What is a recommended tapering schedule for Vraylar (cariprazine)?

Recommended Tapering Schedule for Vraylar (Cariprazine)

A gradual tapering approach is recommended for Vraylar (cariprazine) discontinuation, with reductions of approximately 25% of the current dose every 2 weeks to minimize withdrawal symptoms and risk of symptom recurrence. 1

Understanding Vraylar's Unique Pharmacology

• Vraylar has an extremely long half-life, with the active metabolite didesmethyl-cariprazine having a half-life of 2-3 weeks, meaning changes in dose will not be fully reflected in plasma for several weeks 2, 3
• The FDA label specifically notes that after discontinuation, plasma concentration of cariprazine and its active metabolites will only decline by 50% in approximately 1 week 2
• Due to this prolonged elimination, withdrawal symptoms may be delayed compared to other antipsychotics, requiring careful monitoring throughout the tapering process 2, 4

Recommended Tapering Protocol

For patients on 3 mg daily:

• Weeks 1-2: Continue current dose of 3 mg daily
• Weeks 3-4: Reduce to 1.5 mg daily (50% reduction)
• Weeks 5-6: Reduce to 1.5 mg every other day
• Weeks 7-8: Discontinue

For patients on 1.5 mg daily:

• Weeks 1-2: Continue current dose of 1.5 mg daily
• Weeks 3-4: Reduce to 1.5 mg every other day
• Weeks 5-6: Reduce to 1.5 mg every third day
• Weeks 7-8: Discontinue

Monitoring During Tapering

• Schedule follow-up appointments at least monthly during the tapering process to assess for withdrawal symptoms or clinical deterioration 1
• Monitor for return of psychiatric symptoms, which may not appear immediately but could manifest weeks after dose reduction due to the long half-life of cariprazine 2, 4
• Pay particular attention to sleep disturbances, mood changes, anxiety, and psychotic symptoms that may indicate a need to slow the taper 1

Special Considerations

• For patients on higher doses (4.5-6 mg), consider a more gradual approach with smaller incremental reductions (e.g., 6 mg → 4.5 mg → 3 mg → 1.5 mg → 1.5 mg every other day) 1, 5
• If transitioning to another antipsychotic, consider overlapping medications during the taper to maintain symptom control 6
• If symptoms worsen during tapering, return to the previous well-tolerated dose and attempt a slower taper with smaller dose reductions 6, 5

Evidence-Based Rationale

• Studies on antipsychotic tapering suggest that more gradual tapering (over months) in a hyperbolic manner may reduce the risk of relapse by allowing neuroadaptations time to resolve 5
• The American Academy of Child and Adolescent Psychiatry recommends gradual tapering over abrupt discontinuation to reduce withdrawal symptoms and symptom recurrence 1
• The FDA label acknowledges that "the decline in plasma concentrations of active drug and metabolites may not be immediately reflected in patients' clinical symptoms" after discontinuation 2

Common Pitfalls to Avoid

• Avoid tapering too quickly, as this may increase the risk of withdrawal symptoms and relapse 6, 5
• Do not underestimate the long half-life of cariprazine's active metabolites; symptoms may appear weeks after dose reduction 2, 3
• Remember that the final doses before complete cessation may need to be very small to prevent a large decrease in receptor blockade when stopped 5
• Avoid abrupt discontinuation, which can increase the risk of rebound symptoms and relapse 1, 6