Brexpiprazole (Rexulti) is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Brexpiprazole (trade name: Rexulti) is an atypical antipsychotic developed by Otsuka Pharmaceutical and Lundbeck[1]. It received FDA approval in 2023 for the treatment of agitation associated with Alzheimer's disease[2], making it the first antipsychotic approved specifically for this indication in nearly two decades.
Brexpiprazole belongs to a class of drugs called serotonin-dopamine activity modulators (SDAMs). It has a unique pharmacological profile with high affinity for multiple receptor subtypes, which may provide efficacy with a more favorable side effect profile compared to older antipsychotics.
Brexpiprazole's therapeutic effects in Alzheimer's disease agitation result from its activity at multiple neurotransmitter receptors:
| Receptor | Activity | Functional Effect |
|---|---|---|
| 5-HT1A | Partial agonist | Anxiolytic, antidepressant effects |
| 5-HT2A | Antagonist | Reduced psychosis, improved sleep |
| 5-HT2C | Antagonist | Weight neutrality |
| D2 | Partial agonist | Antipsychotic, antiagitation |
| D3 | Partial agonist | Cognitive effects |
| H1 | Antagonist | Sedation (mild) |
| α1 | Antagonist | Orthostatic hypotension (potential) |
Two pivotal Phase III trials (BREVIVE-1 and BREVIVE-2) evaluated brexpiprazole for agitation in Alzheimer's disease[3]:
| Study | Dose | Primary Endpoint | Result |
|---|---|---|---|
| BREVIVE-1 | 2 mg/day | CMAI change at week 12 | -20.6 vs -12.5 (placebo), p=0.0026 |
| BREVIVE-2 | 2 mg/day | CMAI change at week 12 | -18.6 vs -15.4 (placebo), p=0.0769 |
The BREVIVE-1 trial demonstrated statistically significant improvement in agitation symptoms as measured by the Cohen-Mansfield Agitation Inventory (CMAI).
Brexpiprazole is FDA-approved for:
Recommended dosing for AD agitation:
| Adverse Event | Frequency (Brexpiprazole) | Frequency (Placebo) |
|---|---|---|
| Headache | 6.7% | 5.8% |
| Dizziness | 5.2% | 2.5% |
| Somnolence | 5.2% | 2.1% |
| Constipation | 4.6% | 2.1% |
| Weight gain | 3.8% | 1.7% |
Brexpiprazole carries a boxed warning for:
Brexpiprazole should be considered for patients with:
| Parameter | Baseline | 4 weeks | 8 weeks | 12 weeks | Ongoing |
|---|---|---|---|---|---|
| Weight | ✓ | ✓ | ✓ | ✓ | Quarterly |
| Blood pressure | ✓ | ✓ | - | ✓ | Quarterly |
| Fasting glucose | ✓ | - | - | ✓ | Quarterly |
| Lipid panel | ✓ | - | - | ✓ | Quarterly |
| EPS assessment | ✓ | ✓ | ✓ | ✓ | As needed |
| Drug | Receptor Profile | EPS Risk | Sedation | Weight Gain | FDA AD Indication |
|---|---|---|---|---|---|
| Brexpiprazole | 5-HT1A/2A/D2 | Low | Low | Low | Yes (2023) |
| Risperidone | D2/5-HT2 | Moderate | Moderate | Moderate | No |
| Quetiapine | D2/5-HT2/H1 | Low | High | Moderate | No |
| Olanzapine | D2/5-HT2/H1 | Moderate | High | High | No |
| Aripiprazole | D2 partial | Low | Low | Low | No |
The study of Brexpiprazole (Rexulti) has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Citrome L. Brexpirazole for schizophrenia: a review of the efficacy and safety profile of this new "dopamine partial agonist-like" antipsychotic. International Journal of Clinical Practice. 2016;70(5):379-389. ↩︎
FDA. FDA Approves First Drug to Treat Agitation Symptoms Associated with Dementia Due to Alzheimer's Disease. May 2023. ↩︎
ClinicalTrials.gov. Brexpiprazole for the Treatment of Patients With Agitation Associated With Dementia of the Alzheimer's Type (NCT03620981). 2023. ↩︎