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Hypnotics on Obstructive Sleep Apnea Severity and Endotypes: A Systematic Review and Meta-Analysis
Ludovico Messineo1, Scott A Sands1, Gonzalo Labarca1,2
1Division of Sleep and Circadian Disorders, Department of Medicine, and Department of Neurology, Brigham & Women's Hospital and Harvard Medical School, Boston, Massachusetts; and.
Summary
Common hypnotics minimally increase arousal threshold but do not improve obstructive sleep apnea (OSA) severity. Further research into hypnotics for OSA is discouraged, except for specific patient groups.
Area of Science:
- Sleep Medicine
- Pharmacology
- Respiratory Medicine
Background:
- Obstructive sleep apnea (OSA) is often linked to low arousal threshold and poor muscle responsiveness.
- Hypnotics were investigated for their potential to treat OSA by increasing arousal threshold and genioglossus responsiveness.
Purpose of the Study:
- To evaluate the impact of common hypnotics on arousal threshold, OSA severity, and genioglossus responsiveness.
- To assess the association between changes in arousal threshold and apnea-hypopnea index (AHI) post-treatment.
Main Methods:
- Meta-analysis of randomized clinical trials sourced from MEDLINE, Embase, CENTRAL, and ClinicalTrials.gov.
- Individual patient data meta-analysis to explore the relationship between arousal threshold changes and AHI.
- Quality of evidence (QoE) assessed using the Grades of Recommendation Assessment, Development and Evaluation (GRADE) system.
Main Results:
- Hypnotics showed a minimal increase in arousal threshold (2.7 cm H2O pressure swings; moderate QoE) but did not significantly alter OSA severity (-1.4 events/h; moderate QoE).
- No overall association was found between arousal threshold changes and AHI reduction.
- Modest AHI reductions (∼10%) were observed in individuals with a very low arousal threshold or a 0-25% increase in arousal threshold from placebo; genioglossus responsiveness remained unaffected (high QoE).
Conclusions:
- Clinical use or further research of hypnotics as standalone OSA treatments is generally not recommended.
- Exceptions include patients with comorbid insomnia or those with a very low arousal threshold, potentially benefiting from combination therapy.
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