What is the next best treatment approach for a 32-year-old female patient in remission from alcohol use disorder, presenting with anxiety, depression, insomnia, and withdrawal symptoms, currently taking propanolol (propranolol) with a history of ineffective trials of gabapentin, Lexapro (escitalopram), Zoloft (sertraline), and Valium (diazepam)?

Treatment Recommendation for Alcohol Use Disorder in Remission with Anxiety, Depression, and Insomnia

Given this patient's history of alcohol use disorder in remission with persistent withdrawal symptoms, anxiety, depression, and insomnia, combined with failed trials of multiple medications, I recommend initiating cognitive behavioral therapy for insomnia (CBT-I) as the primary intervention, combined with a trial of mirtazapine 7.5-30 mg at bedtime for its dual benefits on sleep and depression, while avoiding benzodiazepines given her substance use history. 1

Rationale and Clinical Approach

Why Avoid Benzodiazepines Despite Previous Valium Use

• Benzodiazepines carry significant risk of dependence in patients with alcohol use disorder, with approximately 50% of patients prescribed benzodiazepines using them continuously for at least 12 months, a practice not recommended by clinical guidelines 1
• Benzodiazepines share cross-tolerance with alcohol and increase risk of relapse, respiratory depression when combined with other sedatives, and withdrawal symptoms upon discontinuation 1, 2
• The benzodiazepine withdrawal syndrome itself includes sleep disturbance, anxiety, panic attacks, tremor, and perceptual changes—symptoms this patient is already experiencing 2
• While diazepam is effective for acute alcohol withdrawal, it should not be used for ongoing anxiety or insomnia management in patients with alcohol use disorder in remission 3, 4

First-Line Non-Pharmacologic Intervention

Cognitive Behavioral Therapy for Insomnia (CBT-I) should be the foundation of treatment:

• CBT-I is recommended as standard therapy and includes multicomponent approaches: cognitive therapy, stimulus control, sleep restriction with or without relaxation therapy 1
• Sleep hygiene alone is insufficient but should be combined with other therapies 1
• When initial psychological/behavioral treatment has been ineffective (as with this patient's poor functioning), combination CBT-I therapies or combined treatments should be considered 1

Pharmacologic Recommendation: Mirtazapine

Mirtazapine offers multiple advantages for this patient's symptom cluster:

• Mirtazapine has a significantly faster onset of action than SSRIs (which this patient has already failed), with effects seen before the typical 4-week response time 1
• It addresses three core problems simultaneously: insomnia, depression, and anxiety 1
• Mirtazapine 7.5-30 mg at bedtime is specifically recommended for insomnia in palliative care guidelines 1
• It has been shown to be safe in patients with comorbid conditions, though efficacy data specifically for depression in complex cases is limited 1
• Mirtazapine is not associated with dependence risk, unlike benzodiazepines or gabapentinoids 1

Why Not Restart or Continue Other Failed Medications

Gabapentin should be avoided:

• Gabapentinoids (gabapentin, pregabalin) carry dependence and withdrawal risks similar to benzodiazepines 1
• Approximately 50% of patients prescribed gabapentinoids use them continuously for at least 12 months 1
• The patient has already failed a trial of gabapentin [@question context]
• Gabapentin has shown poor efficacy as substitution therapy even for pregabalin use disorder [@12@]

SSRIs (Lexapro/escitalopram, Zoloft/sertraline) considerations:

• The patient has already failed trials of both medications [@question context]
• While sertraline combined with CBT showed modest benefit in depressed alcoholics, the patient has already tried this without success 5
• Second-generation antidepressants show similar efficacy for depression with accompanying anxiety and insomnia, with no clear superior choice after SSRI failure 1
• When switching after SSRI failure, the STAR*D trial showed that 1 in 4 patients became symptom-free when switching to bupropion, sertraline, or venlafaxine, with no difference among the three 1

Propranolol (current medication):

• Beta blockers like propranolol are not recommended for social anxiety disorder based on negative evidence 1
• Propranolol alone is insufficient for this patient's complex presentation [@question context]

Alternative Pharmacologic Options if Mirtazapine Fails

If mirtazapine is ineffective or not tolerated, consider this sequence:

1. Trazodone 25-100 mg at bedtime: Moderate efficacy for improving sleep quality/duration, recommended for insomnia in multiple guidelines [1, @8@, 1]

2. Venlafaxine (SNRI): May be superior to SSRIs for treating anxiety in some studies, though evidence is mixed [@6@, 1]

3. Short-intermediate acting benzodiazepine receptor agonists (Z-drugs): Zolpidem 5 mg at bedtime could be considered for refractory insomnia, but only with extreme caution given substance use history 1

   • Z-drugs were developed to prevent over-sedation but still carry dependence risk [@3@]
   • Should be supplemented with behavioral and cognitive therapies 1

Critical Monitoring and Follow-Up

This patient requires close monitoring:

• Follow-up every few weeks initially to assess effectiveness, side effects, and need for ongoing medication [@1@]
• Monitor for suicidal thoughts or actions, as antidepressants carry this risk (approximately 1 in 500 patients) [@11@]
• Watch for signs of alcohol relapse, as less drinking is associated with improved depression outcomes [@16@]
• Assess for medication adherence and response to CBT-I interventions 1

Common Pitfalls to Avoid

• Do not restart benzodiazepines for long-term management despite previous Valium use—this perpetuates dependence risk [@2@, 1]
• Do not use gabapentinoids as "safer" alternatives—they carry similar dependence risks [@2@, 1, @11@]
• Do not rely on propranolol alone for this complex presentation [@9@]
• Do not prescribe sleep medications without concurrent CBT-I—pharmacotherapy should be supplemented with behavioral interventions 1
• Do not abruptly discontinue any medications if switching—taper carefully to avoid withdrawal symptoms [1, @3