Should Abilify (aripiprazole) be reinstated in a patient with a history of Major Depressive Disorder (MDD) and Generalized Anxiety Disorder (GAD) who has been off the medication for 2 months due to lack of refills, but reports doing fine while continuing Wellbutrin (bupropion) and Buspar (buspirone)?

Should Abilify Be Reinstated or Discontinued?

Do not reinstate Abilify (aripiprazole) in this patient who reports doing well for 2 months without it while continuing Wellbutrin and Buspar. The patient has essentially completed an unintentional but successful medication trial demonstrating that the combination of bupropion and buspirone alone is sufficient to maintain his psychiatric stability.

Clinical Reasoning

Evidence for Aripiprazole's Role in MDD

• Aripiprazole is FDA-approved as adjunctive therapy to antidepressants for major depressive disorder, not as monotherapy 1
• Its primary indication is for patients who have failed to achieve adequate response with antidepressant monotherapy 1
• The approval was based on 6-week trials showing benefit when added to ongoing antidepressants in treatment-resistant cases 1

Current Clinical Status Assessment

The patient's current presentation argues strongly against reinstatement:

• He reports "doing fine" after 2 months off aripiprazole, which represents an adequate trial period to assess stability 2
• His current regimen (bupropion + buspirone) is evidence-based: low-quality evidence shows no difference in response or remission between augmenting with bupropion versus buspirone, though bupropion may reduce depression severity slightly more 2
• The combination of bupropion and buspirone addresses both MDD and GAD without the metabolic and neurological risks of an atypical antipsychotic 3

Risk-Benefit Analysis Favors Discontinuation

Continuing aripiprazole unnecessarily exposes the patient to significant risks:

• Akathisia occurs at higher rates in MDD patients (though usually mild-to-moderate) compared to schizophrenia populations 1
• Weight gain, though minimal in short-term trials, can become clinically significant with longer-term use (≥100 weeks) 4
• Extrapyramidal symptoms occurred in up to 28% of patients in clinical trials 4
• An aripiprazole discontinuation syndrome has been described, though the patient has already been off for 2 months without apparent withdrawal symptoms 5

Maintenance Therapy Principles

Guidelines support continuing effective antidepressant therapy but do not mandate polypharmacy:

• A meta-analysis of 31 randomized trials supports continuation of antidepressant therapy to reduce relapse risk 2
• However, this applies to medications that are actively contributing to the patient's stability 2
• The patient's 2-month stability without aripiprazole demonstrates it is not necessary for maintaining remission

Clinical Algorithm for Decision-Making

Follow this approach:

1. Document current symptom status using standardized measures (PHQ-9 or HAM-D) to objectively confirm "doing fine" 2

2. If symptoms are truly in remission (PHQ-9 <5 or HAM-D ≤7):

   • Continue current regimen of bupropion and buspirone
   • Do not reinstate aripiprazole
   • Schedule follow-up in 4-6 weeks to monitor stability

3. If subtle residual symptoms emerge upon closer assessment:

   • Optimize doses of bupropion and/or buspirone before considering aripiprazole reinstatement
   • Consider adding cognitive behavioral therapy, which shows equivalent efficacy to medication augmentation 2

4. Only reinstate aripiprazole if:

   • Clear symptom recurrence occurs despite optimized bupropion/buspirone
   • Patient had documented superior response with the three-drug combination previously
   • Patient specifically requests reinstatement after informed discussion of risks/benefits

Critical Pitfalls to Avoid

• Do not reflexively reinstate medications simply because they were previously prescribed – the patient has provided real-world evidence that aripiprazole is unnecessary 2
• Do not confuse "stable on three medications" with "requires three medications" – parsimony in prescribing reduces adverse effects and improves adherence 1
• Do not ignore the patient's subjective report of doing well – patient-reported outcomes are valid measures of treatment success 2
• Beware of polypharmacy inertia – medications are often continued indefinitely without reassessment of ongoing necessity 2

The patient has inadvertently demonstrated successful simplification of his regimen. This should be viewed as a therapeutic success, not a medication error requiring correction 2.