Is using Rexulti (brexpiprazole) instead of aripiprazole a problem?

Using Rexulti (Brexpiprazole) Instead of Aripiprazole

Substituting Rexulti (brexpiprazole) for aripiprazole is generally acceptable and may even be advantageous for some patients due to its potentially better side effect profile, though it has similar therapeutic effects.

Pharmacological Comparison

Brexpiprazole and aripiprazole belong to the same class of atypical antipsychotics and share similar mechanisms of action:

• Both are partial agonists at dopamine D2 and serotonin 5-HT1A receptors and antagonists at serotonin 5-HT2A receptors 1
• Brexpiprazole has less intrinsic activity at D2 receptors compared to aripiprazole 2
• Brexpiprazole has higher potency at 5-HT2A, 5-HT1A, and α1B receptors than aripiprazole 3

Potential Advantages of Brexpiprazole

The pharmacological differences translate to clinical advantages:

• Lower incidence of akathisia, insomnia, and agitation compared to aripiprazole 2
• Potentially lower risk of extrapyramidal symptoms due to lower intrinsic activity at D2 receptors 1
• Generally well-tolerated in clinical trials with treatment periods up to 52 weeks 4

Potential Disadvantages of Brexpiprazole

Some considerations when switching:

• More prominent weight gain compared to aripiprazole 3
• Different dosing requirements (target dosing is 2-4 mg for schizophrenia and 2 mg for depression augmentation) 3
• May require dose adjustments in patients with hepatic or renal dysfunction and/or in poor CYP2D6 metabolizers 3

Weight Considerations

According to clinical guidelines, both medications are classified similarly regarding weight effects:

• Aripiprazole is listed as "weight neutral/less weight gain" in pharmacotherapy guidelines 5
• While specific data on brexpiprazole's weight effects aren't listed in the provided guidelines, clinical studies suggest slightly more weight gain potential than aripiprazole but still less than many other antipsychotics 3

Clinical Applications

Both medications are approved for:

1. Schizophrenia
2. Adjunctive treatment in major depressive disorder

For specific conditions:

• In bipolar disorder, aripiprazole is FDA-approved for acute mania 5, while brexpiprazole doesn't have this specific indication
• Both can be used in treatment-resistant OCD as augmentation agents 5

Practical Considerations

When switching from aripiprazole to brexpiprazole:

• Ensure appropriate dosing conversion
• Monitor for changes in side effect profile
• Be aware that while both medications work similarly, individual response may vary
• Consider cost and insurance coverage differences

Common Pitfalls to Avoid

1. Assuming identical effects: Despite similar mechanisms, individual patient response may differ between the two medications
2. Overlooking dose adjustments: Brexpiprazole may require different dosing than aripiprazole
3. Ignoring metabolic monitoring: Continue monitoring weight and metabolic parameters after switching
4. Missing drug interactions: Both medications have interactions with CYP2D6 inhibitors, but the clinical significance may differ

In conclusion, substituting Rexulti for aripiprazole is generally acceptable and may provide benefits for patients experiencing activation-like side effects with aripiprazole, though careful monitoring for differences in efficacy and side effects is warranted.