What is the recommended treatment approach for acute psychosis using Rexulti (brexpiprazole)?

Rexulti (Brexpiprazole) for Acute Psychosis

Rexulti (brexpiprazole) is NOT recommended as a first-line treatment for acute psychosis and should not be used in the emergency management of acute psychotic agitation. 1, 2, 3

Why Brexpiprazole is Not Appropriate for Acute Psychosis

Lack of Immediate Efficacy

• Brexpiprazole requires 4-6 weeks of treatment before antipsychotic effects become apparent, with any immediate effects being due only to sedation rather than true antipsychotic action. 2
• This delayed onset makes it unsuitable for acute psychotic episodes requiring rapid symptom control. 2

No Intramuscular Formulation Available

• Brexpiprazole is only available in oral formulation, which is impractical for acutely agitated or uncooperative patients who often require parenteral administration. 4
• Current guidelines recommend intramuscular haloperidol (2-5 mg), olanzapine (10 mg), or lorazepam/midazolam for acute psychotic agitation requiring rapid control. 3

Recommended First-Line Treatments for Acute Psychosis Instead

For Cooperative Patients (Oral Route)

• Start with oral risperidone 2 mg plus lorazepam 2 mg, which is as effective as intramuscular haloperidol plus lorazepam and avoids injection-related complications. 3
• Alternative oral options include risperidone 2 mg/day or olanzapine 7.5-10 mg/day as monotherapy. 1, 2

For Agitated/Uncooperative Patients (Intramuscular Route)

• Use haloperidol 5 mg IM plus lorazepam 2 mg IM for more rapid sedation when immediate control is necessary. 5, 3
• Alternatively, haloperidol 2-5 mg IM or olanzapine 10 mg IM as monotherapy are effective options. 3
• For undifferentiated agitation where psychosis etiology is unclear, lorazepam or midazolam IM alone may be preferred to avoid antipsychotic side effects. 5, 3

When Brexpiprazole Might Be Considered

After Acute Stabilization Only

• Brexpiprazole may be considered as a maintenance treatment option only after acute symptoms have been controlled with first-line agents (typically after 4-6 weeks). 2, 6
• The recommended dose for schizophrenia maintenance is 2-4 mg/day, starting at 1 mg/day and titrating to 2 mg/day on days 5-7, then to 4 mg/day on day 8. 6, 7

Potential Advantages for Long-Term Use

• Brexpiprazole demonstrates lower propensity for extrapyramidal symptoms and akathisia compared to traditional antipsychotics (NNH of 112 for akathisia vs placebo). 6, 7
• It shows modest weight gain in short-term studies (NNH of 17 for ≥7% weight gain), though long-term data show more outliers. 7
• Minimal effects on prolactin and QTc interval make it favorable for patients with metabolic or cardiac concerns. 6, 7

Critical Pitfalls to Avoid

Do Not Use for Emergency Situations

• Never initiate brexpiprazole in the emergency department or for acute psychotic crises requiring immediate symptom control. 2, 3
• The 4-6 week delay before therapeutic effects contradicts the urgent need for symptom management in acute psychosis. 2

FDA Black Box Warnings Apply

• Increased mortality risk in elderly patients with dementia-related psychosis - brexpiprazole is not approved for this indication. 4
• Increased risk of suicidal thoughts and behaviors in patients under 24 years, especially within the first few months of treatment. 4

Avoid Premature Switching

• If considering brexpiprazole after initial stabilization, ensure adequate trials of first-line agents (at least 4-6 weeks each at therapeutic doses) before switching. 2
• When switching from a first-line agent, choose medications with different pharmacodynamic profiles to maximize treatment response. 2

Treatment Algorithm for Acute Psychosis

1. Immediate assessment: Rule out medical causes (CNS infections, traumatic brain injury, substance intoxication) before assuming primary psychiatric etiology. 2

2. Acute phase (Days 1-7): Use haloperidol 5 mg IM + lorazepam 2 mg IM for rapid control, or oral risperidone 2 mg + lorazepam 2 mg for cooperative patients. 5, 3

3. Early stabilization (Weeks 1-6): Continue risperidone 2 mg/day or olanzapine 7.5-10 mg/day, avoiding dose escalation before 14-21 days. 1, 2

4. Maintenance consideration (After 6+ weeks): Only after stabilization, consider brexpiprazole 2-4 mg/day if first-line agents cause intolerable side effects or inadequate response. 6, 7

5. Treatment-resistant cases: After failure of two adequate trials (4-6 weeks each), consider clozapine rather than brexpiprazole. 2