What is the next medication recommendation for insomnia in a patient taking trazodone 150 mg for sleep, which is not effective, and also taking Percocet (oxycodone) PRN, with a history of obstructive sleep apnea managed with Continuous Positive Airway Pressure (CPAP)?

Next Medication Recommendation for Refractory Insomnia with OSA

Discontinue trazodone and initiate cognitive behavioral therapy for insomnia (CBT-I) as first-line treatment, followed by low-dose eszopiclone (1-2 mg) or zolpidem (5 mg) if pharmacotherapy is necessary, while avoiding benzodiazepines and opioids due to respiratory depression risk in obstructive sleep apnea. 1, 2, 3

Why Trazodone Should Be Discontinued

The VA/DOD guidelines explicitly advise against trazodone for chronic insomnia disorder due to its unfavorable benefit-risk profile. 1, 2

• Systematic reviews demonstrate no significant differences between trazodone (50-150 mg) and placebo in sleep efficiency, sleep onset latency, total sleep time, or wake after sleep onset 1, 2
• While trazodone showed modest improvement in subjective sleep quality only, the low-quality evidence supporting its efficacy is outweighed by its adverse effect profile 1, 2
• The patient is already on 150 mg (the upper end of studied doses) without benefit, making dose escalation inappropriate 1, 4
• Trazodone's adverse effects include daytime drowsiness, dizziness, and psychomotor impairment—particularly concerning in patients with OSA who may already have daytime sleepiness 5, 6

Critical Safety Concern: Percocet and OSA

The concurrent use of Percocet (oxycodone) with OSA represents a dangerous combination that must be addressed immediately. 1

• Opioids cause respiratory depression and worsen OSA severity, increasing risk of hypoventilation 1
• The combination of sedating medications (trazodone + opioids) creates additive respiratory suppression risk 2
• Strongly recommend discussing opioid alternatives or tapering with the prescribing provider 1

First-Line Treatment: Cognitive Behavioral Therapy for Insomnia

CBT-I should be the initial treatment for chronic insomnia, especially in patients with comorbid OSA. 2, 5, 3

• CBT-I is effective and durable without respiratory concerns 2, 3
• Components include stimulus control therapy, sleep restriction therapy, and cognitive therapy 2
• CBT-I may increase CPAP adherence in patients with comorbid insomnia and OSA 3
• Insomnia often reduces PAP therapy acceptance, and treating it can improve OSA outcomes 3

Pharmacotherapy Options If CBT-I Insufficient

Preferred First-Choice Medications:

Non-benzodiazepine receptor agonists (Z-drugs) are recommended as second-line pharmacotherapy, with careful dosing in OSA patients. 2, 5

Eszopiclone (Preferred Option):

• Recommended for both sleep onset and sleep maintenance insomnia 2
• Start at 1 mg (lower than standard 2-3 mg) given OSA and concurrent sedating medication history 7
• Take immediately before bed with 7-8 hours available for sleep 7
• Avoid taking with or after meals to maximize effectiveness 7
• Monitor for next-day drowsiness and complex sleep behaviors 7

Zolpidem (Alternative Option):

• Start at 5 mg (not 10 mg) given OSA and female patients have lower clearance 8
• Take immediately before bedtime with at least 7-8 hours remaining before awakening 8
• The 10 mg dose increases risk of next-day impairment of driving and activities requiring full alertness 8
• Do not readminister during the same night 8

Low-Dose Doxepin (3-6 mg):

• Recommended specifically for sleep maintenance insomnia with less respiratory concern than other sedating antidepressants 2, 5
• May be preferable if middle-of-night or early morning awakening is the primary complaint 2

Ramelteon:

• Appropriate for sleep onset insomnia with minimal respiratory effects 2, 5
• Melatonin receptor agonist with favorable safety profile in OSA 5

Medications to Absolutely Avoid:

Benzodiazepines are contraindicated due to known risk of hypoventilation in patients with respiratory conditions including sleep apnea. 1, 5

• Despite improving sleep parameters, the harms substantially outweigh benefits 1
• Risk for dependency, falls, cognitive impairment in older patients, and respiratory depression 1

Antihistamines and antipsychotics are not recommended for chronic insomnia. 1, 2

• Tolerance to sedative effects of antihistamines develops after 3-4 days 1
• Beers Criteria strongly recommend avoiding antihistamines in older adults 1
• Antipsychotics (including quetiapine) have sparse evidence and known harms 1

Over-the-counter supplements (melatonin, valerian, chamomile, kava) are not supported by evidence. 1

Implementation Algorithm

1. Immediately address Percocet use: Coordinate with prescribing provider regarding opioid risks in OSA 1

2. Discontinue trazodone 150 mg given lack of efficacy and guideline recommendations against its use 1, 2, 5

3. Refer for CBT-I as first-line treatment 2, 5, 3

4. If pharmacotherapy needed while awaiting CBT-I or if CBT-I insufficient:

   • Start eszopiclone 1 mg OR zolpidem 5 mg at bedtime 2, 7, 8
   • Use lowest effective dose for shortest duration 2, 5
   • Ensure CPAP compliance is optimized, as untreated OSA can worsen insomnia 3

5. Follow-up within 1-2 weeks to assess effectiveness, side effects, and next-day impairment 2

6. Counsel patient on:

   • Taking medication only when able to get 7-8 hours of sleep 7, 8
   • Risk of complex sleep behaviors (sleep-walking, sleep-driving) 7
   • Avoiding alcohol and other sedating medications 7, 8
   • Not driving or operating machinery until fully awake the next day 7, 8

Common Pitfalls to Avoid

• Do not increase trazodone dose—the patient is already at the upper limit of studied doses without benefit 1, 2
• Do not prescribe benzodiazepines despite their sleep-promoting effects, given respiratory contraindication 1, 5
• Do not ignore the opioid-OSA interaction—this combination significantly increases mortality risk 1
• Do not use standard dosing of Z-drugs—start lower in OSA patients and those with history of sedating medication use 5, 7, 8
• Do not neglect CPAP optimization—poor CPAP adherence can perpetuate insomnia 3