What is the difference between Abilify (aripiprazole) and Rexulti (brexpiprazole)?

Differences Between Abilify (Aripiprazole) and Rexulti (Brexpiprazole)

Rexulti (brexpiprazole) has less intrinsic activity at D2 receptors and higher potency at 5-HT2A, 5-HT1A, and α1B receptors compared to Abilify (aripiprazole), resulting in a potentially more tolerable side effect profile, particularly regarding akathisia.

Pharmacological Differences

Mechanism of Action

• Both medications: Dopamine D2 receptor partial agonists (also called serotonin-dopamine activity modulators) 1, 2
• Key difference: Brexpiprazole has less intrinsic activity at D2 receptors and higher potency at 5-HT2A, 5-HT1A, and α1B receptors compared to aripiprazole 3

Receptor Profile

• Aripiprazole: Strong affinity for dopamine receptors, intermediate affinity for serotonin, adrenergic and histamine receptors 4
• Brexpiprazole: Similar receptor profile but with different binding affinities - higher potency at serotonin and adrenergic receptors 3

FDA-Approved Indications

Aripiprazole (Abilify)

• Schizophrenia
• Bipolar I disorder (manic and mixed episodes)
• Adjunctive treatment of major depressive disorder
• Irritability associated with autistic disorder
• Tourette's disorder 1

Brexpiprazole (Rexulti)

• Schizophrenia in adults
• Adjunctive therapy for major depressive disorder in adults 5

Side Effect Profiles

Akathisia and EPS

• Aripiprazole: Higher rates of akathisia and restlessness 4, 3
• Brexpiprazole: Lower rates of akathisia compared to aripiprazole 3

Weight Gain

• Aripiprazole: Generally lower risk of weight gain 4
• Brexpiprazole: More prominent weight gain than aripiprazole 3

Sedation

• Aripiprazole: Common side effect includes somnolence 4
• Brexpiprazole: Less sedation than aripiprazole, but still present 3

Metabolic Effects

• Aripiprazole: Well-tolerated regarding metabolic side effects 4
• Brexpiprazole: Similar metabolic profile, but may have slightly different risks 3

Dosing Considerations

Aripiprazole

• Available in multiple strengths: 2 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 30 mg 6
• Typical dosing range: 10-30 mg/day for schizophrenia and bipolar disorder 4

Brexpiprazole

• Target dosing: 2-4 mg in schizophrenia and 2 mg in depression augmentation 3
• Dose adjustments recommended in hepatic or renal dysfunction and/or in poor CYP2D6 metabolizers 3

Clinical Efficacy

Schizophrenia

• Brexpiprazole: Number needed to treat (NNT) vs placebo of 6-15 for response in acute schizophrenia treatment and 4 for maintenance 3
• Aripiprazole: Demonstrated efficacy in schizophrenia with maintenance of antipsychotic effects and relapse prevention 4

Depression

• Brexpiprazole: NNT is 12 for response and 17-31 for remission vs placebo in major depression 3
• Aripiprazole: Established efficacy as adjunctive treatment in major depressive disorder 1

Treatment Discontinuation Rates

• Brexpiprazole in schizophrenia: Lower discontinuation rates due to treatment-emergent adverse effects compared to placebo (7.1%-9.2% vs 14.7%) 3
• Brexpiprazole in depression: Higher discontinuation rates compared to placebo (1.3%-3.5% vs 0-1.4%) and appeared dose-dependent 3

Clinical Considerations

• Consider brexpiprazole for patients who experienced akathisia with aripiprazole but responded well to the medication class
• Consider aripiprazole for patients where weight gain is a significant concern
• Both medications require monitoring for metabolic parameters, though they generally have better metabolic profiles than many other antipsychotics
• Dose adjustments for both medications should be considered in patients with hepatic or renal impairment

Pitfalls and Caveats

• No direct head-to-head studies comparing the two medications are currently available 3
• Individual patient response may vary despite pharmacological differences
• Both medications may still cause akathisia, weight gain, and sedation, albeit at different rates
• Cost considerations may impact choice between these medications, as brexpiprazole is newer and likely more expensive