What are alternatives to Rexulti (brexpiprazole) for treating psychiatric conditions?

Alternatives to Rexulti (Brexpiprazole) for Psychiatric Conditions

For patients requiring alternatives to Rexulti (brexpiprazole), several other antipsychotic medications can be effectively used depending on the specific psychiatric condition being treated, with risperidone, olanzapine, and quetiapine being first-line options for most conditions. 1

First-Generation (Typical) Antipsychotics

• Haloperidol is recommended as a first-line treatment for schizophrenia and bipolar mania, particularly when cost is a constraint 1
• Chlorpromazine is another first-line typical antipsychotic that can be used for psychotic disorders 1
• First-generation antipsychotics should be used cautiously in elderly patients due to higher risk of extrapyramidal symptoms (EPS) and tardive dyskinesia 1
• These medications are generally less expensive but carry higher risk of extrapyramidal side effects compared to second-generation options 1

Second-Generation (Atypical) Antipsychotics

For Schizophrenia:

• Risperidone (1.25-3.5 mg/day) is recommended as first-line for late-life schizophrenia 1, 2
• Quetiapine (100-300 mg/day) and olanzapine (7.5-15 mg/day) are high second-line options 1, 2
• Aripiprazole (15-30 mg/day) is another high second-line option with FDA approval for schizophrenia 3, 2
• Clozapine should be considered for treatment-resistant cases after failing two adequate antipsychotic trials 1

For Bipolar Disorder:

• Lithium, valproate, or carbamazepine should be offered to individuals with bipolar mania 1
• Second-generation antipsychotics may be used as alternatives if availability and cost are not constraints 1
• For maintenance treatment of bipolar disorder, lithium or valproate should be used for at least 2 years after the last episode 1

For Major Depressive Disorder:

• Antidepressant medications should be first-line for non-psychotic depression 1
• For adjunctive treatment in depression, aripiprazole has similar mechanism to brexpiprazole but with different side effect profile 4
• SSRIs (particularly fluoxetine) are preferred over tricyclic antidepressants when combined with mood stabilizers for bipolar depression 1

Special Populations Considerations

Elderly Patients:

• Lower doses should be used in elderly patients (e.g., risperidone 0.25-2 mg/day) 1
• For agitated dementia with delusions, risperidone (0.5-2.0 mg/day) is first-line, followed by quetiapine (50-150 mg/day) and olanzapine (5.0-7.5 mg/day) as high second-line options 2
• Avoid antipsychotics in dementia-related psychosis due to increased mortality risk unless benefits outweigh risks 3

Patients with Comorbidities:

• For patients with Parkinson's disease, quetiapine is first-line 2
• For patients with diabetes, dyslipidemia, or obesity, avoid clozapine, olanzapine, and low/mid-potency conventional antipsychotics 2
• For patients with QTc prolongation or heart failure, avoid clozapine, ziprasidone, and conventional antipsychotics 2

Comparative Side Effect Profiles

• Aripiprazole has higher rates of akathisia but less weight gain compared to brexpiprazole 4
• Olanzapine has higher risk of metabolic effects and weight gain 1
• Quetiapine is more sedating and may cause orthostatic hypotension 1
• Risperidone has moderate risk of extrapyramidal symptoms, especially at doses >6 mg/day 1
• Cariprazine has lower rates of sedation compared to brexpiprazole but similar mechanism as a partial D2 agonist 4

Acute Agitation Management

• For acute agitation, benzodiazepines (lorazepam or midazolam) or conventional antipsychotics (droperidol or haloperidol) are effective as monotherapy 1
• For agitated but cooperative patients, a combination of oral lorazepam and oral risperidone is recommended 1
• For rapid sedation, droperidol may be more effective than haloperidol 1

Treatment Duration Recommendations

• Antipsychotic treatment should be continued for at least 12 months after the beginning of remission in psychotic disorders 1
• For patients stable for several years on antipsychotic treatment, withdrawal may be considered after weighing risks of relapse and adverse effects 1
• For psychotic major depression, treatment should continue for approximately 6 months 2

Remember that medication selection should consider the specific psychiatric condition, patient's history of response, side effect profile, and cost considerations. Monitoring for adverse effects and regular reassessment of treatment efficacy is essential for all antipsychotic medications.