What medications can be added or substituted for a woman in her late 80s with uncontrolled depression, anxiety, and panic attacks who is already taking bupropion 150 mg twice daily and a low‑dose bedtime sedative?

Augmentation Strategy for Treatment-Resistant Depression, Anxiety, and Panic in an Elderly Woman

Add an SSRI (sertraline 50 mg daily, titrated to 100–200 mg) to the existing bupropion 150 mg twice daily, rather than switching medications, because augmentation with an SSRI demonstrates superior efficacy and lower discontinuation rates compared to other strategies in treatment-resistant depression. 1

Why Augmentation Over Switching

The current bupropion regimen should be maintained and augmented rather than replaced because:

• Augmenting SSRIs with bupropion decreases depression severity more effectively than augmentation with buspirone, with significantly lower discontinuation rates (12.5% vs 20.6%, P < 0.001) 1
• The STAR*D trial showed that augmentation with bupropion achieved remission in approximately 30% of patients who failed initial SSRI monotherapy 1
• Switching to another antidepressant yields only 21–25% remission rates, making augmentation the preferred strategy 1

Specific SSRI Selection for This Patient

Sertraline is the optimal SSRI choice for augmentation in this elderly patient with anxiety and panic attacks because:

• Sertraline demonstrates better efficacy for managing psychomotor agitation compared to fluoxetine 2
• Head-to-head trials showed similar antidepressive efficacy among SSRIs when treating depression with comorbid anxiety symptoms 2
• Avoid paroxetine due to its high anticholinergic burden, which is particularly problematic in older adults per the American Geriatric Society's Beers Criteria 1
• Avoid fluoxetine because it carries greater risk of agitation and overstimulation in elderly patients 1

Dosing Protocol for Sertraline Augmentation

Start sertraline 50 mg once daily in the morning, then titrate to 100–200 mg based on response:

• Begin with 50 mg daily for 1 week to assess tolerability 1
• Increase to 100 mg daily after 1 week if well tolerated 1
• Further titration to 150–200 mg may be needed for optimal response 1
• Allow 6–8 weeks at therapeutic doses before declaring treatment failure 1

Critical Safety Screening Before Adding Sertraline

Verify the following contraindications are absent:

• No MAOI use within the preceding 14 days (risk of serotonin syndrome within 24–48 hours) 1
• No concurrent serotonergic agents (tramadol, meperidine, methadone, fentanyl, dextromethorphan, St. John's wort) 1
• Baseline QT interval assessment, as escitalopram can prolong QT at higher doses 1
• Blood pressure must be controlled, as bupropion can elevate BP and heart rate 1

Monitoring During the First 8 Weeks

Intensive monitoring is mandatory in the early treatment phase:

• Weeks 1–2: Assess for suicidal ideation, agitation, irritability, or unusual behavioral changes (highest risk period for suicide attempts) 1
• Weeks 1–2: Monitor for early serotonin syndrome signs: mental-status changes, neuromuscular hyperactivity (tremor, clonus), autonomic hyperactivity (hypertension, tachycardia, diaphoresis) 1
• First 12 weeks: Monitor blood pressure and heart rate periodically, as bupropion can cause elevations 1
• Week 6–8: Formal efficacy assessment; if inadequate response, consider dose adjustment or adding cognitive-behavioral therapy 1

Alternative Augmentation if SSRI Fails or Is Contraindicated

If sertraline augmentation is ineffective after 8 weeks or contraindicated, consider:

1. Aripiprazole augmentation (2–5 mg daily) is particularly effective for persistent energy, motivation, and apathy deficits despite optimized bupropion 1
2. Mirtazapine (7.5–15 mg at bedtime) may address insomnia and anxiety while providing antidepressant augmentation 2

Specific Advantages of This Combination for the Patient

The bupropion-sertraline combination offers unique benefits:

• Addresses depression through complementary mechanisms: sertraline affects serotonin while bupropion works via noradrenergic/dopaminergic pathways 1
• Bupropion significantly reduces SSRI-induced sexual dysfunction (a common SSRI side effect) 1, 3
• Bupropion is associated with minimal weight gain or even weight loss, offsetting potential SSRI weight effects 1, 3
• Both medications are safe and effective in patients aged >65 years when dosed appropriately 1, 4

Critical Pitfalls to Avoid

• Do not discontinue bupropion prematurely before 6–8 weeks at therapeutic doses unless significant adverse effects occur 1
• Do not exceed bupropion 300 mg/day total (current dose of 150 mg twice daily is at maximum) to maintain seizure risk at 0.1% 1
• Do not skip the intensive monitoring window during weeks 1–2, as this period carries the highest risk for emergent suicidal ideation 1
• Do not administer the second bupropion dose after 3 PM to minimize insomnia risk 1
• Do not combine with MAOIs or initiate within 14 days of MAOI discontinuation 1

Expected Timeline for Clinical Response

• Early improvement in energy levels may occur within the first few weeks with bupropion 1
• Full antidepressant and anxiolytic effects typically emerge 6–8 weeks after achieving therapeutic dosing 1
• If no adequate response by 6–8 weeks, add cognitive-behavioral therapy rather than further increasing medication doses 1
• After achieving remission, continue treatment for at least 4–9 months for first-episode depression, or ≥1 year for recurrent depression 1