Adding Bupropion to Escitalopram and Lamotrigine for Depression
Yes, bupropion (Wellbutrin) can be safely added to escitalopram (Lexapro) and lamotrigine for treatment-refractory depression, with evidence supporting this combination's efficacy and tolerability. 1
Evidence for Combination Therapy
The combination of an SSRI (escitalopram) with bupropion is well-established for treatment-resistant depression:
A pilot study specifically evaluating escitalopram plus bupropion-SR demonstrated a 62% response rate and 50% remission rate in patients with chronic or recurrent major depressive disorder, significantly higher than typical SSRI monotherapy outcomes. 1
Only 6% of patients discontinued due to side effects, indicating excellent tolerability of this combination. 1
The combination addresses depression through complementary mechanisms: escitalopram affects serotonin pathways while bupropion works via noradrenergic and dopaminergic systems. 2
Specific Dosing Protocol
Start with conservative dosing and titrate gradually:
Begin bupropion SR at 150 mg once daily for 3 days, then increase to 150 mg twice daily (total 300 mg/day). 3
The first dose should be taken in the morning; the second dose must be taken before 3 PM to minimize insomnia risk. 3
Maximum dose is 400 mg/day for bupropion SR or 450 mg/day for bupropion XL formulations. 3
In the escitalopram-bupropion study, mean effective doses were escitalopram 18 mg/day and bupropion-SR 327 mg/day, achieved by weeks 6-8. 1
Critical Safety Considerations with Lamotrigine
Bupropion lowers the seizure threshold, which requires specific precautions when combined with lamotrigine (an antiepileptic drug):
The maximum dose of bupropion should not exceed 450 mg/day to minimize seizure risk. 3
Avoid this combination entirely if the patient has a history of seizure disorders, bulimia, or anorexia nervosa, as these conditions significantly increase seizure risk with bupropion. 4, 3
Monitor for any neurological symptoms, particularly in the first few months of treatment. 4
Monitoring Requirements
Implement systematic monitoring:
Blood pressure must be checked regularly, as bupropion can elevate blood pressure; avoid in patients with uncontrolled hypertension. 4, 3
Monitor for neuropsychiatric symptoms, especially in patients under 24 years old, due to bupropion's black box warning regarding suicidal ideation. 5
Watch for activating effects including agitation or insomnia, which may require dose adjustment or timing modification. 3
Special Clinical Advantages
This combination offers specific benefits:
Bupropion is particularly useful for patients with comorbid smoking habits, as it is FDA-approved for smoking cessation. 4
It may improve energy levels and reduce apathy in patients with depression characterized by low motivation. 3
Unlike SSRIs, bupropion does not cause sexual dysfunction, potentially improving overall tolerability. 6
Contraindications to Verify
Before initiating bupropion, confirm the patient does NOT have:
Current or recent (within 14 days) use of monoamine oxidase inhibitors (MAOIs). 4, 3
Requirement for chronic opioid therapy (if considering naltrexone-bupropion formulations). 4
Moderate to severe hepatic impairment (reduce dose to maximum 150 mg/day if present). 3
Moderate to severe renal impairment (reduce total daily dose by 50% if GFR <90 mL/min). 3
Bipolar Disorder Caveat
If there is any suspicion of bipolar disorder rather than unipolar depression, exercise extreme caution:
Bupropion can precipitate manic or hypomanic episodes in bipolar patients, even when stabilized on mood stabilizers like lamotrigine. 7
In one case series, 6 of 11 bipolar patients (55%) experienced manic episodes requiring bupropion discontinuation, including 5 patients stabilized on dual mood stabilizers. 7
However, case reports suggest bupropion may be maintained long-term in select bipolar patients when combined with adequate mood stabilization (lamotrigine plus venlafaxine in one case). 8
Monitor closely for mood elevation, decreased need for sleep, increased energy, or racing thoughts during the first 8-12 weeks. 7