In an 80‑year‑old patient taking Wellbutrin (bupropion) 300 mg daily who remains depressed and anxious after increasing from 150 mg, should the bupropion dose be increased further or should an augmenting medication be added?

Augment with an SSRI Rather Than Increase Bupropion Dose

In an 80-year-old patient on bupropion 300 mg daily who remains depressed and anxious after one month, add an SSRI (such as escitalopram 10 mg or sertraline 50 mg) rather than increasing the bupropion dose further. 1, 2

Rationale for Augmentation Over Dose Escalation

Why Augmentation Is Preferred

• The patient has been on 300 mg for only one month—this is insufficient time to assess full therapeutic response. The American College of Physicians recommends allowing 6–8 weeks at an adequate dose before determining treatment response or modifying the regimen. 1, 2

• Augmenting bupropion with an SSRI demonstrates superior efficacy compared to other augmentation strategies when initial monotherapy fails, with STAR*D trial data showing remission rates of approximately 30% when citalopram was augmented with bupropion. 1

• Bupropion augmentation of SSRIs (or vice versa) shows significantly lower discontinuation rates (12.5%) compared to buspirone augmentation (20.6%, P < 0.001), indicating better tolerability while delivering comparable remission. 1

• The combination addresses both depression and anxiety through complementary mechanisms: bupropion works via noradrenergic/dopaminergic pathways while SSRIs target serotonin, providing broader neurotransmitter coverage for comorbid anxiety. 1

Why Not Increase Bupropion Dose

• The maximum recommended dose for bupropion SR in older adults is 150 mg twice daily (300 mg total daily), which this patient has already reached. 1

• The American Geriatrics Society recommends starting older adults at approximately 50% of standard adult doses (37.5 mg titrated gradually) due to increased risk of adverse reactions, and this patient is already at the upper limit for elderly dosing. 1

• Doses above 300 mg/day increase seizure risk, and while the maximum FDA-approved dose is 400 mg/day for SR formulation, this applies to younger adults without age-related pharmacokinetic changes. 1, 3

• Older adults have reduced renal clearance, and bupropion metabolites accumulate with age; the FDA label recommends dose reduction in renal impairment (GFR < 90 mL/min), which is common in 80-year-olds. 1, 3

Specific Augmentation Protocol

SSRI Selection and Dosing

• Start escitalopram 10 mg once daily in the morning OR sertraline 50 mg once daily in the morning while continuing bupropion 300 mg (150 mg twice daily). 1

• Escitalopram is preferred for prominent anxiety symptoms, as SSRIs are generally first-line for anxious depression, though the combination with bupropion remains safe and effective. 1

• No washout period is required when adding an SSRI to bupropion, as neither is an MAOI; immediate initiation is safe. 1

Timeline and Monitoring

• Continue the combination for a full 6–8 weeks before assessing adequacy of response, as this is the standard timeframe for all second-generation antidepressants. 1, 2

• Monitor within 1–2 weeks of adding the SSRI for therapeutic response, adverse effects, and emergence of agitation, irritability, or suicidal thoughts—particularly critical in the first 1–2 months when suicide risk is highest. 1, 2, 3

• Assess blood pressure and heart rate periodically, especially in the first 12 weeks, as bupropion can cause elevations in both parameters. 1, 2

Critical Safety Screening Before Augmentation

Absolute Contraindications to Verify

• Confirm no uncontrolled hypertension (≥140/90 mm Hg or ≥130/80 mm Hg in high-risk patients), as bupropion can elevate blood pressure and is contraindicated in uncontrolled hypertension. 1, 2

• Verify no history of seizure disorder, head trauma, brain metastases, or conditions lowering seizure threshold, as bupropion significantly lowers seizure threshold. 1, 2

• Confirm no current or recent MAOI use (within 14 days), as this is an absolute contraindication to both bupropion and SSRIs. 1, 2, 3

• Screen for eating disorders (bulimia or anorexia nervosa), which are absolute contraindications to bupropion due to higher seizure incidence. 1, 2

Renal Function Consideration

• Assess renal function (eGFR) in this 80-year-old patient; if GFR < 90 mL/min (moderate to severe impairment), the current bupropion dose of 300 mg may already be excessive and should be reduced by 50% to 150 mg daily before adding an SSRI. 1

Clinical Advantages of This Combination

Complementary Benefits

• Bupropion may counteract SSRI-induced sexual dysfunction, which occurs significantly less often with bupropion than with SSRIs like escitalopram and paroxetine. 1, 2

• Bupropion is associated with minimal weight gain or even weight loss, unlike many SSRIs, providing an advantage for older adults concerned about metabolic effects. 1

• The combination has lower rates of sedation compared to SSRI monotherapy, which is beneficial for older adults at risk for falls. 1

What to Do If Inadequate Response After 8 Weeks

Next Steps After Failed Combination

• If after 8 weeks of combined therapy (bupropion 300 mg + SSRI at therapeutic dose) there is insufficient response, add cognitive-behavioral therapy (CBT) rather than further increasing medication doses. 1

• Combination treatment of CBT plus medication is superior to either modality alone for depression, supported by moderate-strength evidence. 1

• Alternatively, consider switching to a different SSRI after failure of the first SSRI, which yields remission in roughly 21–25% of cases. 1

Common Pitfalls to Avoid

• Do not discontinue bupropion prematurely before 6–8 weeks at the current 300 mg dose unless significant adverse effects occur; one month is insufficient to declare treatment failure. 1

• Do not skip the intensive monitoring window during weeks 1–2 after adding the SSRI, as this period carries the highest risk for emergent suicidal ideation, particularly in patients under 24 years (though this patient is 80, vigilance remains important). 1, 3

• Do not exceed a total bupropion dose of 450 mg/day to maintain seizure risk at 0.1%, and in this 80-year-old, do not exceed 300 mg/day given age-related considerations. 1, 3

• Do not combine with tramadol, meperidine, methadone, fentanyl, dextromethorphan, or St. John's wort when adding an SSRI, as these increase serotonin syndrome risk. 1

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