What dose of bupropion is effective for a 55-year-old female patient with depression and anxiety, already taking Prozac (fluoxetine) and escitalopram?

Bupropion Dosing for Treatment-Resistant Depression with Comorbid Anxiety

Critical Safety Concern First

This patient is already taking both Prozac (fluoxetine) and escitalopram—two SSRIs simultaneously—which is highly unusual and potentially dangerous. Before adding bupropion, you must address this polypharmacy issue, as combining multiple serotonergic agents increases the risk of serotonin syndrome 1.

Recommended Bupropion Dosing Strategy

For augmentation of inadequate SSRI response in depression with anxiety, initiate bupropion sustained-release (SR) at 150 mg once daily in the morning, then increase to 150 mg twice daily (300 mg/day total) after one week, which represents the effective therapeutic dose used in major clinical trials. 2

Dosing Algorithm

• Initial dose: Bupropion SR 150 mg every morning 2
• Titration: Increase by 150 mg every 3-7 days as tolerated 2
• Target therapeutic dose: 300 mg/day (150 mg twice daily) 2
• Maximum dose: 400 mg/day if needed, though 300 mg/day was the mean effective dose in STAR*D trials 2, 3
• Timing: Give second dose before 3 PM to minimize insomnia risk 2

Evidence Supporting This Approach

Augmentation vs. Switching

The landmark STAR*D trial demonstrated that augmenting an existing SSRI (citalopram) with bupropion SR showed similar efficacy to switching strategies, with significantly fewer discontinuations due to adverse events compared to buspirone augmentation (12.5% vs. 20.6%, P < 0.001). 2

• Augmentation with bupropion SR produced comparable remission rates to switching to other antidepressants 2
• No significant differences existed between various second-step treatment strategies in terms of response or remission 2
• Bupropion augmentation was better tolerated than buspirone augmentation 2

Efficacy in Depression with Anxiety

Bupropion demonstrates equivalent efficacy to SSRIs in treating depression with comorbid anxiety symptoms, contrary to older concerns about its use in anxious patients. 2

• Head-to-head trials showed no difference in efficacy between sertraline and bupropion for patients with MDD and anxiety 2
• The combination of escitalopram and bupropion-SR achieved 50% remission rates and 62% response rates in patients with chronic/recurrent MDD 3
• Mean effective doses in combination therapy studies were escitalopram 18 mg/day plus bupropion-SR 327-329 mg/day 3

Critical Clinical Considerations

Drug Interaction Warning

Bupropion inhibits CYP2D6, which can increase blood levels of both fluoxetine and escitalopram, potentially precipitating serotonin syndrome. 1

• Monitor closely for serotonergic symptoms: myoclonus, confusion, agitation, autonomic instability 1
• Consider reducing SSRI doses when adding bupropion 1
• The combination of bupropion with SSRIs requires careful monitoring but can be effective when properly managed 3

Contraindications and Precautions

Do not use bupropion in patients with seizure disorders or eating disorders; the seizure risk is dose-dependent. 2

• Avoid exceeding 150 mg per single dose 2
• Maximum daily dose should not exceed 400 mg 2, 3
• Use with caution in agitated patients, though evidence shows efficacy in anxious depression 2

Formulation Considerations

Bupropion SR (twice daily) and XL (once daily) formulations are bioequivalent under steady-state conditions, but SR allows more flexible dosing adjustments. 4, 5

• Bupropion XL can be dosed once daily at 150-300 mg 4
• SR formulation allows split dosing to minimize side effects 2, 3
• All formulations show equivalent systemic exposure to bupropion 4, 5

Expected Timeline and Monitoring

Full therapeutic response requires 4-8 weeks of treatment at target dose. 2

• Initial energy improvement may occur rapidly with bupropion's activating properties 2
• Reassess need for medication after 9 months of remission 2
• Discontinue gradually over 10-14 days to limit withdrawal symptoms 2

Advantages of Bupropion in This Context

Bupropion offers distinct advantages over increasing SSRI doses or adding additional serotonergic agents: minimal sexual dysfunction, no weight gain, and activating properties that may benefit low-energy depression. 2, 5

• Less somnolence compared to SSRIs and TCAs 5
• Significantly less sexual dysfunction than SSRIs 5
• May improve psychomotor retardation and cognitive symptoms 6
• No anticholinergic or significant cardiovascular effects at therapeutic doses 6