What is the management of Extrapyramidal Symptoms (EPS)?

From the Guidelines

The management of extrapyramidal symptoms (EPS) involves prompt recognition and appropriate interventions, with first-line treatment including reducing the dose or discontinuing the causative medication, typically antipsychotics, as supported by the most recent evidence 1. The goal of treatment is to alleviate symptoms while minimizing the risk of adverse effects.

• For acute dystonic reactions, anticholinergic medications such as benztropine (1-2 mg IV/IM/PO) or diphenhydramine (25-50 mg IV/IM/PO) provide rapid relief, as noted in previous studies 1.
• For ongoing EPS, oral anticholinergics like benztropine (1-2 mg twice daily) or trihexyphenidyl (2-5 mg three times daily) are effective, although their use should be balanced against potential side effects including cognitive impairment, urinary retention, and constipation 1.
• Parkinsonism symptoms may respond to amantadine (100 mg twice daily) or beta-blockers like propranolol (10-30 mg three times daily) for akathisia, with the choice of medication depending on the specific clinical context and patient factors 1.
• Tardive dyskinesia requires different management, potentially with VMAT2 inhibitors like valbenazine or deutetrabenazine, which have been shown to be effective in reducing symptoms of tardive dyskinesia 1.
• Switching to an atypical antipsychotic with lower EPS risk (quetiapine, clozapine) is often beneficial, as these medications have a lower propensity to cause EPS compared to typical antipsychotics, as discussed in the literature 1. These medications work by restoring neurotransmitter balance, particularly in the dopaminergic and cholinergic systems that become dysregulated with dopamine blockade.
• Prophylactic anticholinergics may be considered for high-risk patients, though they should be used cautiously due to potential side effects, and their use should be guided by the most recent and highest quality evidence available 1.

From the FDA Drug Label

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. Dosage must be individualized according to the need of the patient. 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 management of Extrapyramidal Symptoms (EPS) includes:

• Dosage: 1 to 4 mg of benztropine mesylate once or twice a day orally, or parenterally, individualized according to the need of the patient 2
• Acute dystonic reactions: 1 to 2 mL of the injection to relieve the condition, followed by 1 to 2 mg tablets twice a day to prevent recurrence
• Transient EPS: 1 to 2 mg of benztropine mesylate tablets two or three times a day for 1 to 2 days, with reassessment after 1 to 2 weeks to determine continued need for the drug 2

From the Research

Management of Extrapyramidal Symptoms (EPS)

The management of EPS induced by antipsychotic drugs involves several strategies, including:

• Treating acute dystonias with anticholinergic medications or benzodiazepines 3
• Managing pseudoparkinsonism 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 3
• Using lipophilic beta-blockers, especially propranolol and metoprolol, to treat akathisia 3
• Starting an antiparkinsonian agent immediately to provide relief to the patient if EPS occur 4
• Discontinuing antiparkinsonian treatment at least two weeks after its initiation, as long-term use is not therapeutically beneficial 4

Treatment Options

Treatment options for EPS include:

• Changing the neuroleptic to an alternative one, such as switching to a low-potency or an atypical antipsychotic 5
• Lowering the dosage or discontinuing the neuroleptic 5
• Adding a drug effective in treating EPS, such as an anticholinergic agent or a beta-blocker 5
• Using dantrolene and/or bromocriptine for the treatment of neuroleptic malignant syndrome (NMS) 5

Prevention and Prophylaxis

Prevention and prophylaxis of EPS involve:

• Using the lowest effective dosage of antipsychotic 3
• Treating the reactions with medications 3
• Changing the antipsychotic to one with less potential for inducing EPS 3
• Prophylactic antiparkinsonian therapy in high-risk patients, but routine prophylaxis with antiparkinsonian agents is harmful 4

Assessment and Rating Scales

Assessment and rating scales for EPS include:

• The Extrapyramidal Symptom Rating Scale (ESRS), which assesses four types of drug-induced movement disorders (DIMD): Parkinsonism, akathisia, dystonia, and tardive dyskinesia (TD) 6
• Factor analysis of the ESRS, which provided six factors: hypokinetic Parkinsonism, orofacial dyskinesia, trunk/limb dyskinesia, akathisia, tremor, and tardive dystonia 6