What is a suitable addition to alleviate persistent anxiety symptoms in a patient taking buspirone 7.5 MG BID, duloxetine 20 MG BID, dextromethorphan-bupropion ER at bedtime, hydroxyzine as needed, and trazodone for sleep?

Adding a Medication for Persistent Anxiety with Multiple Current Medications

For a patient with persistent anxiety despite multiple medications, quetiapine is the most appropriate addition due to its sedating properties and lower risk of extrapyramidal side effects compared to other antipsychotics.

Current Medication Analysis

The patient is currently taking:

• Buspirone 7.5 mg BID (anxiolytic)
• Duloxetine 20 mg BID (SNRI antidepressant)
• Dextromethorphan-bupropion ER (Auvelity) at bedtime (NMDA antagonist/antidepressant)
• Hydroxyzine PRN (antihistamine for anxiety)
• Trazodone (for sleep)

Despite this regimen targeting multiple neurotransmitter systems, the patient continues to experience anxiety symptoms.

Recommended Addition

First-line recommendation:

• Quetiapine (Seroquel) starting at 25 mg at bedtime
  • Initial dose: 25 mg immediate release orally
  • Schedule: Once daily at bedtime (can increase to twice daily if needed)
  • Titration: May gradually increase by 25 mg increments every 3-7 days based on response and tolerability
  • Target dose: 25-100 mg daily for anxiety symptoms

Rationale for Quetiapine

1. Evidence-based choice: Second-generation antipsychotics like quetiapine have demonstrated efficacy for anxiety when other medications have failed 1.

2. Complementary mechanism: Quetiapine works through different receptors (serotonin, dopamine, histamine) than the current medications, potentially addressing anxiety pathways not currently targeted.

3. Sedating properties: Quetiapine is sedating, which can be beneficial for anxiety and sleep disturbances 1.

4. Safety profile: Compared to first-generation antipsychotics, quetiapine is less likely to cause extrapyramidal side effects 1.

5. Dosing convenience: Can be given once daily at bedtime, simplifying the regimen.

Alternative Options (if quetiapine is not tolerated)

1. Olanzapine: 2.5-5 mg at bedtime

   • Benefits: Sedating, may help with sleep and anxiety
   • Caution: Higher metabolic risk than quetiapine 1

2. Aripiprazole: 5 mg once daily

   • Benefits: Less sedating, fewer metabolic effects
   • Caution: May cause akathisia or activation 1

3. Pregabalin: Start at 50 mg twice daily

   • Benefits: Different mechanism (calcium channel modulation)
   • Limitation: Less evidence in combination with current regimen

Important Monitoring and Precautions

1. Start low, go slow: Begin with the lowest possible dose and titrate gradually to minimize side effects.

2. Monitor for side effects:

   • Sedation/drowsiness (particularly with quetiapine)
   • Orthostatic hypotension
   • Metabolic changes (weight gain, lipid and glucose abnormalities)
   • QTc prolongation (especially with multiple medications)

3. Drug interactions:

   • Monitor for potential interactions between quetiapine and duloxetine (both affect serotonin)
   • Avoid combining with other CNS depressants when possible

4. Reassess regularly:

   • Evaluate response after 2-4 weeks
   • Consider tapering/discontinuing medications that aren't providing benefit

Medication Optimization Before Adding

Before adding a new medication, consider:

• Optimizing buspirone dose (could increase to 10-15 mg BID if tolerated)
• Ensuring adequate duloxetine dosing (current dose is lower than typical anxiety treatment dose)
• Evaluating adherence to current medications
• Assessing if hydroxyzine is being used optimally

Non-pharmacological Considerations

While adding medication, also recommend:

• Cognitive-behavioral therapy for anxiety
• Mindfulness-based stress reduction techniques
• Regular exercise and sleep hygiene practices

The patient's complex medication regimen requires careful consideration of drug interactions and side effect profiles, making quetiapine a reasonable next step for persistent anxiety symptoms.