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Ann Thorac Med. 2019 Jan-Mar;14(1):49-55. doi: 10.4103/atm.ATM_198_18.

The effect of nonbenzodiazepines sedative hypnotics on apnea-hypopnea index: A meta-analysis.

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Department of Medicine and Sleep Medicine, Clay County Hospital, Flora, Illinois, USA.
Division of Otolaryngology, Sleep Surgery and Sleep Medicine, Tripler Army Medical Center, Honolulu, Hawaii, USA.
Astria Health Center, Euclid, Grandview, Washington, USA.



Nonbenzodiazepine (non-BZD) sedative hypnotics (NBSH) refer to non-BZD sedatives that act as BZD receptor agonists such as zolpidem, zaleplon, and eszopiclone. Today, there is a high prevalence of insomnia with or without concurrent obstructive sleep apnea (OSA). Our goal was to study how NBSH use impacts the baseline apnea-hypopnea index (AHI) in patients with or without OSA.


PubMed/MEDLINE, Scopus, Web of Science and Cochrane Library databases were searched.


Seventeen studies comprising a cumulative total of 2099 patients were identified in the last 30 years (between 1988 and 2017) that evaluated the effect of NBSH on respiratory parameters during sleep. The AHI mean (M) ± standard deviation (SD) in NBSH group was 13.17 ± 16.27 versus 15.94 ± 19.31 (mean difference [MD]-95% confidence interval [CI], 2.77 [1.463-4.076]). Six studies (100 patients) compared zolpidem with either placebo or no medication and demonstrated an AHI MD of -0.61 events/h (95% CI - 1.94, 0.71), overall effect Z = 0.9, P = 0.36. Four studies (362 patients) compared eszopiclone with placebo and demonstrated an AHI MD of -5.73 events/h0 (95% CI - 8.90, -0.2.57). Two large studies (979 patients) compared both zolpidem and eszopiclone to no medication and found AHI MD of -1.66 events/h (95% CI - 5.87, 0.2.55).


The majority of patients using NBSH did not develop any worsening of existing AHI, when using NBSH, regardless of their baseline AHI values (mild, moderate, severe, or no OSA). On average, the AHI improved minimally with NBSH and eszopiclone showed the largest difference in AHI with an MD of -5.73 events/h.


Apnea–hypopnea index; continuous positive airway pressure; eszopiclone; nonbenzodiazepine sedative hypnotics; obstructive sleep apnea; placebo; zolpidem; zopiclone

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