Cited by 62Sleep and related disordersPharmacovigilance and Adverse Drug ReactionsObstructive Sleep Apnea Research

Meta-Analyses of Hypnotics and Infections: Eszopiclone, Ramelteon, Zaleplon, and Zolpidem

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Joya, Florendo L., Kripke, Daniel F., Loving, Richard T., Dawson, Arthur, Kline, Lawrence E.·2009·Journal of Clinical Sleep Medicine

Abstract

Study objectives Recent meta-analyses raising concern about risks of hypnotics suggest a need for more clarification of these risks.Methods Because of preliminary suggestions that eszopiclone causes infections, we studied US Food and Drug Administration files on the 4 most-recently approved hypnotics, combined with published studies, to compile the risk ratios of infections for groups randomly assigned to receive hypnotics versus those assigned to receive placebos in controlled trials. Parallel controlled clinical trials of eszopiclone, ramelteon, zaleplon, and zolpidem were included when data on subjects, duration of exposure, and adverse effects were available. Results of trials were combined by meta-analyses.Results Of 8828 participants assigned to the 4 hypnotics and 4383 participants who randomly received placebos, 606 in the hypnotics groups and 200 in the placebo groups were reported to develop some kind of infection (risk ratio = 1.44, 95% confidence interval 1.25-1.64, p < 0.00001). Most infections were apparently mild and did not lead to dropouts. Subanalyses for individual drugs indicated that eszopiclone and zolpidem individually were associated with reported infections. There were insufficient data concerning individual studies of zaleplon and ramelteon for valid secondary meta-analyses of zaleplon or ramelteon by themselves.Conclusions Research is needed to objectively determine whether the use of hypnotics increases the risk of infections. Immune compromise or esophageal reflux and aspiration should be studied as possible mechanisms.

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  1. Barbero GJ. Gastroesophageal reflux and upper airway disease. Otolaryngol Clin North Am 1996;29:27-38.
  2. The Nordic Cochrane Center. Review Manager 5.0.14. Copenha- gen, Cochrane Collaboration, 2008.

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Authors
Joya, F. L., Kripke, D. F., Loving, R. T., Dawson, A., & Kline, L. E.
Affiliations
Scripps Clinic (US)
Corresponding author
Kripke, Daniel F.
Venue
Journal of Clinical Sleep Medicine
Published
2009-08-15
Volume
5
Issue
4
Pages
377-383
ISSN
  • 1550-9389 (ISSN-L)
  • 1550-9397
OpenAlex
W147714449
Cited by
62
References
25
Citations by year
2026: 1 · 2024: 3 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 6 · 2016: 7 · 2015: 9 · 2014: 5 · 2013: 2 · 2012: 3
FWCI
2.54
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Sleep Medicine (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
  • Health Sciences › Medicine › Physiology › Obstructive Sleep Apnea Research
Keywords
hypnotics, infection, eszopiclone, ramelteon, zaleplon, zolpidem, adverse drug reactions, drug safety, immune compromise, gastroesophageal reflux, drug exposure duration
MeSH terms
Eszopiclone, Zolpidem, Acetamides, Humans, Hypnotics and Sedatives, Indenes, Infections, Piperazines, Pyridines, Pyrimidines, Risk, Randomized Controlled Trials as Topic, Azabicyclo Compounds

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