What sleep medication is appropriate for an adult patient receiving buprenorphine/naloxone (Suboxone) for opioid use disorder with insomnia?

Sleep Medication for Patients on Suboxone

For adults receiving buprenorphine/naloxone (Suboxone) for opioid use disorder with insomnia, low-dose doxepin 3–6 mg at bedtime is the preferred first-line pharmacologic option, combined with Cognitive Behavioral Therapy for Insomnia (CBT-I). 1

Why Low-Dose Doxepin is Optimal

• Low-dose doxepin (3–6 mg) reduces wake after sleep onset by 22–23 minutes and increases total sleep time by 26–32 minutes with minimal side effects and no abuse potential – critical for patients with opioid use disorder. 1, 2

• At hypnotic doses (3–6 mg), doxepin exhibits minimal anticholinergic activity and works through selective H₁-histamine receptor antagonism, avoiding the broader tricyclic effects seen at higher doses. 1, 2

• Doxepin carries zero addiction risk, making it uniquely appropriate for patients in recovery from substance use disorder, unlike benzodiazepines or Z-drugs. 1, 2

• Insomnia is highly prevalent (approximately 60%) in adults receiving buprenorphine for OUD and is associated with worse treatment outcomes, depression, anxiety, and post-traumatic stress. 3

Mandatory Behavioral Therapy Component

• CBT-I must be initiated concurrently with any sleep medication because it provides superior long-term efficacy and sustained benefits after medication discontinuation, whereas pharmacotherapy effects wane once stopped. 1, 4

• Core CBT-I components include stimulus control (use bed only for sleep), sleep restriction (limit time in bed to actual sleep time plus 30 minutes), relaxation techniques, and cognitive restructuring of negative sleep beliefs. 1, 4

• Sleep hygiene alone is insufficient as monotherapy but should supplement other CBT-I components: maintain consistent sleep-wake times, avoid caffeine ≥6 hours before bed, eliminate screens ≥1 hour before bedtime, and keep the bedroom quiet and temperature-regulated. 1

Dosing and Implementation

• Start doxepin 3 mg at bedtime; if insufficient after 1–2 weeks, increase to 6 mg. 1, 2

• Take within 30 minutes of bedtime with at least 7–8 hours remaining before planned awakening. 1

• Reassess after 1–2 weeks to evaluate effects on sleep-onset latency, total sleep time, nocturnal awakenings, and daytime functioning; monitor for adverse effects (somnolence, headache). 1, 2

• FDA approval is for short-term use (4–5 weeks), though studies demonstrate maintained efficacy up to 12 weeks. 2

Alternative Second-Line Options (if doxepin fails or is contraindicated)

• Ramelteon 8 mg is a melatonin-receptor agonist with no abuse potential, no DEA scheduling, and no withdrawal symptoms – making it the only other truly non-addictive option appropriate for patients with substance use history. 1

• Suvorexant 10 mg (orexin-receptor antagonist) reduces wake after sleep onset by 16–28 minutes and carries lower risk of cognitive/psychomotor impairment than benzodiazepine-type agents. 1

• Eszopiclone 2–3 mg improves both sleep onset and maintenance (increases total sleep time by 28–57 minutes), but carries higher risk of complex sleep behaviors, falls, and cognitive impairment compared to doxepin. 1, 5

Medications to Explicitly AVOID in Patients on Suboxone

• Traditional benzodiazepines (lorazepam, clonazepam, diazepam) are absolutely contraindicated due to high risk of respiratory depression when combined with buprenorphine, plus dependence, falls, cognitive impairment, and associations with dementia and fractures. 1, 6

• Trazodone is explicitly NOT recommended – yields only ~10 minutes reduction in sleep latency with no improvement in subjective sleep quality; adverse events occur in ~75% of older adults. 1, 2

• Over-the-counter antihistamines (diphenhydramine, doxylamine) are NOT recommended due to lack of efficacy data, strong anticholinergic effects (confusion, urinary retention, falls), and tolerance development within 3–4 days. 1

• Antipsychotics (quetiapine, olanzapine) should NOT be used for primary insomnia due to weak evidence and significant risks including weight gain, metabolic dysregulation, extrapyramidal symptoms, and increased mortality in elderly with dementia. 1, 6

• Melatonin supplements are NOT recommended – produce only ~9 minutes reduction in sleep latency with insufficient evidence of efficacy. 1, 6

Critical Safety Considerations for Buprenorphine Patients

• Buprenorphine/naloxone is generally well tolerated; common adverse effects include anxiety, constipation, dizziness, drowsiness, headache, nausea, and sedation – adding sedating medications requires careful monitoring. 7, 8

• Combining multiple CNS depressants (buprenorphine + benzodiazepines or Z-drugs) markedly increases risk of respiratory depression, cognitive impairment, falls, and complex sleep behaviors – avoid polypharmacy. 1

• Buprenorphine treatment itself improves sleep quality over 4 months (PSQI scores decrease from 8.87 to 6.85), though sleep problems remain prevalent. 9

• Patients with OUD and insomnia report that poor sleep interferes with their OUD treatment and that improved sleep would assist with recovery. 3

Common Pitfalls to Avoid

• Starting hypnotic therapy without first implementing CBT-I leads to less durable benefit and missed opportunity for non-pharmacologic intervention. 1

• Using benzodiazepines or Z-drugs in patients with substance use history creates dangerous polypharmacy and high relapse/diversion risk. 1, 6

• Prescribing trazodone because it is perceived as "safer" despite explicit guideline recommendations against its use for insomnia. 1, 2

• Failing to reassess pharmacotherapy regularly (every 2–4 weeks) to evaluate efficacy, side effects, and continued need; taper after 3–6 months if effective. 1

• Continuing hypnotic therapy long-term without periodic reassessment – FDA labeling indicates short-term use; routine use beyond 4 weeks requires strong justification. 1, 5