What medication change is recommended for a patient on Latuda (lurasidone) 40 mg daily, Buspar (buspirone) 20mg BID, and Trintellix (vortioxetine) 20 mg daily who is still experiencing depression?

Medication Management for Persistent Depression

For a patient on Latuda 40 mg daily, Buspar 20mg BID, and Trintellix 20 mg daily who is still experiencing depression, I recommend augmenting with bupropion as the most effective next step to improve depressive symptoms.

Current Medication Analysis

The patient is currently on:

• Latuda (lurasidone) 40 mg daily - an atypical antipsychotic
• Buspar (buspirone) 20 mg BID - an anxiolytic
• Trintellix (vortioxetine) 20 mg daily - an antidepressant

This combination suggests treatment for both depression and anxiety symptoms, possibly with bipolar features or psychotic symptoms given the Latuda prescription.

Recommended Medication Changes

Primary Recommendation

1. Add bupropion - Low-quality evidence shows that augmentation with bupropion decreases depression severity more effectively than augmentation with buspirone 1. Bupropion is particularly beneficial as it:
   • Has an activating effect that can reduce apathy
   • Has lower rates of sexual side effects than other antidepressants
   • Works through a different mechanism (dopaminergic) than Trintellix (serotonergic)

Alternative Options (if bupropion is contraindicated)

1. Increase Latuda dosage - If bipolar depression is present, increasing Latuda to 60-80 mg may be beneficial. Research shows Latuda is effective as adjunctive therapy with mood stabilizers for bipolar depression 2.

2. Switch from Trintellix to another antidepressant - Moderate-quality evidence shows no difference in response when switching from one antidepressant to another, but individual responses may vary 1.

3. Add cognitive behavioral therapy (CBT) - Low-quality evidence shows no difference in response or remission when augmenting with another medication versus augmenting with cognitive therapy 1.

Implementation Plan

1. Add bupropion starting at 37.5 mg every morning
2. Increase by 37.5 mg every 3 days
3. Target dose: 150 mg twice daily
4. Important: Administer second dose before 3 pm to minimize insomnia risk

Monitoring and Follow-up

• Schedule follow-up within 1-2 weeks of medication change
• Monitor for:
  • Improvement in depressive symptoms
  • Potential side effects: insomnia, agitation, seizures (rare)
  • Serotonin syndrome risk with combined serotonergic medications (Trintellix + Buspar)

Important Considerations and Cautions

• Serotonin syndrome risk: The combination of multiple serotonergic agents (Trintellix, Buspar, and potentially bupropion) increases risk for serotonin syndrome 3. Monitor for signs including mental status changes, autonomic instability, neuromuscular symptoms, and gastrointestinal symptoms.

• Seizure risk: Bupropion should not be used in patients with seizure disorders 1.

• Bipolar disorder consideration: If the patient has bipolar disorder, antidepressant augmentation requires careful monitoring as it may trigger manic episodes. In this case, increasing Latuda may be preferred.

• Activating effects: Bupropion is activating and may rapidly improve energy levels, which could be particularly beneficial for this patient's persistent depression 1.

• Timing of doses: To minimize insomnia risk with bupropion, ensure the second daily dose is taken before 3 pm 1.

This approach targets the persistent depression while maintaining the current regimen that may be partially effective, adding a medication with a complementary mechanism of action to address the remaining symptoms.