Adding Bupropion to Sertraline and Risperidone in Treatment-Resistant Depression
Direct Answer
Yes, bupropion (Wellbutrin) can be added to this patient's current regimen of sertraline 100mg and risperidone 2mg, as augmentation with bupropion has demonstrated superior efficacy in reducing depression severity compared to other augmentation strategies in treatment-resistant depression. 1
Evidence-Based Rationale
Bupropion as an Augmentation Strategy
Augmentation with bupropion decreases depression severity more than augmentation with buspirone, with lower discontinuation rates due to adverse events in patients who have failed initial SSRI treatment 2, 1
The American College of Physicians found no difference in response or remission rates when augmenting citalopram with bupropion versus buspirone, but bupropion showed superior reduction in depression severity scores 2
Multiple case reports and case series demonstrate successful combination therapy of SSRIs (including sertraline) with bupropion in treatment-refractory major depression, with synergistic effects on depressive symptoms 3, 4
Mechanism and Clinical Benefits
The combination of sertraline and bupropion provides complementary mechanisms: serotonergic activity from sertraline plus dopaminergic and noradrenergic activity from bupropion 4
This patient already has risperidone as an augmentation agent (an atypical antipsychotic), which aligns with National Institute of Mental Health recommendations for partial responders 1
Adding bupropion provides an additional mechanistic approach beyond the current SSRI-antipsychotic combination 3
Safety Considerations and Critical Warnings
Major caveat: There is documented risk of serotonin syndrome when combining bupropion with SSRIs, though this is rare 5
One case report described serotonin syndrome in a patient on therapeutic doses of bupropion and sertraline, attributed to bupropion's inhibition of cytochrome P450 2D6, which increases SSRI blood levels 5
Monitor closely for myoclonic jerks, confusion, agitation, autonomic instability, or altered consciousness—these may be misinterpreted as worsening depression 5
Bupropion lowers the seizure threshold; ensure this 69-year-old patient has no seizure risk factors and maintain total daily dose at or below 450mg in divided doses 6
Bupropion causes minimal anticholinergic effects and rare orthostatic hypotension, making it generally well-tolerated in elderly patients 6
Practical Implementation
Start bupropion at low doses (100mg once or twice daily) and titrate gradually over weeks to minimize seizure risk and allow assessment of tolerability 3, 6
Target dose typically ranges from 150-450mg daily in divided doses, with most treatment-resistant depression studies using 300-450mg daily 3, 4
Monitor response within 1-2 weeks of initiation and assess therapeutic response at 6-8 weeks, as recommended by the American College of Physicians for antidepressant modifications 2
Watch specifically for early signs of serotonin syndrome (myoclonus, confusion, autonomic changes) during the first few weeks after adding bupropion 5
Alternative Considerations
If bupropion augmentation fails or is not tolerated, the patient already has risperidone in place, which represents guideline-concordant augmentation with an atypical antipsychotic 1. The next steps would include optimizing risperidone dosing, considering lithium augmentation (requires monitoring), or exploring non-pharmacological options like cognitive behavioral therapy or electroconvulsive therapy 1.