What are the best management options for an adult patient with a history of Attention Deficit Hyperactivity Disorder (ADHD) and Major Depressive Disorder (MDD), currently taking Wellbutrin (bupropion) 300mg and Adderall (amphetamine and dextroamphetamine) 30mg, who is experiencing fatigue throughout the day and is going through a stressful divorce?

Management of Fatigue in a Patient with ADHD and MDD on Bupropion and Adderall During Divorce

Primary Recommendation: Optimize Stimulant Dosing First

The current Adderall dose of 30 mg daily is likely suboptimal and should be increased to address persistent fatigue, as adults with ADHD typically require 40 mg daily for optimal symptom control, and the divorce-related stress may be unmasking undertreated ADHD symptoms that contribute to exhaustion. 1

• The American Academy of Child and Adolescent Psychiatry recommends titrating amphetamine salts upward by 5-10 mg weekly until symptoms resolve, with maximum daily doses for adults reaching 40 mg, though some patients may require up to 65 mg total daily dose with clear documentation that lower doses were insufficient 1
• Stimulants achieve 70-80% response rates when properly titrated, and systematic titration to optimal effect is more important than strict mg/kg calculations 1
• The current 30 mg dose falls below the typical maintenance range of 40 mg daily, suggesting room for optimization before considering additional interventions 1

Critical Assessment: Rule Out Medication-Related Fatigue

• Bupropion at 300 mg daily is at the standard maintenance dose and is inherently activating rather than sedating, making it an unlikely contributor to fatigue 1, 2
• Do not add atomoxetine or switch to it, as somnolence and fatigue are its most common adverse effects, which would directly worsen the patient's primary complaint 1
• The combination of bupropion and stimulants has no significant pharmacokinetic interactions and is well-established as safe, with careful monitoring for side effects necessary 1

Addressing the Psychosocial Context

• The divorce represents a significant life stressor that can manifest as fatigue independent of medication optimization 1
• Cognitive Behavioral Therapy (CBT) specifically developed for ADHD has been found most effective when combined with medication and helps with emotion regulation, executive function, and quality of life 1
• Mindfulness-Based Cognitive Therapy (MBCT) helps most profoundly with inattention symptoms, emotion regulation, and executive function, which may be particularly relevant during high-stress periods 1

Specific Titration Protocol

• Increase Adderall to 35 mg daily (add 5 mg to morning dose) and monitor for one week 1
• If fatigue persists without prohibitive side effects, increase to 40 mg daily (20 mg twice daily or 40 mg extended-release once daily) 1
• Obtain weekly symptom ratings during dose adjustment, specifically asking about energy levels, task completion, and any side effects like insomnia or appetite suppression 1

Monitoring Parameters During Optimization

• Monitor blood pressure and pulse at each visit, as stimulants can affect cardiovascular parameters 1
• Track sleep quality and timing, as inadequate or disrupted sleep from evening stimulant effects can paradoxically worsen daytime fatigue 1
• Monitor appetite and weight, as appetite suppression is common with stimulants 1
• Screen for worsening depressive symptoms or suicidal ideation, particularly given the divorce stressor 1

Alternative Considerations if Stimulant Optimization Fails

• If fatigue persists despite optimal stimulant dosing (40 mg daily), consider adding an SSRI if depressive symptoms have emerged or worsened during the divorce, as the American Academy of Child and Adolescent Psychiatry recommends adding an SSRI to the stimulant regimen when mood symptoms persist despite ADHD improvement 1
• The current bupropion dose of 300 mg daily is already at the standard target for depression, so increasing it further (maximum 450 mg daily) is an option but carries increased seizure risk 2, 3
• Never combine MAO inhibitors with stimulants or bupropion due to severe hypertension risk and potential cerebrovascular accidents 1, 2

Common Pitfalls to Avoid

• Do not assume the current 30 mg Adderall dose is adequate, as 54-70% of adults with ADHD respond optimally when proper titration protocols are followed 1
• Do not attribute all fatigue to depression without optimizing ADHD treatment first, as individuals with ADHD who stopped their psychostimulant medication had a significant increase in depressive symptoms despite remaining on their antidepressant 1
• Do not add sedating medications like hydroxyzine or other PRN anxiolytics, as these will worsen daytime fatigue 1
• Do not switch from bupropion to another antidepressant, as the STAR*D trial showed no difference in response or remission rates between various antidepressant switches, and bupropion addresses both ADHD and depression simultaneously 4, 1