What is the recommended protocol for transitioning a patient from Rexulti (brexpiprazole) to Vraylar (cariprazine) for augmentation of sertraline in the treatment of major depressive disorder?

Transitioning from Rexulti to Vraylar for Augmentation of Sertraline in Major Depressive Disorder

When transitioning from Rexulti (brexpiprazole) to Vraylar (cariprazine) for augmentation of sertraline in major depressive disorder, implement a cross-titration approach with a 1-2 week overlap period rather than abrupt discontinuation to minimize withdrawal effects and maintain therapeutic efficacy.

Rationale for Switching Between Atypical Antipsychotics

Atypical antipsychotics are effective augmentation strategies for patients with major depressive disorder who have had an inadequate response to antidepressant monotherapy. Recent evidence suggests that failure to respond to one atypical antipsychotic does not preclude response to another, with studies showing that patients who failed to respond to a first augmentation trial with one atypical antipsychotic (including brexpiprazole) may still respond to cariprazine as a second augmentation agent 1.

Cross-Titration Protocol

1. Initial Assessment:

   • Confirm inadequate response to sertraline plus Rexulti combination (defined as <50% reduction in depressive symptoms after 6-8 weeks of adequate dosing) 2, 3
   • Document baseline symptoms, side effects, and vital signs

2. Cross-Titration Schedule:

   • Week 1: Start Vraylar at 1.5 mg/day while maintaining current Rexulti dose
   • Week 2: Increase Vraylar to 3 mg/day while reducing Rexulti by 50%
   • Week 3: Discontinue Rexulti completely and maintain Vraylar at 3 mg/day
   • Week 4 and beyond: Adjust Vraylar dose as needed (therapeutic range 1.5-3 mg/day for MDD augmentation)

3. Sertraline Management:

   • Maintain stable sertraline dosing throughout the transition period
   • Standard therapeutic dosing of sertraline (50-200 mg/day) should be continued 2, 4

Monitoring During Transition

• Timing: Assess patient status, therapeutic response, and adverse effects within 1-2 weeks of initiating the medication change 2
• Frequency: Weekly monitoring during the cross-titration period
• Parameters to monitor:
  • Depressive symptoms (using standardized scales)
  • Emergence of akathisia (common with both medications)
  • Metabolic parameters (weight, blood pressure, glucose)
  • Extrapyramidal symptoms
  • Suicidal thoughts (highest risk during first 1-2 months of treatment changes) 2

Potential Challenges and Solutions

Overlapping Side Effect Profiles

Both medications can cause:

• Akathisia
• Weight gain
• Metabolic changes

Solution: Monitor closely and adjust dosing as needed. Consider lower initial doses of Vraylar if akathisia was problematic with Rexulti.

Pharmacokinetic Differences

• Vraylar has a significantly longer half-life than Rexulti
• Active metabolites of Vraylar can persist for weeks

Solution: Allow adequate time (4-6 weeks) to assess full response to Vraylar after completing the transition.

Assessment of Treatment Response

• Evaluate response to the new regimen within 6-8 weeks of completing the transition 2, 3
• If inadequate response after 8 weeks of optimized Vraylar dosing, consider alternative augmentation strategies or switching approaches 2

Important Considerations

• Avoid abrupt discontinuation of Rexulti to prevent withdrawal symptoms
• Maintain consistent timing of medication administration throughout transition
• Document rationale for switch and response to previous augmentation trial
• Cariprazine has shown efficacy in patients who failed to respond to previous atypical antipsychotic augmentation, including brexpiprazole 1

This cross-titration approach balances the need to maintain therapeutic coverage while minimizing the risk of additive side effects during the transition from Rexulti to Vraylar for augmentation of sertraline in major depressive disorder.