For an older adult on escitalopram 20 mg with partial response and significant anxiety, who is allergic to fluoxetine and paroxetine, can bupropion be used as an augmenting agent?

Bupropion Remains Recommended Despite Comorbid Anxiety

Bupropion can be safely used as an augmenting agent to escitalopram 20 mg in older adults with significant anxiety, as high-quality evidence from the STAR*D trial demonstrates that baseline anxiety does not diminish bupropion's comparative efficacy or tolerability. 1

Evidence Supporting Bupropion Use in Anxious Depression

Efficacy Is Not Reduced by Anxiety

• The American College of Physicians meta-analysis of STAR*D found that comorbid anxiety does not modify bupropion's antidepressant efficacy compared with other second-generation antidepressants 1
• Subgroup analyses confirmed no interaction between anxiety status and treatment response, meaning bupropion works equally well whether anxiety is present or absent 1
• In the STAR*D augmentation trial, bupropion achieved remission rates of 30.3% when added to citalopram (a close analog of escitalopram), comparable to buspirone augmentation 2

Safety Profile in Anxiety

• Large pooled analyses (n ≈ 12,800) showed anxiety occurred in only 0.6–5.4% of bupropion-treated patients versus 0.2–4.3% with placebo—no statistically significant difference 1
• Bupropion augmentation had significantly lower discontinuation rates due to adverse events (12.5%) compared with buspirone (20.6%, P < 0.001), indicating superior tolerability even in anxious patients 1, 2

Practical Implementation for This Patient

Dosing Strategy for Older Adults

• Start bupropion SR at 37.5 mg every morning, then increase by 37.5 mg every 3 days as tolerated 1
• Target dose is 150 mg twice daily (maximum 300 mg/day for older adults) 1
• Administer the second dose before 3 PM to minimize insomnia risk 1

Critical Pre-Treatment Screening

• Confirm no history of seizure disorders, eating disorders, or conditions predisposing to seizures (absolute contraindications) 1
• Verify blood pressure is controlled (<140/90 mm Hg), as bupropion can cause modest elevations 1
• Ensure patient is not on MAOIs or has discontinued them for at least 14 days 1
• Confirm no allergy to bupropion itself (patient has fluoxetine/paroxetine allergies but these do not cross-react) 3

Monitoring Protocol

• Assess for suicidal ideation, agitation, or behavioral changes during the first 1–2 weeks, as this period carries highest risk 1
• Monitor blood pressure and heart rate periodically, especially in the first 12 weeks 1
• Evaluate treatment response at 6–8 weeks after reaching therapeutic dose before declaring failure 1

Advantages Over Alternative Strategies

Why Bupropion Over Buspirone

• Both achieve similar remission rates (≈30%), but bupropion produces greater reduction in symptom severity (25.3% vs. 17.1% decrease in depression scores, P < 0.04) 2
• Bupropion has significantly better tolerability with lower dropout rates 2
• Bupropion addresses low energy and motivation, which often persist with SSRI monotherapy 1

Why Augmentation Over Switching

• The patient has partial response to escitalopram 20 mg, so augmentation preserves this benefit rather than discarding it 1
• Augmentation avoids discontinuation symptoms from stopping escitalopram 1
• The American College of Physicians found no significant difference between switching versus augmenting strategies overall, but augmentation is preferred when partial benefit exists 1

Additional Clinical Benefits

• Significantly lower sexual dysfunction rates compared with SSRIs (a common reason for treatment discontinuation) 1, 4
• Minimal weight gain or potential weight loss, unlike many antidepressants 1, 4
• Lower sedation rates than SSRIs, beneficial for older adults concerned about falls 3

Common Pitfalls to Avoid

• Do not skip the gradual titration in older adults—starting at full dose (150 mg) increases adverse event risk 1
• Do not exceed 300 mg/day total in older adults to maintain seizure risk at 0.1% 1
• Do not give the second dose after 3 PM, as this significantly increases insomnia risk 1
• Do not declare treatment failure before 6–8 weeks at therapeutic dose, though energy improvements may appear within 2–4 weeks 1
• Do not combine with MAOIs or initiate within 14 days of MAOI discontinuation 1

Expected Timeline

• Early improvement in energy and motivation may occur within 2–4 weeks 1
• Full antidepressant and anxiolytic effects typically emerge by 6–8 weeks 1
• If inadequate response at 8 weeks, consider dose increase to 300 mg/day (if tolerating 150 mg twice daily) or alternative augmentation strategies 1

Renal/Hepatic Considerations for Older Adults

• Renal impairment: Reduce total daily dose by 50% if eGFR < 90 mL/min; avoid entirely in end-stage renal disease 1
• Hepatic impairment: Maximum 150 mg daily in moderate-to-severe impairment 1
• Escitalopram does not require dose adjustment in renal impairment but consider reduction in hepatic disease 3