What is the best course of action for an adult patient with a history of depression, currently taking citalopram (escitalopram) and Wellbutrin (bupropion), who has been recently diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) and started on Vyvanse (lisdexamfetamine), and is now experiencing increased depressive symptoms?

Immediate Management of Worsening Depression After Starting Vyvanse

Stop the Vyvanse immediately and reassess the depression treatment regimen, as stimulants can unmask or worsen underlying mood symptoms, and this patient's antidepressant regimen may need optimization before reintroducing ADHD treatment. 1

Understanding What Likely Happened

• Stimulants do not treat depression and can paradoxically worsen depressive symptoms in some patients, particularly when the underlying mood disorder is inadequately controlled 1, 2
• The patient's current antidepressant combination (citalopram + bupropion) may have been providing insufficient coverage for their depression, which became apparent when the stimulant was added 1
• This represents a critical clinical pitfall: starting ADHD treatment before ensuring the depression is adequately controlled 1, 3

Immediate Action Steps

Step 1: Discontinue Vyvanse Temporarily

• Immediately stop the lisdexamfetamine to prevent further worsening of depressive symptoms 1
• Assess for suicidality using standardized tools like the PHQ-9, as this is a critical safety concern during any depression treatment change 4

Step 2: Optimize Depression Treatment First

• The depression must be adequately treated before addressing ADHD symptoms 1, 3
• Consider augmenting the current citalopram with additional bupropion if not already at therapeutic doses, as moderate-quality evidence shows augmenting citalopram with bupropion has lower discontinuation rates due to adverse events compared to other augmentation strategies 4
• Alternative approach: Switch from citalopram to a different SSRI (sertraline or venlafaxine), though moderate-quality evidence shows no difference in response when switching between SGAs 4
• Add cognitive behavioral therapy (CBT) to the medication regimen, as the American College of Physicians recommends either CBT or second-generation antidepressants as initial treatment, with combination therapy showing superior outcomes 4

Step 3: Monitor Depression Response

• Wait 6-12 weeks (the acute treatment phase) to assess response to the optimized depression regimen 4
• Use quantifiable tools like the PHQ-9 or HAM-D to measure improvement, defining response as ≥50% reduction in measured severity 4
• Do not restart ADHD treatment until depressive symptoms show clear improvement 1, 3

When and How to Restart ADHD Treatment

Timing of ADHD Medication Reintroduction

• Only restart ADHD treatment after achieving at least a 50% reduction in depression severity scores 4, 1
• The American Academy of Child and Adolescent Psychiatry recommends treating severe depression first before addressing ADHD symptoms 1

Preferred ADHD Treatment Strategy After Depression Stabilizes

• Restart with a stimulant (methylphenidate or amphetamine-based), NOT bupropion alone, as stimulants have 70-80% response rates for ADHD while bupropion is explicitly a second-line agent 1, 5
• Consider methylphenidate instead of returning to lisdexamfetamine, as approximately 40% of patients respond to only one stimulant class 1
• Start at low doses and titrate slowly while monitoring mood symptoms closely 1, 2

Safe Combination Therapy

• Once depression is stable, stimulants can be safely combined with SSRIs, as there are no significant drug-drug interactions between stimulants and SSRIs 1, 2
• A case series of 11 patients showed that fluoxetine or sertraline combined with psychostimulants was well-tolerated and effective for both ADHD and depression, with no patient developing suicidality, increased aggressiveness, or mania 2
• If ADHD symptoms improve but depressive symptoms persist after restarting stimulants, add an SSRI to the stimulant regimen rather than relying on bupropion alone 1

Critical Safety Warnings

• Never use MAO inhibitors concurrently with stimulants or bupropion due to risk of hypertensive crisis; at least 14 days must elapse between discontinuation of an MAOI and initiation of these medications 1
• Monitor systematically for suicidal ideation during any antidepressant adjustment, especially if treatment is associated with akathisia 1
• Avoid assuming bupropion alone will adequately treat both ADHD and depression, as no single antidepressant is proven for this dual purpose 1

Common Pitfalls to Avoid

• Do not continue the Vyvanse hoping the depression will improve – this directly contradicts the treatment algorithm for comorbid conditions 1, 3
• Do not assume the current antidepressant doses are adequate without formal assessment using validated scales 4
• Do not restart ADHD treatment prematurely before depression stabilizes, as this will likely result in the same outcome 1, 3
• Do not rely solely on bupropion for ADHD treatment when stimulants remain available, as bupropion has smaller effect sizes and is positioned as second-line 1, 5