What are the next steps in treatment for a patient on Wellbutrin (bupropion) ER 300mg daily for Major Depressive Disorder (MDD), Generalized Anxiety Disorder (GAD), and Attention Deficit Hyperactivity Disorder (ADHD)?

Treatment Optimization for a 42-Year-Old Female on Bupropion ER 300mg Daily

The next step is to assess treatment response after 4-12 weeks: if MDD/ADHD symptoms have adequately improved, continue current therapy and monitor; if symptoms persist despite adequate trial, add a stimulant medication (methylphenidate or lisdexamfetamine) for ADHD while continuing bupropion for MDD, or switch to an SSRI if GAD symptoms remain problematic. 1

Assessment of Current Treatment Response

Evaluate Each Condition Separately

Major Depressive Disorder (MDD):

• Bupropion 300mg daily is an appropriate and effective dose for MDD treatment 2
• The FDA-approved target dose for MDD is 300mg once daily, which this patient is already receiving 2
• If depressive symptoms have not adequately responded after 6-12 weeks at 300mg, consider switching to an alternative antidepressant rather than increasing bupropion dose 1

Generalized Anxiety Disorder (GAD):

• Critical caveat: Bupropion is NOT first-line for GAD and may actually worsen anxiety symptoms 2
• If GAD symptoms remain problematic or have worsened, adding an SSRI to the bupropion regimen is appropriate 1
• Evidence shows SSRIs combined with bupropion can effectively treat comorbid depression and anxiety 1

ADHD:

• Bupropion is only a second-line agent for ADHD at best 1
• Stimulants (methylphenidate or lisdexamfetamine) are first-line therapy and should be considered if ADHD symptoms persist 1

Algorithmic Approach to Next Steps

Step 1: Determine Primary Symptom Burden (4-12 weeks after initiation)

If MDD is primary or most severe:

• Continue bupropion 300mg daily if showing response 2
• If inadequate response, switch to alternative antidepressant (SSRI/SNRI) per STAR*D trial findings showing 25% remission rate with medication switches 1
• Venlafaxine XR, sertraline, or escitalopram are reasonable alternatives 1

If ADHD symptoms are primary or most impairing:

• Add a stimulant medication to bupropion rather than switching 1
• Methylphenidate 5-20mg three times daily or long-acting formulations are preferred first-line options 1
• Lisdexamfetamine is an alternative first-line stimulant option 1
• The rapid onset of stimulant action (days) allows quick assessment of ADHD symptom improvement 1

If GAD symptoms are primary or most impairing:

• Add an SSRI to bupropion (do not use bupropion monotherapy for GAD) 1
• Sertraline, paroxetine, or escitalopram are appropriate choices for comorbid depression and anxiety 1
• If anxiety does not respond to pharmacotherapy, consider adding cognitive behavioral therapy 1

Step 2: Combination Therapy Strategy

For persistent ADHD + MDD (both inadequately treated):

• Continue bupropion 300mg daily for MDD 2
• Add methylphenidate or lisdexamfetamine for ADHD 1
• This combination addresses both conditions with their respective first-line agents 1

For persistent GAD + MDD:

• Continue bupropion 300mg daily for MDD 2
• Add SSRI (sertraline, escitalopram, or paroxetine) for GAD 1
• Monitor for serotonin syndrome, though risk is low with this combination 2

For all three conditions inadequately controlled:

• Continue bupropion 300mg daily for MDD 2
• Add stimulant for ADHD 1
• Add SSRI for GAD 1
• This triple therapy approach is supported by guidelines for comorbid conditions 1

Critical Monitoring Parameters

Safety Considerations with Current Dose

Seizure risk monitoring:

• The 300mg daily dose is below the maximum 450mg daily limit that increases seizure risk 2
• Avoid in patients with seizure history, eating disorders, or abrupt alcohol/benzodiazepine discontinuation 2

Blood pressure monitoring:

• Bupropion can increase blood pressure; monitor at each visit 1
• Particularly important if adding stimulants, which also increase blood pressure 1

Neuropsychiatric monitoring:

• Monitor for suicidal ideation, especially in patients under 24 years (though this patient is 42) 2
• Watch for activation of mania/hypomania, psychosis, or behavioral changes 2

Common Pitfalls to Avoid

Do not use bupropion monotherapy for GAD - it lacks efficacy for anxiety and may worsen symptoms 1

Do not switch away from bupropion prematurely for ADHD - instead, add a stimulant as bupropion provides MDD coverage 1

Do not exceed 450mg daily of bupropion - seizure risk increases significantly above this dose 2

Do not combine with MAOIs - allow 14 days washout period between medications 2

Do not use in patients requiring opioid therapy - if using naltrexone-bupropion combination formulations 1

Reassessment Timeline

• Evaluate treatment response at 4-6 weeks for ADHD symptoms (stimulants have rapid onset) 1
• Evaluate treatment response at 6-12 weeks for MDD symptoms 1, 2
• Evaluate treatment response at 6-12 weeks for GAD symptoms if SSRI added 1
• Periodically reassess need for maintenance treatment and appropriate dosing 2