What are the extrapyramidal symptoms (EPS) associated with brexpiprazole (Rexulti)?

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Last updated: March 19, 2025View editorial policy

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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) include:

  • Akathisia
  • Dystonia (characterized by spasm of the neck muscles, tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue) Other EPS-related adverse reactions (excluding akathisia) may also occur, with an incidence of 6% in adjunctive MDD studies and 5% in schizophrenia studies 1.

From the Research

Brexpiprazole is associated with a low risk of extrapyramidal symptoms (EPS), with a significant decrease in EPS observed in patients switched to brexpiprazole from other antipsychotics, as demonstrated by a decrease in the Drug-Induced Extrapyramidal Symptoms Scale total score 2. The risk of EPS with brexpiprazole is dose-dependent, with higher doses carrying greater risk than lower doses. Some key points to consider when evaluating the risk of EPS with brexpiprazole include:

  • The medication's pharmacological profile, which includes partial agonism at D2 receptors rather than full blockade, allowing for adequate antipsychotic efficacy while minimizing movement disorders 3
  • The results of studies demonstrating the efficacy and safety of brexpiprazole in patients with schizophrenia, including those with severe symptoms 4
  • The importance of monitoring patients for EPS symptoms, including akathisia, parkinsonism, and dystonia, during treatment initiation and dose adjustments
  • The potential management options for EPS, including dose reduction, switching to an antipsychotic with even lower EPS risk, or adding an anticholinergic medication [@Example@] Overall, brexpiprazole appears to be a useful treatment option for patients with schizophrenia, with a relatively low risk of EPS compared to other antipsychotics.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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