PURPOSE: A safety trial to determine the effect of sodium oxybate (SXB) on the apnea hypopnea index (AHI) in obstructive sleep apnea (OSA) was performed. SXB produced a statistically significant reduction in the AHI. This is a report of the effect of SXB on sleep architecture and excessive daytime sleepiness (EDS).
METHODS: Subjects (n=50) with a history of OSA and AHI between 10-40 events/h without serious hypoxia. The study had 2 phases: 1) randomized, single blind, placebo-controlled, crossover trial; with 4 consecutive nights with polysomnography (PSG), crossover design with randomization to either: placebo, SXB, SXB+modafinil (SXB+M), or zolpidem (ZOL; positive control); and 2), a double blind, placebo-controlled trial with 14-day treatment (SXB or placebo), then PSG with either SXB (9.0 g) or placebo. Sleep measures included total sleep time (TST), duration and proportion of stages 1-4, and REM sleep. EDS was assessed pre-and post-treatment using the Epworth Sleepiness Scale (ESS).
RESULTS: In phase 1, for SXB compared to placebo, these sleep parameters significantly increased: TST (median SXB = 434.3 min, placebo = 400.3), stage 3 (17.3 vs. 11.5), and stage 4 (71.0 vs. 25.5); and REM sleep (65.7 vs. 82.6) was reduced. SXB+M treatment did not alter TST, increased stage 3 and 4, and reduced REM. ZOL increased TST but didn't significantly alter any particular sleep stage. In phase 2, for SXB compared to placebo, TST was greater (430.5 vs. 405.5), stage 4 was significantly increased, and REM sleep was decreased (71.3 vs. 84.1). In the SXB and placebo groups, mean ESS decreased from pre- to post-treatment (-3.5 vs. -0.6 points).
CONCLUSION: In this study group, SXB associated with: increased TST and stage 3/4 sleep; reduced REM, and improved EDS.
CLINICAL IMPLICATIONS: Changes in sleep architecture may account for the reduction noted in the AHI with SXB. The ESS improvement suggests a possible role of SXB in the treatment of EDS associated with OSA.
DISCLOSURE: Neil Feldman, Grant monies (from industry related sources) yes.