Optimal Management of Schizophrenia on Rexulti (Brexpiprazole)
If a patient with schizophrenia is currently on Rexulti and responding well, continue the same medication at the effective dose (2-4 mg/day) with ongoing monitoring for effectiveness and side effects, while simultaneously implementing evidence-based psychosocial interventions. 1, 2
Pharmacological Management Algorithm
If Patient is Responding to Rexulti
Continue current brexpiprazole therapy at the dose that achieved symptom control (recommended range 2-4 mg/day), as the APA strongly recommends that patients whose symptoms have improved with an antipsychotic continue treatment with that same medication 1
Monitor for effectiveness by tracking positive symptoms (hallucinations, delusions) using quantitative measures like the PANSS scale at regular intervals 1, 2
Consider long-acting injectable formulation if adherence becomes uncertain or if the patient prefers this route, as this supports consistent medication delivery 1, 3
Maintain indefinitely for most patients, as 70% of individuals with schizophrenia require long-term or lifetime medication to control symptoms 1
If Patient is Not Responding Adequately to Rexulti
After 4-6 weeks at therapeutic dose without adequate response, switch to an alternative antipsychotic with a different pharmacodynamic profile rather than increasing the brexpiprazole dose 4, 2
After two failed adequate antipsychotic trials (including the brexpiprazole trial), switch to clozapine, as 34% of patients are treatment-resistant to non-clozapine agents and clozapine is the only evidence-based treatment for treatment-resistant schizophrenia 1, 5
Avoid antipsychotic polypharmacy unless clozapine has failed, as adding additional antipsychotics increases side effect burden without established benefit 1, 3
Critical Side Effect Monitoring
Metabolic Monitoring
Obtain fasting glucose and lipid panel before or soon after initiation, then monitor periodically during long-term treatment 2
In long-term studies, 10% of patients with normal or borderline fasting glucose experienced shifts to high fasting glucose, and approximately 10% of patients gained ≥7% body weight 2, 6
Weight gain with brexpiprazole is moderate compared to other antipsychotics, with an NNH of 17 for ≥7% weight gain in short-term studies 6, 7
Movement Disorder Monitoring
Assess for akathisia at each visit, though rates are low (5.5% vs 4.6% placebo, NNH=112) 6, 7
If akathisia develops: lower the brexpiprazole dose, switch to another antipsychotic, add a benzodiazepine, or add a beta-blocker 1
If parkinsonism develops: lower the dose, switch medications, or add an anticholinergic agent 1
Monitor for tardive dyskinesia periodically, as risk increases with duration of treatment; if moderate to severe tardive dyskinesia develops, treat with a VMAT2 inhibitor 1, 2
Cardiovascular Monitoring
- Brexpiprazole shows no clinically relevant effects on QTc interval, making it safer than some alternatives in patients with cardiac concerns 6, 7
Mandatory Psychosocial Interventions
Do not rely on medication alone—the following psychosocial interventions have strong evidence and must be implemented concurrently:
Strongly Recommended (Level 1B Evidence)
Cognitive-behavioral therapy for psychosis (CBTp) to address persistent symptoms and improve functioning 1
Psychoeducation about the illness, medications, and warning signs of relapse 1
Supported employment services to facilitate return to work or vocational functioning 1
Coordinated specialty care program if this is a first episode of psychosis 1
Assertive community treatment if there is a history of poor engagement with services, frequent relapse, homelessness, or legal difficulties 1
Additional Interventions to Consider
Family interventions if the patient has ongoing family contact 1
Cognitive remediation to address cognitive deficits 1
Social skills training if enhanced social functioning is a treatment goal 1
Addressing Negative Symptoms and Motivation
Critical pitfall: Do not increase brexpiprazole dose or add additional antipsychotics to treat amotivation or negative symptoms, as antipsychotics effectively reduce positive symptoms but do not markedly improve negative symptoms or motivational deficits 1, 3
First, rule out medication-induced causes: If parkinsonism, akathisia, or sedation are present, these can mimic negative symptoms—lower the dose or switch medications rather than adding treatments 1, 3
Implement psychosocial interventions listed above, as these are the primary evidence-based treatments for negative symptoms and functional impairment 1
Maintain antipsychotic stability to prevent relapse, as this creates the foundation needed for psychosocial interventions to work 3
Special Populations and Situations
High Suicide Risk
- Switch to clozapine if suicide risk remains substantial despite brexpiprazole treatment, as clozapine is specifically recommended for reducing suicide attempts 1
High Aggression Risk
- Consider clozapine if aggressive behavior remains substantial despite other treatments 1
Maintenance Phase
Brexpiprazole demonstrated significant efficacy in relapse prevention, with only 13.5% relapse rate vs 38.5% for placebo (NNT=4) in a 52-week maintenance study 2, 6, 7
Continue at the dose that achieved stabilization (1-4 mg/day range in maintenance studies) 2
Common Pitfalls to Avoid
Do not start antipsychotics for personality traits or prodromal symptoms alone without at least one week of psychotic symptoms causing distress or functional impairment 4
Do not mistake sedation or extrapyramidal symptoms for primary negative symptoms—these require dose reduction or medication switch, not dose increase 1, 3
Do not delay clozapine in treatment-resistant patients due to fear of side effects—for patients with resistant symptoms, the benefits outweigh the risks, and patients have more favorable opinions of clozapine than physicians expect 5
Do not use brexpiprazole in elderly patients with dementia-related psychosis, as it carries a boxed warning for increased mortality in this population 2