Can bupropion be added to a patient who is taking citalopram 20 mg daily (and not sertraline), and what is the appropriate starting dose?

Can Bupropion Be Added to Citalopram 20 mg?

Yes, bupropion can be safely added to citalopram 20 mg daily, and the recommended starting dose is 150 mg once daily in the morning for the first 3 days, then increase to 150 mg twice daily if tolerated. 1

Starting Dose and Titration

The standard bupropion dosing when combining with an SSRI like citalopram follows this schedule 1, 2:

• Days 1-3: 150 mg orally once daily in the morning
• Day 4 onward: 150 mg orally twice daily (if tolerated)
• Maximum dose: 300 mg per day total

Give the second dose before 3 p.m. to minimize insomnia risk 1. This is particularly important since bupropion has activating properties.

Evidence Supporting This Combination

Multiple studies demonstrate that combining citalopram with bupropion is both effective and well-tolerated:

• A naturalistic cohort study showed that combining citalopram and bupropion-SR was superior to switching medications in treatment-resistant depression, with 28% achieving remission versus 7% with monotherapy switching 3
• An open pilot study of escitalopram (closely related to citalopram) plus bupropion-SR achieved 50% remission rates with only 6% discontinuing due to side effects 4
• Isobolographic analysis demonstrates synergistic antidepressant effects when combining citalopram with bupropion 5, 6

Safety Considerations

Drug Interactions

Bupropion is a moderate CYP2D6 inhibitor 2, 7, while citalopram has minimal effect on CYP450 enzymes 8. This combination does not create significant metabolic drug interactions between the two medications themselves.

QT Prolongation Concerns

Citalopram can prolong the QT interval, particularly at doses above 40 mg/day 8, 9. However:

• At 20 mg/day, the risk is minimal
• A cross-sectional study found no significant QTc prolongation with citalopram at therapeutic doses 10
• Bupropion does not appear to have a "QTc-sparing" effect when combined with citalopram 10

Contraindications for Bupropion

Do not use bupropion if the patient has 2:

• Seizure disorder or history of seizures (bupropion lowers seizure threshold)
• Brain metastases or stroke
• Taking MAO inhibitors (wait 14 days after MAOI discontinuation)
• Closed-angle glaucoma
• Concurrent use of tamoxifen

Monitoring Requirements

• Monitor for neuropsychiatric symptoms (depression worsening, suicidal ideation, agitation) in the first few weeks, though these are uncommon 2
• Assess blood pressure, as bupropion can cause mild increases
• Watch for insomnia and adjust timing of second dose if needed

Clinical Advantages of This Combination

This combination is particularly useful when 11, 3:

• The patient has inadequate response to citalopram monotherapy
• The patient experiences SSRI-associated sexual dysfunction (bupropion can reverse this)
• The patient has low energy or apathy (bupropion's activating properties help)
• The patient needs smoking cessation support (bupropion is FDA-approved for this) 2

Common Pitfalls to Avoid

1. Don't start both medications simultaneously - The patient is already on citalopram, so simply add bupropion
2. Don't give the second bupropion dose late in the day - This causes insomnia
3. Don't use in agitated patients - Bupropion's activating properties can worsen agitation 1
4. Don't exceed 300 mg/day total bupropion when combining with SSRIs 1

Duration and Reassessment

After 4-8 weeks on the combination, reassess response 1. If the patient achieves remission, continue for at least 6-9 months before considering dose reduction 9. The combination is generally well-tolerated for long-term use 4, 11.