Doxepin for Insomnia in Patients with Alcohol Use Disorder
Doxepin (3-6 mg) is a reasonable second-line pharmacological option for sleep maintenance insomnia in patients with AUD, but only after implementing Cognitive Behavioral Therapy for Insomnia (CBT-I) as first-line treatment and explicitly avoiding benzodiazepines and benzodiazepine receptor agonists due to their cross-tolerance with alcohol and high relapse risk. 1, 2
Treatment Algorithm for Insomnia in AUD
Step 1: First-Line Treatment - CBT-I (Mandatory Initial Approach)
CBT-I must be initiated before or alongside any pharmacotherapy in patients with AUD and insomnia, as it demonstrates large reductions in insomnia severity (ISI reduction of -5.51 points post-treatment) that persist at 6-month follow-up (ISI reduction of -4.55 points) across the spectrum of AUD. 3
CBT-I also reduces alcohol-related problems through its effect on insomnia severity, making it uniquely suited for this dual-diagnosis population. 4
CBT-I components include stimulus control therapy, sleep restriction therapy, relaxation techniques, and sleep hygiene education—delivered individually, in groups, via telephone, web-based modules, or self-help books. 1
Critical timing consideration: CBT-I should NOT be delayed until abstinence is established; it is effective and appropriate early in AUD treatment regardless of current drinking status. 4
Step 2: Pharmacological Options When CBT-I is Insufficient or Unavailable
Medications to Consider:
Low-dose doxepin (3-6 mg) is specifically recommended for sleep maintenance insomnia and represents a safer option than benzodiazepines in this population. 1
Mirtazapine has moderate evidence for treating insomnia in AUD and simultaneously addresses comorbid depression/anxiety if present. 5
Gabapentin immediate-release has moderate evidence for insomnia in AUD. 5
Quetiapine has moderate evidence but should be reserved for cases with insufficient response to safer alternatives due to concerns about metabolic side effects, weight gain, and neurological effects. 2, 5
Trazodone has low evidence in the AUD population and is not recommended by general insomnia guidelines, though it has been used off-label extensively. 2, 5
Medications to Explicitly Avoid:
Benzodiazepines and benzodiazepine receptor agonists (zolpidem, eszopiclone, zaleplon, temazepam) are contraindicated in AUD patients due to cross-tolerance with alcohol, significant risk of dependence, tolerance development, and increased relapse risk. 2
Antihistamines (diphenhydramine) lack efficacy data and carry anticholinergic side effects. 2
Ramelteon and suvorexant, while first-line for general insomnia, have insufficient evidence specifically in the AUD population, though suvorexant is under investigation for this indication. 6
Step 3: Specific Doxepin Prescribing Details
Dosing: 3-6 mg at bedtime, specifically for sleep maintenance insomnia (not sleep onset). 1
Mechanism: At these low doses, doxepin acts primarily as a histamine H1 receptor antagonist with minimal anticholinergic or adrenergic effects.
Duration: Use the lowest effective dose for the shortest duration possible, with regular reassessment. 1
Monitoring: Assess effectiveness and side effects during initial treatment period, with periodic reassessment to avoid long-term continuation without clinical justification. 1
Critical Clinical Considerations
Addressing Alcohol as Self-Medication
Patients who use alcohol to help fall asleep have a higher risk of relapse after stopping treatment—this requires explicit counseling and close monitoring. 5
Abstinence or decreased alcohol use may independently improve insomnia symptoms, creating a positive feedback loop when combined with proper insomnia treatment. 5
Comorbid Psychiatric Conditions
- If comorbid depression or anxiety is present, sedating antidepressants (mirtazapine, low-dose doxepin at higher doses than used for insomnia) become preferred as they simultaneously address both conditions. 1
Timing of Pharmacotherapy
CBT-I may take several weeks to be effective; pharmacological treatments like doxepin could be proposed to patients with severe symptoms or psychiatric comorbidities during this initial period. 5
Short-term hypnotic treatment should always be supplemented with behavioral and cognitive therapies, never used as monotherapy. 1
Common Pitfalls to Avoid
Using benzodiazepines or Z-drugs (zolpidem, eszopiclone) in AUD patients—these are cross-tolerant with alcohol and dramatically increase relapse risk. 2
Prescribing doxepin for sleep onset insomnia—it is specifically indicated only for sleep maintenance problems. 1
Delaying CBT-I until abstinence is achieved—this outdated approach denies patients the most effective treatment when they need it most. 4
Continuing pharmacotherapy long-term without periodic reassessment—all sleep medications should be regularly evaluated for ongoing necessity. 1
Failing to educate patients about treatment goals, realistic expectations, safety concerns, and the importance of behavioral treatments alongside any medication. 1