium oxybate (P < 0.05); sodium oxybate 6- and 9-g doses also resulted in similar reductions in shifts per hour of rapid eye movement to Stage N1/Wake (both P < 0.05). Across all shift categories, the shift reductions with sodium oxybate 9 g were significantly greater than those observed with placebo (P < 0.05). Improvements from baseline in reported sleep quality were significantly greater with sodium oxybate 4.5 and 9 g at week 8 (P < 0.05). Correlations between change from baseline in number of shifts per hour to Stage N1/Wake and cataplexy frequency, patient-reported nocturnal sleep quality, and excessive daytime sleepiness assessed using the Epworth Sleepiness Scale were numerically highest for the sodium oxybate 9-g dose across all sleep stage shift categories. In these patients with narcolepsy, sodium oxybate showed improvements in the sleep continuity and nocturnal sleep quality that are characteristic of disrupted nighttime sleep (ClinicalTrials.gov identifier NCT00049803).