Discontinuing Rexulti (Brexpiprazole)
Brexpiprazole should be tapered gradually over 2-4 weeks minimum rather than discontinued abruptly, following the same principles established for other atypical antipsychotics, with close monitoring for symptom recurrence extending weeks to months after the final dose.
Evidence-Based Discontinuation Protocol
Pre-Discontinuation Assessment
Obtain comprehensive psychiatric history including previous symptom severity, response to brexpiprazole, reasons for discontinuation, and any prior relapse patterns when medications were stopped 1.
Review medical records and consult previous prescribers to understand the full clinical picture, as patients and families may not accurately recall the severity of symptoms that prompted treatment 1.
Assess current stability including duration of symptom remission, psychosocial functioning, and environmental stressors that could increase relapse risk 1.
Gradual Tapering Strategy
Taper brexpiprazole slowly over 2-4 weeks minimum, reducing by approximately 25% of the original dose every 1-2 weeks to avoid withdrawal symptoms and rebound worsening of psychotic or mood symptoms 1, 2.
For patients on 4 mg daily: reduce to 3 mg for 1-2 weeks, then 2 mg for 1-2 weeks, then 1 mg for 1-2 weeks before complete discontinuation 2, 3.
For patients on 2 mg daily: reduce to 1 mg for 1-2 weeks, then 0.5 mg for 1-2 weeks before stopping 2, 3.
Slower tapers extending 4-8 weeks may be necessary for patients with history of rapid relapse, severe episodes, or multiple hospitalizations 1.
Critical Monitoring Plan
Schedule weekly follow-up visits during the taper and for at least 2-3 months after the final dose, as this represents the highest risk period for relapse 1.
Monitor for early warning signs including sleep disturbance, increased anxiety, mood changes, emerging psychotic symptoms, or behavioral changes at each visit 1.
Assess for discontinuation symptoms such as insomnia, agitation, akathisia, or mood disturbances that may emerge during tapering 2, 3.
Extended monitoring may be required as symptom recurrence can occur weeks to months after the last dose, particularly for mood and psychotic disorders 1.
Managing Symptom Recurrence
If withdrawal symptoms or psychiatric destabilization occur during taper, immediately return to the previous stable dose and slow the reduction schedule further 1, 3.
If symptoms return after complete discontinuation, restart brexpiprazole at the previously effective dose and reconsider the appropriateness of discontinuation 1.
Special Considerations for Brexpiprazole
Brexpiprazole's pharmacological profile as a partial D2 agonist with lower intrinsic activity than aripiprazole suggests potentially lower risk of severe withdrawal symptoms, though systematic discontinuation data are limited 4, 5.
The drug's relatively favorable tolerability profile (low akathisia rates, minimal metabolic effects, moderate weight gain) means discontinuation is less likely to be driven by intolerable side effects compared to other antipsychotics 4, 6, 5.
Common Pitfalls to Avoid
Never discontinue brexpiprazole abruptly unless a medical emergency requires it, as this dramatically increases risk of symptom recurrence 1, 2.
Do not attempt discontinuation during periods of stress or environmental instability, as these factors increase relapse risk 1.
Avoid discontinuing in inpatient or partial hospital settings with short lengths of stay, as symptom recurrence may occur after discharge when monitoring is reduced 1.
Do not assume that absence of symptoms during the taper means discontinuation is safe—the greatest relapse risk occurs in the 8-12 weeks after stopping medication 1.
When Discontinuation May Not Be Appropriate
Patients with multiple severe episodes or treatment-resistant illness may require indefinite maintenance therapy, as withdrawal dramatically increases relapse risk 1, 2.
For schizophrenia maintenance, brexpiprazole significantly delayed time to relapse (13.5% vs 38.5% for placebo), suggesting strong protective effects that are lost upon discontinuation 6.