What is the best course of action for a 23-year-old male with major depressive disorder (MDD), questionable attention deficit hyperactivity disorder (ADHD), and generalized anxiety disorder (GAD) who remains symptomatic after 3 weeks on Wellbutrin (bupropion) 150mg and Duloxetine (duloxetine) 90mg, and has been started on Alprazolam (alprazolam) 5mg?

Critical Error in Current Management

You have made a significant medication error: there is no such medication as "Alify 5mg" or alprazolam 5mg for this indication—you likely meant aripiprazole (Abilify) 5mg, but this is premature and not guideline-concordant at only 3 weeks of antidepressant treatment.

Immediate Action Required

Stop and reassess: 3 weeks is insufficient time to declare treatment failure with your current regimen of bupropion 150mg and duloxetine 90mg. 1

• Allow a minimum of 6-8 weeks at therapeutic doses before modifying treatment, as this is the evidence-based timeframe for adequate antidepressant trial 1, 2
• Your current bupropion dose of 150mg is subtherapeutic—therapeutic dosing for depression is 300-450mg daily 3, 4
• Duloxetine 90mg is within therapeutic range, but the combination hasn't had adequate time to work

Correct Treatment Algorithm

Step 1: Optimize Current Regimen (Do This Now)

Increase bupropion to 300mg daily (bupropion XL preferred for once-daily dosing) and continue duloxetine 90mg for a full 6-8 weeks before declaring treatment failure. 1, 2, 3

• This combination (duloxetine + bupropion) achieves remission rates of approximately 50% compared to 30% with monotherapy 2, 4
• The combination is well-studied and effective for treatment-resistant depression 3, 4
• Monitor for response every 2-4 weeks using standardized depression scales (PHQ-9) 2

Step 2: Address the Questionable ADHD

Do not treat ADHD until the MDD is adequately addressed, as MDD is the primary disorder causing severe symptoms (crying, feeling bad). 1

• When MDD is primary or accompanied by severe symptoms, it must be the focus of treatment first 1
• Bupropion has the added benefit of treating both depression and ADHD symptoms, making it ideal for this patient 5, 6
• After 6-8 weeks, if depressive symptoms remit but ADHD symptoms remain problematic, then consider adding a stimulant 1

Step 3: Manage the GAD Component

The current combination of duloxetine (SNRI) and bupropion addresses both depression and anxiety. 2

• Duloxetine is FDA-approved for GAD and provides dual serotonin-norepinephrine action 2
• If anxiety remains problematic after 8-12 weeks of optimized pharmacotherapy, add cognitive-behavioral therapy (CBT), which demonstrates superior efficacy when combined with medication 2
• Avoid benzodiazepines (if you meant alprazolam) for chronic GAD management in a 23-year-old with depression due to dependence risk and potential worsening of depression

Step 4: If Treatment Fails After 8 Weeks at Optimized Doses

Consider switching to venlafaxine XR (SNRI) 75-225mg daily, which demonstrates statistically significantly better response rates than SSRIs in treatment-resistant depression. 1, 2

• Switching between medication classes (rather than augmenting with antipsychotics) is preferred as second-step treatment 1
• Aripiprazole augmentation showed similar efficacy to bupropion augmentation in one trial, but had higher discontinuation rates and is not first-line 1

Critical Monitoring Requirements

• Assess for suicidal ideation at every visit, particularly during the first 1-2 months after medication changes, as suicide risk is greatest during this period 2
• Monitor for behavioral activation, agitation, or worsening anxiety, especially with bupropion dose increases 2
• Use standardized rating scales (PHQ-9 for depression, GAD-7 for anxiety) every 2-4 weeks to objectively track response 2

Common Pitfalls to Avoid

• Premature switching or augmentation before allowing adequate trial duration (6-8 weeks at therapeutic dose) leads to missed opportunities for response 2
• Starting antipsychotics (aripiprazole) as third-line agents before optimizing first-line antidepressant combinations 1
• Treating ADHD before stabilizing severe MDD, which can worsen anxiety and agitation 1
• Underdosing bupropion—150mg is a starting dose, not a therapeutic dose for depression 3, 4, 6

Duration of Continuation Therapy

• Continue treatment for 4-9 months after achieving remission for a first episode of MDD 2
• For recurrent depression (2+ episodes), consider years to lifelong maintenance therapy 2