Can a patient in their late 50s with a history of depression, who has stopped smoking and is experiencing increased anxiety, be prescribed bupropion while currently taking Prozac (fluoxetine)?

Can This Patient Use Bupropion with Prozac?

Yes, bupropion can be added to Prozac (fluoxetine) in this patient, and this combination is actually a well-established augmentation strategy for depression that has failed to respond adequately to SSRI monotherapy. 1, 2

Rationale for Combination Therapy

The combination of bupropion and an SSRI like Prozac addresses depression through complementary mechanisms—Prozac affects serotonin pathways while bupropion works via noradrenergic and dopaminergic pathways. 2 This augmentation strategy is supported by evidence showing:

• Low-quality evidence demonstrates that augmenting SSRIs with bupropion decreases depression severity more effectively than augmentation with buspirone. 1
• When citalopram (another SSRI) was augmented with bupropion versus buspirone, bupropion showed significantly lower discontinuation rates due to adverse events (12.5% vs. 20.6%, P < 0.001). 2
• Augmentation with bupropion is equally effective as switching to another antidepressant, but may be preferred to avoid SSRI discontinuation symptoms. 2

Specific Benefits for This Patient

This patient has three clinical features that make bupropion particularly advantageous:

• Former smoker with increased anxiety: Bupropion is FDA-approved for smoking cessation and may help prevent relapse to smoking during this stressful period. 3, 4
• History of depression: Bupropion may be particularly beneficial for patients with comorbid depression and smoking cessation needs, addressing both conditions simultaneously. 2, 3
• Age in late 50s: This patient requires careful dosing but has no age-related contraindication. 2

Dosing Protocol

Start with bupropion SR 150 mg once daily in the morning for 3 days, then increase to 150 mg twice daily (300 mg total daily dose) if tolerated. 2 The specific timing is critical:

• First dose: Morning 2
• Second dose: Before 3 PM to minimize insomnia risk 2
• Maximum dose: 300 mg/day for this indication (do not exceed to maintain seizure risk at 0.1%) 2, 3

For older adults in their late 50s, consider starting even lower at 37.5 mg every morning and gradually increasing by 37.5 mg every 3 days as tolerated. 2

Critical Safety Screening Required

Before prescribing, you must screen for absolute contraindications:

• Seizure history or any condition predisposing to seizures (brain tumor, stroke, head trauma, epilepsy) 1, 3, 4
• Current or recent MAOI use (within 14 days) 2, 4
• Eating disorders (bulimia or anorexia nervosa) due to increased seizure risk 2
• Abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs 2, 4
• Uncontrolled hypertension 2, 4
• Moderate to severe hepatic or renal impairment (requires dose reduction) 2, 3

Monitoring Parameters

Begin monitoring within 1-2 weeks of initiation, focusing on: 3

• Blood pressure and heart rate (especially first 12 weeks, as bupropion can elevate both) 2, 4
• Neuropsychiatric symptoms: agitation, restlessness, behavioral changes, worsening anxiety 1, 2, 3
• Suicidal ideation (particularly critical in patients under 24 years, though this patient is older) 2, 3
• Seizure risk factors (the seizure risk at 300 mg/day is approximately 0.1% or 1 in 1,000) 1, 2

Expected Timeline

• Early effects: Energy levels may improve within the first few weeks 2
• Full assessment: Allow 6-8 weeks at an adequate dose before determining treatment response 2, 3
• Anxiety monitoring: The patient's increased anxiety warrants close attention, as bupropion has activating properties that could theoretically worsen anxiety initially, though this is not a contraindication 2

Common Pitfalls to Avoid

Do not exceed 300 mg/day total dose when using bupropion for depression augmentation or smoking cessation maintenance, as higher doses significantly increase seizure risk. 2, 3 The maximum dose of 450 mg/day for depression applies only to specific formulations and clinical scenarios not relevant here. 4

Do not administer the second dose late in the day—the cutoff is 3 PM to prevent insomnia, which could worsen the patient's anxiety. 2

Do not confuse bupropion monotherapy with naltrexone-bupropion combination products—if the patient were on opioids (including Suboxone), the combination product would be absolutely contraindicated, but bupropion alone does not have this restriction. 2

Addressing the Anxiety Component

While bupropion's activating properties might seem counterintuitive for a patient with increased anxiety, the evidence does not show that comorbid anxiety significantly affects bupropion's comparative efficacy in depression. 2 The anxiety may actually be a symptom of inadequately treated depression or nicotine withdrawal from recent smoking cessation. Monitor closely, and if anxiety worsens significantly, consider:

• Ensuring the Prozac dose is optimized
• Behavioral interventions for anxiety
• Reassessing after 2-4 weeks, as initial activation often subsides

Drug Interaction Considerations

The combination of fluoxetine and bupropion does not have significant pharmacokinetic interactions that would preclude their use together. 1 However, both medications can lower seizure threshold, so adherence to maximum dosing guidelines is essential. 1, 3