Additional Medication Options for Treatment-Resistant Depression
Given your current regimen of escitalopram 20mg, bupropion 150mg XL, and Rexulti 1mg, you can safely increase the bupropion dose to optimize your current combination therapy before adding additional agents. 1, 2
Optimizing Current Medications First
Bupropion Dose Escalation
- Your bupropion 150mg XL is below the therapeutic target dose of 300mg daily for depression. 1
- The standard titration is 150mg once daily initially, then increasing to 300mg once daily (the typical maintenance dose for depression). 1
- Maximum dose is 450mg daily for XL formulation, though 300mg is usually sufficient. 1
- Increase to 300mg XL once daily in the morning, as this dose has been studied in combination with escitalopram and is well-tolerated. 3, 4
Safety of Your Current Combination
- The combination of escitalopram and bupropion is commonly used, well-studied, and safe. 3, 4
- Studies show remission rates of 50-62% with this combination at therapeutic doses (escitalopram 20mg + bupropion up to 400mg SR equivalent). 4
- No contraindications exist between bupropion and SSRIs like escitalopram. 5, 2
- Adding Rexulti (brexpiprazole) as an augmentation agent to this combination is FDA-approved for treatment-resistant depression. 5
Critical Drug Interaction Considerations
What to Monitor
- Bupropion inhibits CYP2D6, which can increase escitalopram levels modestly, but this is not clinically significant at standard doses. 2, 6
- Escitalopram has minimal effect on CYP enzymes and low drug interaction potential. 7, 6
- Administer bupropion in the morning and ensure any second dose (if switching to SR formulation) is given before 3 PM to minimize insomnia. 1
Absolute Contraindications to Avoid
- Never combine with MAOIs (monoamine oxidase inhibitors) or within 14 days of stopping MAOIs due to hypertensive crisis risk. 5, 1, 2
- Avoid adding tramadol, meperidine, or other serotonergic opioids due to serotonin syndrome risk with escitalopram. 5
- Do not add medications that lower seizure threshold (bupropion already does this). 2
If Further Augmentation is Needed
After Optimizing Bupropion Dose
If inadequate response persists after increasing bupropion to 300mg daily for 6-8 weeks: 1
Additional augmentation options include:
- Increasing Rexulti dose (can go up to 2-3mg daily for depression augmentation, though 1-2mg is typical). 5
- Adding lithium (requires blood level monitoring).
- Adding thyroid hormone (T3) for augmentation.
- Switching to a different antidepressant class rather than adding more medications.
Monitoring Requirements
- Watch for increased agitation or activation, as bupropion is an activating medication. 1
- Monitor blood pressure, as bupropion can elevate BP and should be avoided in uncontrolled hypertension. 1, 2
- Screen for seizure risk factors (eating disorders, alcohol withdrawal, head trauma history) as bupropion lowers seizure threshold. 1, 2
- Monitor for serotonin syndrome symptoms if any serotonergic agents are added: agitation, confusion, tremor, hyperreflexia, diaphoresis, fever. 5
Practical Next Steps
The most evidence-based approach is to increase bupropion XL from 150mg to 300mg once daily in the morning. 1, 4 This optimizes your current regimen before considering additional medications, as your bupropion dose is subtherapeutic. Studies specifically examining escitalopram 20mg combined with bupropion 300-400mg show this is safe and more effective than either monotherapy. 3, 4