How to treat Extrapyramidal Symptoms (EPS) caused by antipsychotic medication?

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From the Guidelines

Extrapyramidal symptoms (EPS) from antipsychotics should be treated promptly with anticholinergic medications such as benztropine (1-2 mg orally twice daily) or trihexyphenidyl (2-5 mg orally three times daily) as recommended by the American Psychiatric Association 1.

Treatment Options

  • For acute dystonic reactions, intramuscular benztropine 1-2 mg or diphenhydramine 25-50 mg provides rapid relief.
  • Propranolol 10-30 mg three times daily can help with akathisia if anticholinergics are ineffective, as suggested by the American Academy of Child and Adolescent Psychiatry 1.
  • Treatment duration varies; acute dystonia may require only short-term treatment (1-2 weeks), while persistent symptoms may need longer coverage.

Long-term Management

  • Dose reduction or switching to an atypical antipsychotic with lower EPS risk (quetiapine, clozapine, or aripiprazole) should be considered for long-term management, as these agents have a lower risk for extrapyramidal symptoms 1.
  • Tardive dyskinesia requires different management, potentially with VMAT2 inhibitors like valbenazine or deutetrabenazine.

Mechanism and Monitoring

  • EPS occurs because antipsychotics block dopamine receptors in the nigrostriatal pathway, creating an imbalance between dopamine and acetylcholine.
  • Anticholinergics restore this balance by reducing cholinergic activity.
  • Regular monitoring for EPS using standardized scales helps with early detection and intervention, as recommended by the American Psychiatric Association 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION ... Drug-Induced Extrapyramidal Disorders - In treating extrapyramidal disorders due to neuroleptic drugs (e.g., phenothiazines), the recommended dosage is 1 to 4 mg once or twice a day orally, or parenterally.

In acute dystonic reactions, 1 to 2 mL of the injection usually relieves the condition quickly After that, the tablets, 1 to 2 mg twice a day, usually prevents recurrence.

When extrapyramidal disorders develop soon after initiation of treatment with neuroleptic drugs (e.g., phenothiazines), they are likely to be transient. One to 2 mg of benztropine mesylate tablets two or three times a day usually provides relief within one or two days.

The treatment for Extrapyramidal Symptoms (EPS) caused by antipsychotic medication is benztropine mesylate, with a recommended dosage of 1 to 4 mg once or twice a day orally, or parenterally.

  • The dosage may be adjusted based on the patient's need, with some patients requiring more or less than the recommended amount.
  • In cases of acute dystonic reactions, an injection of 1 to 2 mL may be used to quickly relieve the condition, followed by 1 to 2 mg tablets twice a day to prevent recurrence.
  • For transient extrapyramidal disorders that develop soon after initiation of neuroleptic drugs, 1 to 2 mg of benztropine mesylate tablets two or three times a day may provide relief within one or two days 2.

From the Research

Treatment of Extrapyramidal Symptoms (EPS)

The treatment of EPS caused by antipsychotic medication involves several strategies, including:

  • Starting an antiparkinsonian agent immediately to provide relief to the patient if EPS occur 3
  • Using the lowest effective dosage of antipsychotic to minimize the risk of EPS 4
  • Treating the reactions with medications such as anticholinergic agents, beta-blockers, or benzodiazepines 4
  • Changing the antipsychotic to one with less potential for inducing EPS, such as atypical antipsychotics 4, 5
  • Discontinuing prophylactic antiparkinsonian treatment at least two weeks after its initiation, as long-term use is not therapeutically beneficial 3

Management of Specific EPS

The management of specific EPS includes:

  • Acute dystonias: treatment with anticholinergic medications or benzodiazepines 4
  • Pseudoparkinsonism: management by lowering the antipsychotic dosage or adding an anticholinergic agent or a mantadine; switching to a low-potency agent or an atypical antipsychotic may also help 4
  • Akathisia: treatment with lipophilic beta-blockers, especially propranolol and metoprolol, or anticholinergic agents, or benzodiazepines 4
  • Tardive dyskinesia: no specific treatment is mentioned in the studies, but it is noted that atypical antipsychotics may have less potential to induce EPS 3, 5

Prevention of EPS

Prevention of EPS involves:

  • Using atypical antipsychotics, which may have less potential to induce EPS 3, 5
  • Avoiding high doses of antipsychotic medication 3
  • Avoiding combinations of conventional and atypical antipsychotic drugs 3
  • Identifying high-risk patients and providing prophylactic antiparkinsonian therapy if necessary 3

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Management of acute extrapyramidal effects induced by antipsychotic drugs.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 1997

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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