Is the combination of Cymbalta (duloxetine) and Latuda (lurasidone) effective for treating depression?

Effectiveness of Cymbalta (Duloxetine) and Latuda (Lurasidone) Combination for Depression

The combination of Cymbalta (duloxetine) and Latuda (lurasidone) can be effective for treating depression, particularly in cases of bipolar depression or treatment-resistant major depressive disorder, though evidence specifically for this combination is limited.

Evidence for Individual Medications

Duloxetine (Cymbalta)

• Duloxetine is an SSNRI (selective serotonin norepinephrine reuptake inhibitor) with established efficacy for major depressive disorder 1
• It has shown consistent efficacy in painful diabetic peripheral neuropathy, with effectiveness sustained for 1 year in open-label trials 1
• Duloxetine dosing is relatively simple, with 60 mg once daily appearing to be as effective as 60 mg twice daily 1
• Common side effects include nausea, which can be reduced by starting at 30 mg daily for one week before increasing to 60 mg 1

Lurasidone (Latuda)

• Lurasidone is FDA-approved for bipolar I depression as both monotherapy and adjunctive therapy with lithium or valproate 2
• It has clinically meaningful treatment effect sizes for improvement in bipolar depression compared to placebo (0.51 as monotherapy, 0.34 as adjunctive therapy) 2
• The number needed to treat (NNT) for response with lurasidone monotherapy is 5, and for remission is 6-7 3
• Lurasidone has a favorable side effect profile with minimal effects on weight or metabolic parameters compared to other atypical antipsychotics 4, 3

Evidence for Combination Therapy

While there are no specific studies examining the duloxetine-lurasidone combination directly:

1. Lurasidone has shown efficacy as an adjunctive treatment when combined with mood stabilizers (lithium or valproate) for bipolar depression 5

   • Larger antidepressant effects were observed when lurasidone was combined with lithium (effect size d=0.45) compared to valproate (effect size d=0.22) 5

2. Duloxetine has been studied in combination with other agents for treatment-resistant depression:

   • A small retrospective study of duloxetine combined with bupropion for treatment-resistant depression showed significant improvement in 90% of patients 6

Clinical Application Algorithm

For patients with depression:

1. Determine depression type:

   • For major depressive disorder (MDD): Start with duloxetine monotherapy (30mg daily for 1 week, then 60mg daily) 1
   • For bipolar depression: Start with lurasidone monotherapy (20-60mg daily) or combined with a mood stabilizer 2, 3

2. For inadequate response to initial therapy:

   • In MDD with partial response to duloxetine: Consider adding lurasidone 20-60mg daily
   • In bipolar depression with partial response to lurasidone: Ensure mood stabilization before considering duloxetine addition

3. Monitoring:

   • Assess response within 1-2 weeks of initiation or dose changes 1
   • Monitor for side effects: nausea, somnolence, akathisia (lurasidone), sexual dysfunction (duloxetine)
   • Evaluate metabolic parameters periodically, though lurasidone has minimal effects on weight and metabolic parameters 3

Important Considerations

• The combination may be particularly useful for patients with:

  • Treatment-resistant depression
  • Bipolar depression with anxiety features
  • Depression with psychomotor changes

• Caution is warranted in:

  • Young adults (increased risk of suicidality with antidepressants)
  • Patients with cardiovascular disease (monitor blood pressure with duloxetine)
  • Patients with renal insufficiency (dose adjustment may be needed)

• Potential drug interactions should be assessed, though both medications have relatively favorable interaction profiles

While the specific combination lacks robust evidence, the individual efficacy of each medication and evidence from similar combination approaches suggest this could be an effective strategy for certain patients with depression, particularly those with bipolar depression or treatment-resistant MDD.