After 10 days of Wellbutrin (bupropion) 150 mg daily and Abilify (aripiprazole) 7.5 mg daily, I am experiencing increased anhedonia and boredom; is this a side effect and how should I manage it?

Increased Anhedonia and Boredom After 10 Days of Wellbutrin and Abilify

After only 10 days of treatment, you have not yet reached the 6–8 week window required to assess therapeutic response, and early worsening of motivational symptoms can occur during the initial treatment phase before improvement emerges. 1

Understanding the Timeline

• Full antidepressant effects typically emerge 6–8 weeks after achieving therapeutic dosing, not within the first 10 days. 1
• Early monitoring (weeks 1–2) is critical for detecting worsening depression, agitation, or behavioral changes, particularly in patients under 24 years of age. 1, 2
• The first 1–2 months carry the highest risk for suicide attempts and symptom fluctuations. 1, 2

Possible Explanations for Your Symptoms

Insufficient Time for Therapeutic Effect

• Bupropion may produce more rapid improvement in energy levels within the first few weeks, but comprehensive antidepressant effects—including reduction of anhedonia—require 6–8 weeks at therapeutic doses. 1
• Your current dose of 150 mg daily is a starting dose; the standard therapeutic target is 300 mg/day (150 mg twice daily for SR formulation). 1

Early Activation Without Full Benefit

• Bupropion has activating properties that can initially cause agitation, restlessness, or akathisia before mood improvement occurs. 2, 3
• The FDA label warns that anxiety, agitation, irritability, and akathisia are reported early in treatment and may represent precursors to emerging symptoms rather than treatment failure. 2

Aripiprazole Contribution

• Aripiprazole at 7.5 mg can cause akathisia (23.6% incidence) and fatigue (23.6%), which may be misinterpreted as worsening anhedonia or boredom. 3
• In a 52-week study, akathisia was among the most common adverse events with adjunctive aripiprazole, often appearing early in treatment. 3

Immediate Management Steps

Do Not Discontinue Prematurely

• Do not stop treatment before 6–8 weeks unless significant adverse effects occur, as premature discontinuation prevents assessment of true efficacy. 1
• Response rates to antidepressant therapy may be as low as 50%, with 38% of patients not achieving response during 6–12 weeks—but this cannot be determined at day 10. 1

Monitor for Serious Warning Signs

• Contact your prescriber immediately if you experience: severe agitation, depressed mood worsening, suicidal thoughts, unusual behavioral changes, or symptoms that feel "not typical" for you. 2
• These symptoms require urgent evaluation to determine whether treatment should continue under closer monitoring or be discontinued. 2

Consider Dose Optimization

• Your bupropion dose of 150 mg once daily is subtherapeutic for most patients; the standard target is 300 mg/day (150 mg twice daily). 1
• Gradual titration to 150 mg twice daily after day 3–7 is recommended, provided you tolerate the initial dose. 1
• The second dose should be given before 3 PM to minimize insomnia risk. 1

Evaluate Aripiprazole Tolerability

• If akathisia or restlessness is prominent, lowering the aripiprazole dose (e.g., from 7.5 mg to 2.5–5 mg) can resolve these symptoms while maintaining antidepressant augmentation. 4
• One case series showed that akathisia responded to dose reduction without loss of efficacy. 4

Expected Trajectory

• Bupropion's activating effects may improve energy before mood, sometimes within the first few weeks, but anhedonia and motivational deficits typically require the full 6–8 weeks. 1
• Adjunctive aripiprazole has been shown to produce rapid improvement in depressive symptoms (within weeks), but sustained effects require longer observation. 4, 5
• In one study, 70% of aripiprazole patients had lower depression scores at the first follow-up visit, with 17% achieving remission early—but 50% remission rates were only seen at the end of the observation period. 5

Critical Safety Considerations

• The maximum bupropion dose is 450 mg/day to maintain seizure risk at 0.1%; do not exceed 300 mg/day without clear clinical justification. 1, 2
• Seizure risk is approximately 0.1% (1 in 1,000) at 300 mg/day and increases nearly tenfold at doses above 450 mg/day. 2
• Blood pressure and heart rate should be monitored periodically, especially during the first 12 weeks, as bupropion can cause elevations. 1, 6

When to Reassess

• Schedule a follow-up within 1–2 weeks to monitor symptom progression, tolerability, and safety. 1
• If no adequate response occurs by 6–8 weeks at therapeutic doses (300 mg/day bupropion), consider dose adjustment, switching agents, or alternative augmentation strategies. 1
• Do not modify treatment based on 10-day outcomes, as this is insufficient time to assess efficacy. 1

Common Pitfall to Avoid

The most critical error is discontinuing effective treatment prematurely because early activation or lack of immediate benefit is mistaken for treatment failure, when in fact therapeutic effects have not yet had time to emerge. 1, 2