Single-use suvorexant for treating insomnia during overnight polysomnography in patients with suspected obstructive sleep apnea: a single-center experience

Drug Design, Development and Therapy Dovepress open access to scientific and medical research Original Research Drug Design, Development and Therapy downloaded from https://www.dovepress.com/ by 88.198.20.149 on 18-Oct-2019 For personal use only. Open Access Full Text Article Single-use suvorexant for treating insomnia during overnight polysomnography in patients with suspected obstructive sleep apnea: a single-center experience This article was published in the following Dove Medical Press journal: Drug Design, Development and Therapy Takuma Matsumura 1 Jiro Terada 1 Chikara Yoshimura 2 Ken Koshikawa 1 Taku Kinoshita 1 Misuzu Yahaba 1 Kengo Nagashima 3 Seiichiro Sakao 1 Koichiro Tatsumi 1 Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; 2Department of Respiratory and Sleep Medicine, Fukuoka University School of Medicine, Fukuoka, Japan; 3Research Center for Medical and Health Data Science, The Institute of Statistical Mathematics, Tokyo, Japan 1 Purpose: Although patients with suspected obstructive sleep apnea (OSA) might suffer difficulty in falling asleep during overnight polysomnography (PSG), standard hypnotics to obtain sleep during PSG have not been established. The aim of this study was to investigate the safety and efficacy of a new hypnotic agent, suvorexant, a dual orexin receptor antagonist, for insomnia in suspected OSA patients during in-laboratory PSG. Patients and methods: An observational study was conducted during PSG for 149 patients with suspected OSA who had no insomnia at home. Patients with difficulty in falling asleep during PSG were optionally permitted to take single-use suvorexant. Patients with residual severe insomnia (.1 hour) after taking suvorexant were permitted to take an add-on use zolpidem. Clinical data and sleep questionnaire results were analyzed between a no insomnia group (without hypnotics) and an insomnia group (treated with suvorexant). Results: Among 84 patients who experienced insomnia during PSG and required hypnotics (the insomnia group; treated with suvorexant), 44 (52.4%) achieved sufficient subjective sleep with single-use of suvorexant, while the other 40 (47.6%) required suvorexant plus zolpidem. An apnea hypopnea index (AHI) of $5 was observed in 144 out of 149 patients with predominantly obstructive respiratory events. Among those patients, 70.8% in the no insomnia group and 63.1% in the insomnia group had severe OSA. Regarding both subjective sleep time and morning mood, significant differences between the no insomnia group and the insomnia group were not observed. No patient taking suvorexant had an adverse event, such as delirium or falling. Conclusion: Single-use suvorexant seems to be a safe and effective (but mild) hypnotic agent for suspected OSA patients with insomnia during in-laboratory PSG. Keywords: insomnia, suvorexant, polysomnography, obstructive sleep apnea, zolpidem, natural sleep Introduction Correspondence: Jiro Terada Department of Respirology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, chuo-ku, Chiba city, Chiba, Japan Tel +81 43 222 7171 Fax +81 43 226 2176 Email 809 submit your manuscript | www.dovepress.com Drug Design, Development and Therapy 2019:13 809–816 Dovepress © 2019 Matsumura et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php). http://dx.doi.org/10.2147/DDDT.S197237 Powered by TCPDF (www.tcpdf.org) In-laboratory overnight polysomnography (PSG) has been still widely conducted as a gold standard test to diagnose obstructive sleep apnea (OSA). Although most patients with suspected OSA can undergo PSG with substantial sleep due to the symptom of severe sleepiness, some patients suffer difficulty in falling asleep during PSG. This insomnia is partly explained by a “first-night effect” of PSG recordings, a well-known phenomenon caused by discomfort with the PSG electrode cables, limitation of movement, and/or maladaptation to the unfamiliar circumstances of a sleep laboratory,1,2 especially in anxiety disorders patients and older patients.3,4 Because the first-night Dovepress Drug Design, Development and Therapy downloaded from https://www.dovepress.com/ by 88.198.20.149 on 18-Oct-2019 For personal use only. Matsumura et al effect causes a decrease in total sleep time (TST), frequent nocturnal awakening, and disruption of sleep structure (eg, increased stage N1 sleep, reduced rapid eye movement [REM] sleep, and longer REM latency),5 more adequate amount of natural sleep during the sleep test is preferred. However, conducting PSG on multiple nights seems impractical due to the cost benefit, patient burden, and limited resources. Additionally, the use of an ideal hypnotic agent to mitigate insomnia during PSG has not been standardized. Benzodiazepines and/or non-benzodiazepines (ie, type A gamma-aminobutyric acid [GABAA] receptor hypnotic agents) are most frequently used to treat insomnia worldwide, even during hospitalization.6 However, there are several concerns about the routine use of GABAA receptor agonists for patients with insomnia who might have undiagnosed OSA. First, benzodiazepines have the potential to decrease upper airway muscle activity and ventilatory responses to carbon dioxide, which could confound the disease state of sleep apnea.7–9 Although both benzodiazepines and non-benzodiazepines did not increase apnea index in patients with mild-to-moderate OSA,10,11 the effects of GABAA receptor hypnotic agents in patients with severe OSA is yet unknown. Second, GABAA receptor hypnotic agents can be occasionally associated with delirium and falling, which may cause bone fractures, especially in elderly patients.12–14 Third, benzodiazepines are known to disrupt natural sleep architecture by decreasing slow wave sleep and REM sleep, and non-benzodiazepines are controversially reported to reduce REM sleep.15,16 In 2014, the US Food and Drug Administration (FDA) approved suvorexant (Merck & Co., Inc., Whitehouse Station, NJ, USA), a new class of hypnotic agent, which blocks both orexin receptor type 1 and 2, for the treatment of insomnia with sleep onset and/or sleep maintenance difficulties. Since orexin is a neuropeptide that promotes wakefulness and affects the sleep–wake cycle,17,18 this orexin receptor antagonist can represent a novel approach to treat insomnia; current benzodiazepine receptor agonists appear to promote sleep by (...truncated)