What are the considerations for prescribing Rexulti (brexpiprazole) to a patient with a normal pressure hydrocephalus (NPH) shunt and a history of psychiatric conditions, such as schizophrenia or bipolar disorder?

Rexulti (Brexpiprazole) Use in Patients with NPH Shunt and Psychiatric Conditions

Brexpiprazole can be safely prescribed to patients with NPH shunts who have schizophrenia or bipolar disorder, as there are no known contraindications between antipsychotic medications and ventricular shunts, though careful monitoring for behavioral changes that might signal shunt malfunction is essential. 1, 2

Key Safety Considerations

No Direct Contraindication

• The FDA labeling for brexpiprazole does not list NPH shunts or any neurosurgical hardware as contraindications to treatment 1
• Antipsychotic medications, including brexpiprazole, are not metabolized or affected by the presence of ventricular shunts 1

Critical Monitoring Requirement

• Patients with NPH shunts who develop new or worsening psychotic symptoms may be experiencing shunt malfunction rather than psychiatric decompensation—this requires urgent neurosurgical evaluation before adjusting psychiatric medications 2
• One documented case showed psychosis that resolved with shunt placement, recurred with each shunt malfunction, and resolved again with shunt revision, demonstrating the temporal relationship between hydrocephalus and psychiatric symptoms 2
• NPH can present initially as psychosis years before classic triad symptoms (gait apraxia, dementia, urinary incontinence) develop 2

Standard Dosing and Titration

For Schizophrenia

• Start brexpiprazole 1 mg orally once daily on Days 1-4, increase to 2 mg daily on Days 5-7, then titrate to target dose of 2-4 mg daily based on response 1
• Maximum recommended dose is 4 mg daily for schizophrenia 1

For Bipolar Disorder (Adjunctive Treatment)

• Start at 0.5 mg or 1 mg orally once daily, titrate to 1 mg daily, then to target dose of 2 mg daily at weekly intervals 1
• Maximum recommended dose is 3 mg daily for bipolar disorder 1

Advantages of Brexpiprazole in This Population

Lower Risk Profile

• Brexpiprazole demonstrates relatively low incidence of activating adverse effects (akathisia, insomnia, agitation) compared to aripiprazole, which is clinically significant for patients who may already have behavioral symptoms from NPH 3, 4
• Lower propensity for extrapyramidal symptoms compared to other antipsychotics, reducing diagnostic confusion with gait disturbances from NPH 3, 4
• Moderate weight gain and metabolic changes that are not clinically significant in most patients 3

Specific Monitoring Protocol for NPH Shunt Patients

Distinguish Psychiatric vs. Neurological Deterioration

• If patient develops acute worsening of psychosis, confusion, or behavioral changes while on stable brexpiprazole dose, obtain urgent brain imaging to assess shunt function before attributing symptoms to psychiatric illness 2
• Monitor for classic NPH triad: gait apraxia, cognitive decline, and urinary incontinence, which may develop after psychotic symptoms 2

Standard Antipsychotic Monitoring

• Assess for akathisia—if present, lower brexpiprazole dose, add benzodiazepine, or add beta-blocker 5, 6
• Monitor for tardive dyskinesia periodically, as risk increases with treatment duration 1
• Check fasting glucose and metabolic parameters at baseline and periodically during long-term treatment 1

Common Pitfall to Avoid

Do not automatically increase brexpiprazole dose or add additional antipsychotics when a patient with an NPH shunt develops worsening psychosis—shunt malfunction must be ruled out first with neuroimaging, as treating presumed psychiatric decompensation with higher antipsychotic doses will not address the underlying hydrocephalus and delays necessary neurosurgical intervention 2