Can I increase the dose of Cymbalta (duloxetine) to 40mg and add Zyprexa (olanzapine) 5mg twice a day?

Dosage Adjustment for Duloxetine and Addition of Olanzapine

Increasing duloxetine to 40mg daily is appropriate, but adding olanzapine 5mg twice daily should be done with caution due to potential side effects and drug interactions. 1, 2, 3

Duloxetine Dosage Increase

• Duloxetine dosing should be increased gradually, with 30mg once daily for 1 week before increasing to 60mg once daily being the recommended titration schedule 1, 2
• Increasing from current dose to 40mg is reasonable as an intermediate step toward the therapeutic dose of 60mg daily 4
• Effect size analyses show that while duloxetine 40mg has minimum efficacy, the most notable gain in efficacy occurs between the 40-60mg/day dosage range 4
• Taking duloxetine with food can improve initial tolerability, especially when increasing the dose 5

Olanzapine Addition Considerations

• Olanzapine starting dose should be 2.5-5mg once daily (usually at bedtime), not twice daily as proposed 1, 3
• Twice daily dosing of olanzapine at 5mg (10mg total daily) exceeds the recommended starting dose and increases risk of side effects 1, 3
• Caution is warranted when combining olanzapine with other medications due to potential drug interactions 3
• Elderly patients or those with hepatic impairment should receive lower starting doses of olanzapine (2.5mg) 1

Potential Adverse Effects and Monitoring

• Olanzapine can cause significant side effects including:

  • Sedation and drowsiness 1, 3
  • Orthostatic hypotension 1, 3
  • Metabolic effects including weight gain 3
  • Rapidly developing hyperglycemia (can occur within days of initiation) 6

• Duloxetine's most common side effect is nausea, which can be reduced by:

  • Taking with food 5
  • Gradual dose titration 1, 5
  • Starting at lower doses 5

Recommended Approach

1. For Duloxetine:

   • Increase to 40mg daily as an intermediate step 4
   • Take with food to improve tolerability 5
   • Plan to reassess in 1-2 weeks for potential increase to 60mg daily (therapeutic dose) 1, 4

2. For Olanzapine:

   • Start with 2.5mg once daily at bedtime instead of 5mg twice daily 1, 3
   • Monitor for sedation, orthostatic hypotension, and metabolic effects 1, 3
   • Check blood glucose within 3-5 days of initiation due to risk of rapid hyperglycemia 6
   • Increase gradually based on response and tolerability 1

3. Monitoring:

   • Assess for drug interactions between duloxetine and olanzapine 2, 3
   • Monitor for excessive sedation when combining these medications 1, 3
   • Regular weight monitoring is essential 3
   • Blood glucose monitoring is recommended, especially in the first week 6

Important Cautions

• Combining olanzapine with benzodiazepines has been associated with fatalities due to respiratory depression 1
• Olanzapine may cause QT prolongation, especially when combined with other medications 3
• Duloxetine has drug interactions with inhibitors of CYP1A2 and CYP2D6 2
• Both medications can cause sedation, potentially having an additive effect 1, 3