Should aripiprazole (Abilify) be restarted as augmentation for an adult with major depressive disorder and generalized anxiety disorder who is on bupropion (Welurin) 150 mg daily and buspirone 15 mg twice daily after stopping aripiprazole and now feels depressed?

Should Aripiprazole Be Restarted for This Patient?

Yes, reinstate aripiprazole as augmentation to bupropion 150mg daily, as aripiprazole augmentation demonstrates superior remission rates (28.9% vs 22.3%) compared to antidepressant monotherapy in treatment-resistant depression, and this patient has already shown prior tolerability to the medication. 1

Rationale for Aripiprazole Augmentation

The current regimen is suboptimal for several reasons:

• Bupropion 150mg daily is below the therapeutic target for major depressive disorder, which typically requires 300-400mg daily for adequate antidepressant effect 2, 3
• Buspirone 15mg twice daily addresses anxiety but has limited antidepressant efficacy, with significantly higher discontinuation rates (20.6%) compared to other augmentation strategies 4, 3
• The patient previously tolerated aripiprazole, making reinstatement a logical choice given established safety in this individual 1

Evidence Supporting Aripiprazole Augmentation

Aripiprazole is the only FDA-approved augmentation agent for treatment-resistant depression and demonstrates:

• Superior remission rates: 28.9% with aripiprazole augmentation versus 22.3% with switching antidepressants (RR 1.30,95% CI 1.05-1.60, P=0.02) 1
• Higher response rates: 74.3% versus 62.4% with switching strategies 1
• Significantly better remission at 6 weeks: 55.4% with aripiprazole versus 34.0% with bupropion augmentation (P=0.031) in direct comparison trials 5
• Rapid symptom improvement within days to weeks when added to existing antidepressants 6

Recommended Treatment Algorithm

Step 1: Optimize the current regimen before adding aripiprazole

• Increase bupropion from 150mg to 300mg daily (given as 150mg twice daily, with second dose before 3 PM to minimize insomnia) 2, 7
• Continue buspirone 15mg twice daily for anxiety management 4
• Allow 2-3 weeks at the optimized bupropion dose to assess response 3

Step 2: Add aripiprazole if depression persists

• Start aripiprazole 2.5-5mg daily, titrating to 10-15mg daily based on response and tolerability 6, 5
• Monitor for response within 1-2 weeks, as aripiprazole typically shows rapid effects 6
• Assess remission at 6 weeks using standardized depression scales 5

Step 3: Monitor for adverse effects

• Common side effects: somnolence, akathisia, weight gain (more frequent with aripiprazole than bupropion) 1
• Anxiety: Less common with aripiprazole (16.6%) compared to bupropion (24.3%) 1
• Akathisia: Responds to dose reduction if it occurs 6
• Metabolic monitoring: Weight and metabolic parameters should be tracked 6

Why Not Alternative Strategies?

Switching to another antidepressant is inferior to augmentation in this case:

• Moderate-quality evidence shows no significant difference when switching between antidepressants 3
• The patient has partial benefit from bupropion (addressing some symptoms), which would be lost with switching 3
• Augmentation with aripiprazole outperforms switching strategies (28.9% vs 22.3% remission) 1

Buspirone augmentation alone is inadequate:

• Buspirone has similar efficacy to bupropion augmentation but significantly higher discontinuation rates due to adverse events (20.6% vs 12.5%, P<0.001) 3
• The patient is already on buspirone without adequate response 4

Critical Monitoring Requirements

• Assess suicidal ideation during the first 1-2 months after any medication change, as suicide risk is greatest during this period 3
• Monitor for akathisia and restlessness within the first week of aripiprazole initiation 1, 6
• Track weight and metabolic parameters at baseline and monthly 1
• Evaluate treatment response at 2,4, and 6 weeks using standardized depression scales 5

Duration of Treatment

• Continue combination therapy for 4-9 months after achieving satisfactory response for first-episode MDD 3
• Consider longer-term maintenance (years to lifelong) given the patient's history of both MDD and GAD, which suggests recurrent illness 3

Common Pitfalls to Avoid

• Do not add aripiprazole before optimizing bupropion dose to 300mg daily, as the current 150mg dose is subtherapeutic 2, 3
• Do not expect immediate results from buspirone - it requires 2-4 weeks for full effect and is primarily anxiolytic, not antidepressant 4
• Do not discontinue medications abruptly - bupropion and buspirone both require gradual tapering if changes are needed 4
• Do not ignore early akathisia - it responds well to dose reduction and should not lead to premature discontinuation 6