What adjustments can be made to the treatment regimen for a patient with increased depressive and anxiety symptoms while on Vyvanse (lisdexamfetamine) and Wellbutrin (bupropion) extended release?

Treatment Adjustment for Worsening Depression and Anxiety on Vyvanse and Wellbutrin

Increase Wellbutrin XL to 300mg daily and add PRN clonidine 0.1mg for anxiety as planned, while prioritizing treatment of depressive symptoms first, with close monitoring at 4 and 8 weeks to assess response and adjust if needed. 1

Rationale for Prioritizing Depression Treatment

• When patients present with comorbid depression and anxiety symptoms, treatment of depressive symptoms should be prioritized first. 1 This is a strong recommendation based on high-quality evidence from ASCO guidelines.

• Amanda's presentation includes depressive symptoms (feeling down and hopeless more than half the days, anhedonia for several days, sleep disturbance) alongside anxiety symptoms (feeling anxious and on edge more than half the days, excessive worrying). 1

• The current evidence supports that treating depression first often improves anxiety symptoms concurrently, and many patients (50-60%) with depression have comorbid anxiety disorders. 1

Wellbutrin Dose Escalation

The planned increase from 150mg to 300mg daily is appropriate and follows standard dosing guidelines:

• Bupropion (Wellbutrin) dosing should be increased using increments of the initial dose every 5-7 days until therapeutic benefits or significant side effects become apparent. 1

• The maximum recommended dose for bupropion extended-release is typically 300mg daily for depression, with doses given before 3 PM to minimize insomnia risk. 1

• Bupropion has demonstrated particular efficacy for anhedonia and low positive affect symptoms, which Amanda is experiencing ("little pleasure in doing things"). 2 This makes it an especially appropriate choice for her symptom profile.

• Bupropion's activating properties can improve energy and reduce apathy, which aligns with Amanda's report of good daytime energy but emerging depressive symptoms. 1, 2

Addressing Anxiety with Clonidine

The addition of PRN clonidine 0.1mg twice daily for anxiety is reasonable as an adjunctive strategy:

• While guidelines recommend treating depression first, adjunctive medications for anxiety symptoms can be used when anxiety is prominent and causing functional impairment. 1

• Clonidine provides PRN relief without the long-term dependence risks of benzodiazepines, which require longer tapering periods and can be problematic. 1

• However, monitor blood pressure carefully, as Amanda is on Vyvanse (lisdexamfetamine), and the combination requires attention to cardiovascular effects. 3

Critical Monitoring Requirements

Regular assessment is essential and non-negotiable:

• Assess treatment response at 4 weeks and 8 weeks using standardized measures (such as PHQ-9 for depression, GAD-7 for anxiety). 1 This allows for objective tracking of symptom improvement.

• At each assessment point, evaluate:

  • Extent of symptom relief 1
  • Side effects and adverse events (particularly blood pressure, sleep, appetite) 1, 3
  • Patient satisfaction with treatment 1
  • Adherence to the regimen 1

• If symptoms are stable or worsening after 8 weeks despite good adherence, adjust the regimen. 1 Options include adding a psychological intervention, changing medications, or augmenting with another agent. 1

Important Considerations Specific to Amanda's Case

Vyvanse and stimulant effects:

• Amanda reports increased hyperfocus on weekends and feeling like she is "masking" all the time. Monitor whether Vyvanse is contributing to anxiety symptoms, as stimulants can exacerbate anxiety. 3

• The FDA label for bupropion notes that blood pressure monitoring is recommended when combined with stimulant medications, though this specifically references nicotine replacement. 3 The principle of cardiovascular monitoring applies to Vyvanse as well.

Sleep hygiene:

• Amanda attributes sleep trouble to "external factors" and not following her nighttime routine. Address sleep hygiene as a priority, as poor sleep perpetuates both depression and anxiety. 1

• Bupropion's activating properties make timing crucial—ensure the 300mg dose is taken in the morning to avoid insomnia exacerbation. 1

Appetite concerns:

• Amanda's ongoing appetite struggles predate Vyvanse but warrant monitoring. Bupropion does not typically cause appetite suppression and may actually help with energy for meal preparation. 1

When to Consider Alternative Strategies

If inadequate response at 8 weeks:

• Consider adding evidence-based psychotherapy (CBT) if not already incorporated into her current therapy. 1 A unified protocol combining CBT for depression and anxiety may be particularly useful. 1

• If pharmacologic adjustment is needed, options include:

  • Switching to an SSRI/SNRI (though these carry sexual dysfunction and weight gain risks that bupropion avoids) 1, 4
  • Adding a second antidepressant (though evidence for specific combinations is limited) 1
  • Augmentation with an atypical antipsychotic for treatment-resistant anxiety (though this is typically reserved for more severe cases) 5

Common pitfall to avoid: Do not assume bupropion is ineffective for anxiety. While psychiatrists often avoid prescribing bupropion for patients with high anxiety, empirical evidence does not support differential response based on anxiety symptoms. 4 The activating properties are often misinterpreted as anxiety-worsening, but this is not consistently demonstrated in clinical trials. 6, 7, 4

Safety Monitoring

• Screen for bipolar disorder risk factors before continuing bupropion escalation, as antidepressants can precipitate manic episodes. 3 Amanda's history should be reviewed for family history of bipolar disorder.

• Monitor for neuropsychiatric symptoms (concentration disturbance, paranoia, confusion), which can occur with bupropion and may require dose reduction or discontinuation. 3

• Ensure Amanda knows to report any signs of allergic reactions, chest pain, or significant mood changes immediately. 3