What are the taper directions for Rexulti (brexpiprazole)?

Rexulti (Brexpiprazole) Tapering Directions

There are no established, evidence-based tapering protocols specifically for Rexulti (brexpiprazole), but based on general antipsychotic tapering principles and the drug's pharmacology, a gradual taper over 8-16 weeks with dose reductions of 0.5mg every 2-4 weeks is recommended, never discontinuing abruptly.

Critical Safety Principles

• Abrupt discontinuation of Rexulti is unacceptable medical care and can precipitate severe withdrawal symptoms including insomnia, anxiety, irritability, and rapid symptom destabilization 1
• Sudden cessation of antipsychotics carries significant morbidity risk, similar to abruptly stopping antihypertensives or antihyperglycemics 1
• Patient collaboration is essential—ensure the patient understands the plan, agrees with the pace, and knows they can request slower tapering if needed 1

Recommended Tapering Schedule

Standard Taper Protocol

• Begin with 0.5mg reductions every 2-4 weeks until reaching the lowest feasible dose 2
• The entire tapering process typically takes 8-16 weeks to complete 2
• Each new dose should be maintained for the full 2-4 week period before the next reduction 2

Dose Reduction Strategy

• Start from the current dose (typically 2-4mg/day for schizophrenia) 3, 4
• Reduce by 0.5mg increments (e.g., 4mg → 3.5mg → 3mg → 2.5mg → 2mg → 1.5mg → 1mg → 0.5mg → discontinue) 2
• Do not use alternate-day dosing as this creates significant receptor occupancy variation and increases withdrawal risk 5

If Withdrawal Symptoms Occur

• Immediately return to the previous dose and maintain until symptoms stabilize 1, 2
• Consider smaller dose reductions of 0.25mg instead of 0.5mg 2
• Extend the time between dose reductions to 4-6 weeks rather than 2-4 weeks 2
• The taper rate must be determined by the patient's ability to tolerate it, not a predetermined schedule 1

Monitoring Requirements

• Schedule follow-up appointments every 2-4 weeks during the taper to assess for withdrawal symptoms and return of original psychiatric symptoms 2
• Document baseline symptoms and functioning before initiating the taper 2
• Monitor specifically for: insomnia, anxiety, irritability, akathisia, and exacerbation of psychotic or mood symptoms 2

Managing Withdrawal Symptoms

• Consider adjunctive medications to manage specific withdrawal symptoms (e.g., trazodone for insomnia, clonidine for autonomic symptoms) 2, 6
• Provide adequate clinician support and availability throughout the tapering process 1
• Ensure access to urgent psychiatric care if acute decompensation occurs 2

Common Pitfalls to Avoid

• Never make "cold referrals" to other clinicians during the taper without ensuring they have agreed to accept the patient's care 1, 2
• Do not abandon the patient if they struggle with the taper—consider pausing at a stable dose rather than pushing forward 2
• Avoid using a fixed timeline; the taper must be adjusted based on individual response 1, 2
• Do not assume withdrawal symptoms represent disease relapse without careful assessment 2

Special Considerations for Brexpiprazole

• Brexpiprazole has a half-life of approximately 91 hours, meaning steady-state changes occur slowly after dose adjustments 3
• The drug's partial agonist activity at D2 receptors (lower intrinsic activity than aripiprazole) may theoretically reduce withdrawal severity, but this has not been clinically validated 3
• Akathisia occurs in 5.5% of patients during treatment, so distinguishing akathisia from withdrawal symptoms during tapering is important 4

When Tapering May Not Be Necessary

• Patients taking Rexulti less than once daily do not need a formal taper 1
• However, given the drug's long half-life, this scenario is unlikely with standard dosing