Optimal Management of Schizophrenia on Rexulti (Brexpiprazole)

Pharmacological Management Algorithm

The American Psychiatric Association strongly recommends that patients whose symptoms have improved with an antipsychotic continue treatment with that same medication, in this case, brexpiprazole, at the dose that achieved symptom control (recommended range 2-4 mg/day) 1, 2
The American Psychiatric Association recommends monitoring 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 2, 3
Maintain brexpiprazole indefinitely for most patients, as 70% of individuals with schizophrenia require long-term or lifetime medication to control symptoms 4

If akathisia develops, lower the brexpiprazole dose, switch to another antipsychotic, add a benzodiazepine, or add a beta-blocker, as recommended by the American Psychiatric Association 1, 2
If parkinsonism develops, lower the dose, switch medications, or add an anticholinergic agent, as recommended by the American Psychiatric Association 1, 2
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

The American Psychiatric Association recommends cognitive-behavioral therapy for psychosis (CBTp) to address persistent symptoms and improve functioning 1, 2
The American Psychiatric Association recommends psychoeducation about the illness, medications, and warning signs of relapse 1, 2
The American Psychiatric Association recommends supported employment services to facilitate return to work or vocational functioning 1, 2
The American Psychiatric Association recommends coordinated specialty care program if this is a first episode of psychosis 1, 2
The American Psychiatric Association recommends assertive community treatment if there is a history of poor engagement with services, frequent relapse, homelessness, or legal difficulties 1, 2

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, as stated by the American Psychiatric Association and supported by evidence from Drugs 4, 3
Implement psychosocial interventions listed above, as these are the primary evidence-based treatments for negative symptoms and functional impairment, as recommended by the American Psychiatric Association 1, 2

Switch to clozapine if suicide risk remains substantial despite brexpiprazole treatment, as clozapine is specifically recommended for reducing suicide attempts, as recommended by the American Psychiatric Association 1, 2
Consider clozapine if aggressive behavior remains substantial despite other treatments, as recommended by the American Psychiatric Association 1, 2

Do not start antipsychotics for personality traits or prodromal symptoms alone without at least one week of psychotic symptoms causing distress or functional impairment, as recommended by Praxis Medical Insights 5
Do not mistake sedation or extrapyramidal symptoms for primary negative symptoms—these require dose reduction or medication switch, not dose increase, as recommended by the American Psychiatric Association and Praxis Medical Insights 1, 3