What medication would you recommend for a patient with ongoing depressive symptoms on Latuda (lurasidone) 40 mg daily, buspirone 20mg bid, and Trintellix (vortioxetine) 20 mg daily, who dislikes Cymbalta (duloxetine)?

Medication Recommendation for Ongoing Depression

For a patient with ongoing depression on Latuda 40 mg, buspirone 20mg BID, and Trintellix 20 mg who dislikes Cymbalta, I recommend adding bupropion as the next medication option.

Current Medication Analysis

The patient is currently on:

• Latuda (lurasidone) 40 mg daily - an atypical antipsychotic
• Buspirone 20 mg twice daily - an anxiolytic
• Trintellix (vortioxetine) 20 mg daily - an antidepressant

Despite this regimen, the patient continues to experience depressive symptoms and has expressed dislike for Cymbalta (duloxetine).

Rationale for Bupropion

1. Unique Mechanism of Action: Bupropion primarily affects norepinephrine and dopamine neurotransmission 1, providing a different mechanism than the current serotonergic medications (Trintellix).

2. Favorable Side Effect Profile: Bupropion is associated with lower rates of sexual dysfunction compared to SSRIs 2, 1, which may be beneficial if sexual side effects are contributing to the patient's dislike of Cymbalta.

3. Complementary Effects: Adding bupropion can address symptoms that may not be adequately controlled by the current regimen, particularly fatigue, low energy, and anhedonia 1.

Dosing Recommendation

• Start with bupropion 37.5 mg every morning
• Increase by 37.5 mg every 3 days
• Target dose: 150 mg twice daily, with the second dose given before 3 PM to minimize insomnia risk 1

Monitoring and Precautions

• Seizure Risk: Bupropion should not be used in patients with seizure disorders 1
• Common Side Effects: Monitor for insomnia, dry mouth, headache, nausea 1
• Drug Interactions: Be aware of potential interactions with the current medication regimen
• Therapeutic Response: Effects may take 2-4 weeks to fully stabilize 1

Alternative Options if Bupropion is Contraindicated or Ineffective

1. Switch to a Different Antidepressant:

   • Sertraline (50-200 mg daily)
   • Citalopram (20-40 mg daily)
   • Mirtazapine (15-45 mg daily) 1

2. Augmentation with Cognitive Behavioral Therapy:

   • CBT has similar effectiveness to antidepressants with fewer adverse effects 1, 3
   • Lower relapse rates compared to medication alone 1

3. Consider Antipsychotic Adjustment:

   • If negative symptoms predominate, cariprazine or aripiprazole may be options 2
   • Low-dose amisulpride (50 mg twice daily) could be considered for negative symptoms 2

Important Considerations

• The American College of Physicians recommends either switching to or augmenting with cognitive behavioral therapy for patients who don't respond to initial treatment with an adequate dose of a second-generation antidepressant 3

• If the patient has moderate to severe depression, combination therapy with CBT and medication may be more effective than monotherapy 3

• Buspirone augmentation has shown efficacy in some patients who failed to respond to antidepressant monotherapy, with 59% of patients showing complete or partial remission when buspirone was added to SSRI treatment 4. Since the patient is already on buspirone, this augmentation strategy has been implemented but requires additional intervention.

By adding bupropion to the current regimen, we target multiple neurotransmitter systems while minimizing the risk of side effects that may have made Cymbalta unacceptable to the patient.