Can you use trazodone while on Continuous Positive Airway Pressure (CPAP) therapy for sleep apnea?

Trazodone Use with CPAP for Sleep Apnea

Trazodone should generally be avoided in patients with obstructive sleep apnea, even when using CPAP therapy, as major clinical practice guidelines advise against its use for sleep disorders in this population due to insufficient efficacy evidence and concerning adverse effects. 1

Guideline-Based Recommendations

The 2019 VA/DOD Clinical Practice Guidelines explicitly recommend against the use of trazodone for treatment of chronic insomnia disorder, including in patients with comorbid sleep apnea. 1 This recommendation stems from:

• Lack of efficacy: Systematic reviews found no differences in sleep efficiency or discontinuation rates due to adverse events between trazodone (50-150 mg) and placebo in patients with chronic insomnia. 1
• Minimal sleep benefits: While trazodone improved subjective sleep quality, it showed no differences in objective measures including sleep onset latency, total sleep time, or wake after sleep onset. 1
• Adverse effect profile: The low-quality evidence supporting trazodone's efficacy was deemed insufficient to outweigh its adverse effects. 1
• Increased arousals: A small randomized controlled trial demonstrated that trazodone actually increased arousals during sleep in OSA patients. 1

Physiological Effects on Sleep Apnea

Research evidence reveals complex and potentially problematic effects of trazodone in OSA patients:

• Arousal threshold changes: Trazodone increases the respiratory arousal threshold by approximately 32% in OSA patients with low arousal thresholds, which theoretically could worsen apnea duration. 2, 3
• No improvement in AHI: Despite raising arousal thresholds, trazodone does not reduce the apnea-hypopnea index (39 ± 12 vs 39 ± 11 events/hour; P = 0.94). 2
• Preserved upper airway function: Trazodone does not systematically impair dilator muscle activity or worsen upper airway collapsibility, which is somewhat reassuring. 2
• Insufficient therapeutic benefit: The magnitude of arousal threshold change was inadequate to overcome compromised upper airway anatomy in OSA patients. 2

Clinical Decision Algorithm

If a patient on CPAP has comorbid insomnia or depression requiring pharmacotherapy:

1. First-line approach: Optimize CPAP adherence through educational, behavioral, and troubleshooting interventions rather than adding sedating medications. 1

2. For persistent insomnia despite CPAP optimization: Consider low-dose doxepin (3-6 mg) or non-benzodiazepine benzodiazepine receptor agonists (e.g., eszopiclone) as these have better evidence profiles than trazodone. 1

3. For comorbid depression: Use non-sedating SSRIs (e.g., fluoxetine, sertraline) at therapeutic doses rather than relying on sedating antidepressants like trazodone for dual sleep/mood effects. 4

4. Avoid trazodone specifically because guidelines explicitly recommend against it, and research shows it increases arousals without improving AHI. 1

Critical Caveats

• CPAP remains essential: No pharmacologic agent, including trazodone, should replace CPAP as the primary OSA treatment, as CPAP demonstrates superior efficacy in reducing AHI, arousal index, and oxygen desaturation. 1, 5

• Benzodiazepines are worse: While trazodone is not recommended, benzodiazepines pose even greater risks in OSA patients, including hypoventilation, falls, cognitive impairment, and dependency. 1

• Weight considerations: If antidepressants are necessary, avoid mirtazapine as it causes significant weight gain that can worsen OSA severity. 1

• Historical use is not evidence: The fact that trazodone has been used historically in some epilepsy patients with sleep apnea 6 does not constitute sufficient evidence for routine use, especially given current guideline recommendations against it.

Monitoring Requirements if Trazodone is Already Prescribed

If a patient is already taking trazodone when diagnosed with OSA:

• Strongly consider discontinuation and switching to guideline-concordant alternatives. 1
• If continuation is deemed necessary, ensure optimal CPAP adherence with objective monitoring of usage data and efficacy. 1
• Monitor for worsening daytime sleepiness, increased arousal frequency, or reduced sleep quality. 1
• Consider repeat polysomnography to assess whether trazodone is affecting OSA severity or CPAP effectiveness. 4