What is the relationship between obstructive sleep apnea (OSA) and benzodiazepine use?

From the Guidelines

Benzodiazepines should generally be avoided in patients with sleep apnea due to their potential to worsen the condition, as evidenced by their depressive effects on the central nervous system, relaxation of upper airway muscles, and reduction of respiratory drive 1. Benzodiazepines like diazepam, lorazepam, and alprazolam can exacerbate sleep apnea by:

• Depressing the central nervous system
• Relaxing upper airway muscles
• Reducing respiratory drive These effects can increase the frequency and duration of apnea episodes, potentially leading to more severe oxygen desaturation during sleep. If a benzodiazepine is deemed necessary:
• Choose a shorter-acting option like oxazepam or lorazepam
• Start with the lowest possible dose (e.g., lorazepam 0.5 mg)
• Use intermittently rather than nightly
• Monitor closely for worsening of sleep apnea symptoms Alternative medications to consider for anxiety or insomnia in sleep apnea patients include:
• Non-benzodiazepine sleep aids (e.g., zolpidem, at a low dose of 5 mg) 1
• Melatonin (3-5 mg at bedtime)
• Certain antidepressants (e.g., trazodone 25-50 mg at bedtime) Always ensure proper sleep apnea treatment (e.g., CPAP) is optimized before considering sedative medications, as supported by the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guidelines 1. Cognitive behavioral therapy for insomnia (CBT-I) should be considered as a first-line, non-pharmacological approach for sleep issues in these patients.

From the Research

Relationship Between Obstructive Sleep Apnea (OSA) and Benzodiazepine Use

• The relationship between OSA and benzodiazepine use is complex, with some studies suggesting that benzodiazepines may worsen sleep-related breathing disorders, especially in patients with chronic obstructive pulmonary disease or cardiac failure 2.
• However, other studies have found that benzodiazepines may not significantly worsen OSA in patients with mild to moderate disease 3, 4.
• Some benzodiazepines, such as eszopiclone and sodium oxybate, may even have a beneficial effect on OSA, with significant decreases in apnea-hypopnea index (AHI) observed in some studies 3.
• Nevertheless, caution is required when prescribing benzodiazepines to patients with OSA, especially outside the severity of the OSA cohorts and the corresponding dose of compounds given in the particular studies 3.
• There is also evidence to suggest that long-term use of benzodiazepines can lead to new onset central sleep apnea, which can mask pre-existing OSA 5.
• The effects of benzodiazepines on OSA may vary depending on the specific drug, dose, and individual patient characteristics, highlighting the need for further research in this area 6, 3.

Key Findings

• A study of 14 patients with mild to moderate OSA found that nitrazepam did not significantly worsen sleep apnea, although there was individual variability in response to the drug 4.
• A review of 14 studies examining the effects of sedative and hypnotic drugs on OSA found that none of the drugs produced a significant increase in AHI or oxygen desaturation index (ODI) 3.
• However, some studies have reported significant decreases in minimum nocturnal peripheral capillary oxygen saturation (SpO2) with certain benzodiazepines, such as zolpidem and triazolam 3.