What is the best course of action for a patient taking Wellbutrin (bupropion) 150mg and hydroxyzine 25mg up to 4 times daily who remains severely depressed?

Management of Severe Depression in a Patient on Bupropion and Hydroxyzine

The patient requires an increase in bupropion dosage to 300mg daily and would benefit from adding cognitive behavioral therapy (CBT) to their treatment regimen. 1

Current Situation Assessment

The patient is currently taking:

• Bupropion 150mg daily (subtherapeutic dose)
• Hydroxyzine 25mg up to 4 times daily (primarily an anxiolytic)

The patient is experiencing:

• Severe depression symptoms
• Lack of motivation to get out of bed
• Poor self-care (not brushing teeth or showering)

Recommended Treatment Algorithm

Step 1: Optimize Bupropion Dosage

• Increase bupropion to 300mg once daily (the usual target dose for MDD) 1, 2
• Monitor for improvement over the next 4-6 weeks
• Rationale: The current dose of 150mg is only the starting dose; the therapeutic dose is typically 300mg daily 2

Step 2: Add Evidence-Based Psychotherapy

• Initiate Cognitive Behavioral Therapy (CBT)
• Moderate-quality evidence shows CBT is as effective as second-generation antidepressants with fewer adverse effects 1
• Schedule weekly sessions for at least 8-12 weeks

Step 3: If No Improvement After 4-6 Weeks

• Consider switching from bupropion to another antidepressant with a different mechanism of action
• Alternatively, consider augmentation strategies:
  • Adding an SSRI (avoiding fluoxetine/paroxetine due to higher side effect profiles) 3
  • Consider mirtazapine as it has less fatigue-related side effects 3

Step 4: For Treatment-Resistant Depression

• If the patient fails to respond to two adequate trials of antidepressants from different classes (each lasting at least 4 weeks at therapeutic doses), they meet criteria for treatment-resistant depression 1
• Consider referral for brain stimulation therapies such as transcranial direct current stimulation (tDCS), which has shown efficacy in mild to moderate depression 4

Rationale for Recommendations

1. Bupropion Dosage Increase: The FDA-approved therapeutic dose for bupropion in major depressive disorder is 300mg daily 2. The current 150mg dose is only the recommended starting dose, which should be increased after 4 days to reach the target dose 2.

2. Addition of CBT: Strong evidence supports that CBT is as effective as antidepressant medication for depression. The American College of Physicians strongly recommends either CBT or second-generation antidepressants for treating major depressive disorder 1. CBT has shown lower relapse rates compared to medication alone.

3. Hydroxyzine Consideration: While hydroxyzine can help with anxiety symptoms, it is not a primary antidepressant. Research suggests that anxiolytics like hydroxyzine do not interfere with serotonergic antidepressants the way benzodiazepines might 5, so it can be continued for anxiety management.

Important Monitoring Considerations

• Monitor for seizure risk with increased bupropion dose (risk is dose-related) 2
• Watch for neuropsychiatric adverse events, including worsening depression, agitation, or suicidal thoughts 2
• Assess for improvement in depressive symptoms using standardized tools (e.g., PHQ-9) at each follow-up
• Schedule follow-up within 1-2 weeks of dose change to assess for side effects and initial response

Common Pitfalls to Avoid

1. Inadequate dosing: Many patients remain on the starting dose of bupropion (150mg) without reaching the therapeutic dose (300mg), leading to treatment failure 2

2. Overlooking psychotherapy: Relying solely on medication adjustments without adding evidence-based psychotherapy like CBT 1

3. Poor adherence monitoring: Weight gain and sexual dysfunction are common reasons for antidepressant non-adherence 6, but bupropion has a lower risk of these side effects compared to many other antidepressants

4. Premature switching: Not allowing adequate time (4-6 weeks) at therapeutic doses before determining treatment failure 3