What is the best course of action for a patient with Attention Deficit Hyperactivity Disorder (ADHD) and depression, who has been taking Wellbutrin (bupropion) for approximately one month without significant improvement in depressive symptoms, and is also experiencing urinary symptoms, including a weak urinary stream and interrupted stream, while using L-citrulline supplement, and has a history of anxiety, substance use, and current nicotine use via vaping?

Immediate Management of Urinary Symptoms and Depression Treatment Optimization

Discontinue L-Citrulline and Evaluate Urinary Symptoms

The urinary symptoms (weak/interrupted stream, frequent voiding) are most likely caused by the stimulant medication (presumably for ADHD), not bupropion, and the L-citrulline supplement should be discontinued immediately as it is not addressing the underlying cause. 1

• Stimulant medications commonly cause urinary hesitancy and retention through alpha-adrenergic effects on the bladder neck and urethral sphincter 1
• The temporal relationship (symptoms starting after stimulant initiation, improving with L-citrulline during peak stimulant effect, returning in evening as stimulant wears off) strongly suggests stimulant-induced urinary dysfunction 1
• L-citrulline as a vasodilator does not address alpha-adrenergic urinary effects and represents inappropriate self-treatment 1

Obtain a formal urological evaluation to rule out anatomical causes (prostate issues, urethral stricture) before attributing symptoms solely to medication. 1

Optimize Bupropion Dosing for Depression

Increase bupropion to 300 mg daily (if currently on 150 mg) and continue for a full 6-8 weeks at therapeutic dose before determining treatment response. 1, 2

• The patient reports taking bupropion for "approximately one month" but the current dose is not specified 1
• Therapeutic dosing for major depressive disorder requires 150 mg twice daily (300 mg total) for bupropion SR or 300 mg once daily for bupropion XL 1
• Allow 6-8 weeks at an adequate dose (300 mg daily) before determining treatment response, as antidepressants require this duration to achieve full therapeutic effect 1, 2
• The patient's report of "not noticing much difference" after one month may reflect inadequate dosing or insufficient treatment duration 1, 2

Address Persistent Anhedonia

The pervasive, lifelong anhedonia described by the patient may represent a core feature of persistent depressive disorder (dysthymia) or ADHD-related reward dysfunction rather than acute major depression, requiring augmentation strategies if bupropion monotherapy at 300 mg daily for 6-8 weeks proves insufficient. 2, 3

If Anhedonia Persists After 6-8 Weeks at Bupropion 300 mg Daily:

Add an SSRI (sertraline 50-200 mg daily or fluoxetine 20-40 mg daily) to bupropion rather than switching medications. 2, 1

• Augmenting SSRIs with bupropion decreases depression severity more effectively than buspirone augmentation (12.5% vs. 20.6% discontinuation due to adverse events, P < 0.001) 2
• The combination addresses depression through complementary mechanisms: SSRIs affect serotonin while bupropion works via noradrenergic/dopaminergic pathways 1
• Augmentation is equally effective as switching to another antidepressant but avoids discontinuation symptoms 2
• The patient has previously tolerated bupropion with Prozac (fluoxetine), making this combination a logical choice 1

Manage Urinary Symptoms Related to Stimulant Medication

Reduce the stimulant dose or switch to a non-stimulant ADHD medication (atomoxetine 60-100 mg daily or extended-release guanfacine 1-4 mg daily) if urological evaluation confirms medication-induced urinary dysfunction. 4

Specific Approach:

1. If on immediate-release stimulant: Switch to extended-release formulation to reduce peak-related side effects 4
2. If urinary symptoms persist: Reduce stimulant dose by 25-50% and reassess 4
3. If symptoms remain intolerable: Switch to atomoxetine (target dose 60-100 mg daily, requires 6-12 weeks for full effect) 4
   • Atomoxetine has fewer urinary side effects compared to stimulants 4
   • Particularly appropriate given comorbid depression and anxiety 4

Critical Monitoring Parameters

Monitor the following at each visit:

• Suicidality screening: Bupropion carries an FDA black box warning for increased suicidal thoughts in patients under 24 years with depression, requiring close monitoring especially during the first few months 5, 1
• Blood pressure and heart rate: Bupropion can elevate both parameters, particularly in the first 12 weeks 1
• Urinary symptoms: Track stream strength, frequency, and post-void residual sensation 1
• Depression severity: Use standardized scales (PHQ-9 or HAMD) to objectively track response 3
• ADHD symptom control: Ensure ADHD remains adequately treated if stimulant dose is reduced 4

Address Nicotine Vaping

The patient's nicotine vaping may be contributing to anxiety (rated 5/10) and should be addressed, particularly since bupropion is FDA-approved for smoking cessation at 150 mg twice daily (300 mg total). 1

• Begin nicotine cessation planning now rather than waiting until "after completing school" 1
• Current bupropion dosing (if optimized to 300 mg daily) is appropriate for dual treatment of depression and nicotine dependence 1
• Combining bupropion with nicotine replacement therapy (patches starting on quit date) achieves 35.5% abstinence at 12 months versus 30.3% with bupropion alone 1

Common Pitfalls to Avoid

• Do not assume bupropion has failed after only one month, especially if dose is subtherapeutic (< 300 mg daily) 1, 2
• Do not continue L-citrulline supplementation as it does not address the underlying mechanism of stimulant-induced urinary dysfunction 1
• Do not switch antidepressants prematurely—augmentation with an SSRI is preferred over switching 2
• Do not ignore the urinary symptoms as they significantly impact quality of life and may lead to medication non-adherence 1
• Do not overlook the need for formal urological evaluation to rule out anatomical causes 1