Effects of tiagabine on slow wave sleep and arousal threshold in patients with obstructive sleep apnea

Luigi Taranto-Montemurro, Scott A. Sands, Bradley A. Edwards, Ali Azarbarzin, Melania Marques, Camila De Melo, Danny J Eckert, David P. White, Andrew Wellman

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

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] Log?V2, 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.

Original languageEnglish
Article numberzsw047
Number of pages7
JournalSleep
Volume40
Issue number2
DOIs
Publication statusPublished - 1 Feb 2017

Keywords

  • Arousal threshold
  • Sleep-disordered breathing
  • Slow-wave sleep
  • Tiagabine

Cite this

Taranto-Montemurro, Luigi ; Sands, Scott A. ; Edwards, Bradley A. ; Azarbarzin, Ali ; Marques, Melania ; De Melo, Camila ; Eckert, Danny J ; White, David P. ; Wellman, Andrew. / Effects of tiagabine on slow wave sleep and arousal threshold in patients with obstructive sleep apnea. In: Sleep. 2017 ; Vol. 40, No. 2.
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title = "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] Log?V2, 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.",
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author = "Luigi Taranto-Montemurro and Sands, {Scott A.} and Edwards, {Bradley A.} and Ali Azarbarzin and Melania Marques and {De Melo}, Camila and Eckert, {Danny J} and White, {David P.} and Andrew Wellman",
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Taranto-Montemurro, L, Sands, SA, Edwards, BA, Azarbarzin, A, Marques, M, De Melo, C, Eckert, DJ, White, DP & Wellman, A 2017, 'Effects of tiagabine on slow wave sleep and arousal threshold in patients with obstructive sleep apnea', Sleep, vol. 40, no. 2, zsw047. https://doi.org/10.1093/sleep/zsw047

Effects of tiagabine on slow wave sleep and arousal threshold in patients with obstructive sleep apnea. / Taranto-Montemurro, Luigi; Sands, Scott A.; Edwards, Bradley A.; Azarbarzin, Ali; Marques, Melania; De Melo, Camila; Eckert, Danny J; White, David P.; Wellman, Andrew.

In: Sleep, Vol. 40, No. 2, zsw047, 01.02.2017.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Effects of tiagabine on slow wave sleep and arousal threshold in patients with obstructive sleep apnea

AU - Taranto-Montemurro, Luigi

AU - Sands, Scott A.

AU - Edwards, Bradley A.

AU - Azarbarzin, Ali

AU - Marques, Melania

AU - De Melo, Camila

AU - Eckert, Danny J

AU - White, David P.

AU - Wellman, Andrew

PY - 2017/2/1

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N2 - 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] Log?V2, 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.

AB - 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] Log?V2, 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.

KW - Arousal threshold

KW - Sleep-disordered breathing

KW - Slow-wave sleep

KW - Tiagabine

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