Effects of Tiagabine on Slow Wave Sleep and Arousal Threshold in Patients With Obstructive Sleep Apnea

Abstract

Introduction: Obstructive sleep apnea (OSA) severity is markedly reduced during slow-wave sleep (SWS) even in patients with a severe disease. The reason for this improvement is uncertain but likely relates to non-anatomical factors (i.e. reduced arousability, chemosensitivity, and increased dilator muscle activity). The anticonvulsant tiagabine produces a dose-dependent increase in SWS in subjects without OSA. This study aimed to test the hypothesis that tiagabine would reduce OSA severity by raising the overall arousal threshold during sleep.

Aims and methods: After a baseline physiology night to assess patients' OSA phenotypic traits, a placebo-controlled, double-blind, crossover trial of tiagabine 12 mg administered before sleep was performed in 14 OSA patients. Under each condition, we assessed the effects on sleep and OSA severity using standard clinical polysomnography.

Results: Tiagabine increased slow-wave activity (SWA) of the electroencephalogram (1-4 Hz) compared to placebo (1.8 [0.4] vs. 2.0 [0.5] LogμV2, p = .04) but did not reduce OSA severity (apnea-hypopnea index [AHI] 41.5 [20.3] vs. 39.1 [16.5], p > .5). SWS duration (25 [20] vs. 26 [43] mins, p > .5) and arousal threshold (-26.5 [5.0] vs. -27.6 [5.1] cmH2O, p = .26) were also unchanged between nights.

Conclusions: Tiagabine modified sleep microstructure (increase in SWA) but did not change the duration of SWS, OSA severity, or arousal threshold in this group of OSA patients. Based on these findings, tiagabine should not be considered as a therapeutic option for OSA treatment.

Trial registration: ClinicalTrials.gov NCT02387710.

Keywords: arousal threshold; sleep-disordered breathing; slow-wave sleep; tiagabine.

© Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Figures

Figure 1

Group data of EEG power spectral density for the frequencies 1–32 Hz during all sleep stages (excluding arousals). Tiagabine did not have a specific effect on slow-wave activity but increased both delta (1–4 Hz) and theta (4–7 Hz) power.

Figure 2

Individual data showing changes in AHI (A) and arousal threshold (B) from placebo (P) to tiagabine (T) nights.