Rexulti (Brexpiprazole) vs. Abilify (Aripiprazole) for Augmenting Depression Treatment
Both Rexulti (brexpiprazole) and Abilify (aripiprazole) are atypical antipsychotics used as adjunctive treatments for major depressive disorder (MDD), particularly in patients who do not respond adequately to antidepressants alone. However, there are differences in efficacy, tolerability, and mechanism of action that may influence which one is more effective for a given patient.
1. Mechanism of Action: How Do They Work?
Both drugs modulate dopamine and serotonin systems but with slight differences in receptor activity.
|
Property |
Rexulti (Brexpiprazole) |
Abilify (Aripiprazole) |
|
Dopamine D2 Partial Agonist |
Lower intrinsic activity (more stabilizing) |
Higher intrinsic activity (more activating) |
|
Serotonin 5-HT1A Partial Agonist |
Yes (similar to Abilify) |
Yes |
|
Serotonin 5-HT2A Antagonist |
Stronger than Abilify |
Weaker than Rexulti |
|
Serotonin 5-HT2C Antagonist |
Yes (may improve mood and reduce weight gain) |
Weak or negligible |
|
Noradrenergic Activity |
Minimal |
Minimal |
Key Difference:
Rexulti is considered more “gentle” and stabilizing due to its lower intrinsic dopamine activity, which may lead to fewer activating side effects like restlessness and akathisia.
Abilify has stronger dopamine modulation, which may be more energizing but also more likely to cause restlessness or agitation.
2. Effectiveness in Augmenting Depression Treatment
Both drugs have been FDA-approved as adjuncts to antidepressants for treatment-resistant depression (TRD), but clinical trials and patient experiences suggest some differences.
Clinical Studies & Efficacy:
Rexulti (Brexpiprazole)
Clinical trials show statistically significant improvement in depressive symptoms when added to SSRIs or SNRIs.
More gradual effect with fewer side effects than Abilify.
Better for patients with anxiety and emotional dysregulation.
Abilify (Aripiprazole)
Effective for many patients as an adjunct but tends to be more activating.
Higher rates of akathisia (inner restlessness), which may be distressing for some.
More likely to cause emotional blunting due to stronger dopamine modulation.
Which is More Effective?
Rexulti may be more tolerable and slightly more effective for reducing depressive symptoms in some patients, according to clinical trials and real-world data.
Abilify may work faster and provide more activation, but this can be problematic for anxious or agitated patients.
Caveat: Effectiveness varies by individual, and some may respond better to one than the other.
3. Side Effects: Which is More Tolerable?
|
Side Effect |
Rexulti (Brexpiprazole) |
Abilify (Aripiprazole) |
|
Weight Gain |
Mild-Moderate (Less than other antipsychotics) |
Mild-Moderate (Similar risk) |
|
Akathisia (Restlessness) |
Lower risk (9%) |
Higher risk (20%+) |
|
Sedation / Fatigue |
Moderate |
Moderate |
|
Emotional Blunting |
Less common |
More common |
|
Blood Sugar/Diabetes Risk |
Some risk |
Some risk |
|
Prolactin Elevation |
Rare |
Rare |
Key Takeaways on Side Effects:
Rexulti has a lower risk of akathisia (restlessness), making it better tolerated for many patients.
Abilify can be more activating, which may be good for low-energy depression but bad for anxious patients.
Both cause some weight gain, but less than older atypical antipsychotics (e.g., olanzapine).
4. Dosage & Cost Considerations
|
Factor |
Rexulti (Brexpiprazole) |
Abilify (Aripiprazole) |
|
Typical Adjunct Dose |
13 mg/day |
25 mg/day |
|
Onset of Action |
Slower (24 weeks for full effect) |
Faster (12 weeks for noticeable effect) |
|
Half-Life |
~91 hours |
~75 hours |
|
Cost |
More expensive |
Less expensive (generic available) |
Key Considerations:
Rexulti is newer and more expensive, but may have fewer side effects.
Abilify is available in generic form, making it more affordable.
Abilify works faster, while Rexulti builds gradually.
5. Which One to Choose?
Choose Rexulti if:
You have anxiety alongside depression (less activating).
You are sensitive to akathisia or emotional blunting.
You prefer a gentler, more tolerable medication.
Choose Abilify if:
You need a faster-acting adjunct.
You have low-energy depression and need more activation.
You are looking for a more affordable option.
When to Avoid Both?
If you have bipolar disorder (unless prescribed carefully).
If you have severe metabolic syndrome or uncontrolled diabetes.
If you have severe akathisia or history of agitation with antipsychotics.
6. Conclusion: Is Rexulti More Effective?
Rexulti is generally considered better tolerated than Abilify for adjunct depression treatment due to:
Lower risk of akathisia
More gradual mood stabilization
Better efficacy in patients with anxiety or emotional sensitivity
However, Abilify remains a strong option, especially for patients who need a more activating medication and a more cost-effective choice.
Overall, Rexulti may be slightly more effective for a broader range of patients, but individual responses vary. If one does not work, switching to the other is a reasonable strategy.
