How should the patient's current medication regimen be adjusted to better manage their depressive symptoms, given their partial response to Prozac (fluoxetine) and recent initiation of Bupropion (bupropion) augmentation?

Medication Adjustment Recommendation

Increase bupropion to XL 300 mg once daily as the patient has requested, which will address both the persistent depressive symptoms and adherence issues with the twice-daily dosing. 1

Rationale for This Adjustment

The patient demonstrates a partial response to the current regimen (fluoxetine 40 mg + bupropion 100 mg twice daily), with improvement in mood and reduction in self-harm ideation but persistent low energy and occasional hopelessness. 2 The American College of Physicians guidelines explicitly recommend modifying treatment when patients do not have adequate response within 6-8 weeks of therapy initiation. 2

Why Bupropion XL 300 mg is Appropriate

• Dosing optimization: The FDA-approved target dose for major depressive disorder is 300 mg once daily, which can be reached after 4 days at 150 mg. 1 Your patient is currently only receiving 200 mg total daily (100 mg twice daily), which is subtherapeutic.

• Adherence improvement: The patient reports forgetting evening doses, making once-daily XL formulation ideal. 1 Improved adherence directly correlates with better treatment outcomes. 2

• Augmentation evidence: Bupropion as an augmenting agent to SSRIs shows significant efficacy, with one study demonstrating 60% remission rates versus 24% with SSRI alone in partial responders. 3 The STAR*D trial found that 1 in 4 patients achieved remission when switching or augmenting after initial treatment failure. 2

Safety Considerations

Monitor for Serotonin Syndrome Risk

While rare, the combination of fluoxetine (SSRI) and bupropion carries a theoretical risk of serotonin syndrome. 4 Key warning signs to monitor:

• Myoclonic jerks or tremor
• Confusion or altered mental status
• Autonomic instability (fever, sweating, blood pressure changes)
• Neuromuscular hyperactivity

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This risk is primarily mediated by bupropion's inhibition of CYP2D6, which can increase fluoxetine levels. 1, 4 However, at therapeutic doses, this combination is commonly used and generally well-tolerated.

Seizure Risk Management

The patient's current dose is well below seizure-risk thresholds. 1 The maximum recommended dose is 450 mg daily for bupropion XL, and seizure risk increases primarily with:

• Doses exceeding 450 mg daily
• Rapid dose escalation
• History of seizures, eating disorders, or abrupt alcohol/benzodiazepine discontinuation (none reported here)

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Timeline and Follow-up

Reassess within 2 weeks of the dose increase, as recommended by ACP guidelines for monitoring therapeutic response and adverse effects. 2

• If inadequate response persists at 6-8 weeks on optimized doses, consider further augmentation strategies or switching antidepressants. 2

• For first-episode depression with satisfactory response, plan to continue treatment for 4-9 months after remission. 2 Given the patient's self-harm history, err toward the longer duration.

Addressing Residual Symptoms

The patient's persistent low energy may improve with optimized bupropion dosing, as bupropion's dopamine-norepinephrine reuptake inhibition specifically targets neurovegetative symptoms. 5 Unlike SSRIs, bupropion is less likely to cause sedation and may provide activating effects beneficial for energy levels. 5

The trazodone for sleep should be continued as insomnia management is appropriate and does not interfere with the antidepressant regimen. 2