From the FDA Drug Label
The incidence of reported extrapyramidal symptoms (EPS)-related adverse reactions, excluding akathisia, was 6% for brexpiprazole plus ADT-treated patients versus 3% for placebo plus ADT-treated patients The incidence of akathisia events for brexpiprazole plus ADT-treated patients was 9% versus 2% for placebo plus ADT-treated patients. The incidence of reported EPS-related adverse reactions, excluding akathisia, was 5% for brexpiprazole-treated patients versus 4% for placebo-treated patients. The incidence of akathisia events for brexpiprazole-treated patients was 6% versus 5% for placebo-treated patients Dystonic symptoms include spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue
The extrapyramidal symptoms (EPS) associated with brexpiprazole (Rexulti) treatment include:
- Akathisia
- Dystonia, which may manifest as:
- Spasm of the neck muscles
- Tightness of the throat
- Swallowing difficulty
- Difficulty breathing
- Protrusion of the tongue Other EPS-related adverse reactions may occur, but the specific types are not detailed in the label 1.
From the Research
Brexpiprazole is associated with a relatively low risk of extrapyramidal symptoms (EPS), with a significant decrease in EPS observed when switching to brexpiprazole from other antipsychotics, as demonstrated by a decrease in the Drug-Induced Extrapyramidal Symptoms Scale total score 2. The incidence of EPS with brexpiprazole is approximately 5-7%, which is lower than first-generation antipsychotics and some second-generation options like risperidone. This favorable profile is due to brexpiprazole's partial agonism at D2 receptors rather than full antagonism, resulting in less dopamine blockade in the nigrostriatal pathway. When EPS does occur, it typically manifests as:
- Akathisia
- Parkinsonism symptoms The risk increases with higher doses, particularly above 3mg daily. To manage EPS if it develops, the following strategies can be considered:
- Dose reduction
- Adding anticholinergic medications like benztropine (1-2mg twice daily) or propranolol (10-20mg three times daily) specifically for akathisia Patients should be monitored for EPS using standardized scales like the AIMS or SAS, especially during the first few weeks of treatment and after dose increases. Elderly patients and those with pre-existing movement disorders are at higher risk and may require closer monitoring or lower starting doses 2. It is essential to note that switching to brexpiprazole can improve EPS, high prolactin levels, and metabolic side effects without elevating plasma homovanillic acid levels, as shown in a study published in 2021 2. In contrast to other antipsychotics, brexpiprazole's unique mechanism of action may contribute to its lower risk of EPS, making it a valuable treatment option for patients with schizophrenia or schizoaffective disorder 2.