What is a cost-effective alternative to Rexulti (brexpiprazole) for treating schizophrenia or major depressive disorder in adults?

Cost-Effective Alternatives to Rexulti (Brexpiprazole)

For schizophrenia, generic aripiprazole is the most cost-effective alternative to Rexulti, offering similar efficacy with a well-established safety profile at substantially lower cost. For major depressive disorder, generic second-generation antidepressants (particularly sertraline, citalopram, or escitalopram) combined with cognitive behavioral therapy represent the most cost-effective approach.

For Schizophrenia

First-Line Alternative: Generic Aripiprazole

• Aripiprazole shares the same mechanism of action as brexpiprazole (both are dopamine D2 and serotonin 5-HT1A partial agonists with 5-HT2A antagonism), making it pharmacologically the closest alternative 1, 2.

• Aripiprazole demonstrates effective symptomatic control in acute schizophrenia with favorable tolerability, particularly regarding extrapyramidal symptoms and metabolic effects 1.

• Cost-effectiveness analyses show aripiprazole provides superior value compared to other atypical antipsychotics, with lower incidence of weight gain and metabolic syndrome than olanzapine while maintaining comparable efficacy 1.

Additional Cost-Effective Options

• Generic risperidone represents the least costly atypical antipsychotic option for outpatient chronic schizophrenia treatment 3, 4.

• Generic olanzapine shows the highest remission rates (64.1% of patients) and is cost-effective when considering the efficient frontier of treatment options, though it carries higher metabolic risks 3.

• Among non-dominated treatment strategies for chronic schizophrenia, the cost-effective choices are haloperidol, haloperidol decanoate, olanzapine, and risperidone 3.

Clinical Decision Algorithm

1. Start with generic aripiprazole (10-30 mg daily) as the closest pharmacologic match to brexpiprazole with established cost-effectiveness 1.

2. If metabolic concerns are paramount, consider generic ziprasidone or lurasidone (though lurasidone has an ICER of $25,884 per hospitalization avoided versus risperidone) 4.

3. If cost is the primary driver, generic risperidone (2-6 mg daily) offers the lowest acquisition costs, though monitor for extrapyramidal symptoms and metabolic effects 3, 4.

4. If maximizing remission rates is critical, generic olanzapine (10-20 mg daily) shows highest effectiveness but requires careful metabolic monitoring 3.

For Major Depressive Disorder (Adjunctive Treatment)

First-Line Approach

• The American College of Physicians recommends either cognitive behavioral therapy or second-generation antidepressants as first-line treatment for major depressive disorder, with selection based on treatment effects, adverse profiles, cost, accessibility, and patient preferences 5, 6, 7.

• Generic second-generation antidepressants are substantially more cost-effective than atypical antipsychotics for depression treatment 5.

Specific Medication Recommendations

• Preferred cost-effective agents include: sertraline ($7-10/month for 50-200 mg), citalopram ($4/month for 20-40 mg), escitalopram ($10/month for 10-20 mg), bupropion SR ($14-33/month for 100-400 mg), mirtazapine ($5-20/month for 15-45 mg), and venlafaxine ($14-30/month for 37.5-225 mg) 5.

• These agents have favorable adverse effect profiles and established efficacy comparable to other antidepressants 5, 7.

When Augmentation is Needed

• If a patient has failed adequate trials of antidepressants and psychotherapy, generic aripiprazole (2-15 mg daily) is the most cost-effective atypical antipsychotic for augmentation, given its similar mechanism to brexpiprazole but at substantially lower cost 1.

• Brexpiprazole specifically shows efficacy in MDD patients with anxiety symptoms as adjunctive therapy, so aripiprazole would be the logical cost-effective substitute 2.

Important Caveats

• Cost-effectiveness data for antipsychotics shows inconsistent conclusions across studies due to methodological heterogeneity, different patient populations, and varying time horizons 5.

• Inpatient hospitalization costs represent the major cost driver (accounting for 62.1% of costs for atypical antipsychotics), making prevention of relapse and hospitalization the key economic outcome 3.

• Generic medications listed have acquisition costs 90-95% lower than brand-name alternatives while maintaining equivalent efficacy 5.

• Treatment duration should continue for 4-12 months after first episode, with longer duration for recurrent illness 5.