In a 55‑year‑old woman on fluoxetine (Prozac) and bupropion with partial improvement, should risperidone be added for augmentation of depression?

Risperidone is NOT Recommended for Augmentation in This Case

For a 55-year-old woman on fluoxetine and bupropion with partial response to depression treatment, risperidone should not be added unless psychotic features are present. Antipsychotics like risperidone are indicated specifically for depression with psychosis, not for standard treatment-resistant depression 1.

Appropriate Next Steps for Partial Response

First: Optimize Current Regimen

• Continue the fluoxetine-bupropion combination, as this dual-mechanism approach (SSRI + NDRI) is evidence-based for treatment-resistant depression 1, 2
• Bupropion augmentation of SSRIs shows 60% full or partial response rates in patients with incomplete SSRI response 2, 3
• Ensure adequate dosing: bupropion up to 150 mg twice daily and fluoxetine up to 20 mg daily 1

Second: Consider Alternative Augmentation Strategies

If symptoms persist after optimizing current medications:

Switch Strategy:

• Switch to venlafaxine extended-release, sertraline, or duloxetine 1
• The STAR*D trial showed 25% remission rates when switching antidepressants in treatment-resistant cases, with no significant difference between agents 1

Augmentation Strategy (if switching is not preferred):

• Add mirtazapine to the current regimen 1
• Studies show no difference between switching versus augmenting with mirtazapine 1
• Mirtazapine offers faster onset of action compared to SSRIs and addresses insomnia if present 1

Third: Evaluate for Specific Symptom Clusters

Target remaining symptoms with appropriate agents:

• For anxiety: Venlafaxine may be superior to fluoxetine 1
• For insomnia: Consider mirtazapine (7.5-30 mg at bedtime) which promotes sleep 1
• For psychomotor agitation: Sertraline shows better efficacy than fluoxetine 1

Critical Caveat: When Antipsychotics ARE Indicated

Risperidone or other antipsychotics should ONLY be added if:

• The patient exhibits psychotic features (delusions, hallucinations) 1
• Depression is classified as "severe with psychotic features" 4
• In such cases, concomitant antipsychotic medication is required 1

Important Safety Considerations

Drug Interaction Alert:

• The fluoxetine-bupropion combination carries risk of serotonin syndrome, though rare 5
• Monitor for myoclonic jerks, confusion, agitation, dysautonomia 5
• Bupropion inhibits cytochrome P450 2D6, potentially increasing SSRI levels 5

Monitoring Parameters:

• Assess response at 4 weeks; if no improvement, consider medication adjustment 2
• After 12 weeks on optimized therapy, if <5% symptom improvement, switch strategies 1
• Monitor for suicidality, particularly in younger adults, though this patient is 55 years old 1

Evidence Quality Note

The recommendation against routine antipsychotic augmentation is based on consistent guideline evidence 1. The most recent high-quality evidence (2023 American College of Physicians guideline) shows no superiority of antipsychotic augmentation over other strategies in non-psychotic depression 1. Bupropion augmentation specifically shows decreased risk of requiring antipsychotic augmentation compared to other antidepressants 4.