What is the most common typical antipsychotic associated with Extrapyramidal Symptoms (EPS)?

From the Guidelines

Haloperidol is the antipsychotic medication most likely to cause extrapyramidal symptoms (EPS). This first-generation (typical) antipsychotic has a high affinity for dopamine D2 receptors in the nigrostriatal pathway, which explains its strong association with EPS such as parkinsonism, akathisia, dystonia, and tardive dyskinesia, as noted in the study by 1. The risk of EPS with haloperidol increases with higher doses, but can occur even at lower doses in sensitive individuals. Other high-potency first-generation antipsychotics like fluphenazine and trifluoperazine also carry significant EPS risk.

Key Points to Consider

• When prescribing haloperidol, clinicians should start at the lowest effective dose, monitor closely for early signs of EPS, and consider prophylactic anticholinergic medication (such as benztropine 1-2mg daily) in high-risk patients, as suggested by 1.
• Second-generation (atypical) antipsychotics like quetiapine, clozapine, and olanzapine have significantly lower EPS risk due to their lower D2 receptor affinity and additional serotonergic activity, making them better options for patients with a history of or high risk for movement disorders.
• The study by 1 provides guidance on the management of delirium symptoms in adult patients, including the use of antipsychotic medications and their potential side effects.

Recommendations for Clinical Practice

• Clinicians should be aware of the potential for EPS when prescribing antipsychotic medications, particularly haloperidol, and take steps to minimize this risk.
• The use of anticholinergic medications to prevent EPS should be considered on a case-by-case basis, as recommended by 1.
• Patients with a history of or high risk for movement disorders should be considered for treatment with second-generation antipsychotics, which have a lower risk of EPS.

From the FDA Drug Label

Dose GroupsPlaceboRISPERIDONE 2 mgRISPERIDONE 6 mgRISPERIDONE 10 mgRISPERIDONE 16 mg Parkinsonism1.20.91.82.42.6 EPS Incidence13%17%21%21%35% Dose Groups RISPERIDONE 1 mgRISPERIDONE 4 mgRISPERIDONE 8 mgRISPERIDONE 12 mgRISPERIDONE 16 mg Parkinsonism 0.61.72.42.94.1 EPS Incidence 7%12%17%18%20% The most EPS antipsychotic is RISPERIDONE 16 mg, with a Parkinsonism score of 2.6 and an EPS incidence of 35% 2.

• Key points:
  • The incidence of EPS increases with the dose of RISPERIDONE.
  • The highest dose of RISPERIDONE (16 mg) has the highest incidence of EPS.
  • The EPS incidence for RISPERIDONE 16 mg is 35%.

From the Research

Most EPS Antipsychotic

• The most EPS (Extrapyramidal Symptoms) antipsychotic is likely to be haloperidol, as it has been consistently shown to have a higher incidence of EPS compared to other antipsychotics such as olanzapine 3, 4, 5, 6.
• Studies have found that haloperidol is associated with a higher risk of EPS, including parkinsonism, akathisia, and dyskinesia, compared to second-generation antipsychotics such as olanzapine and risperidone 4, 5, 6.
• A systematic review of 68 studies found that haloperidol may result in a large increase in extrapyramidal side effects compared to olanzapine, with a risk ratio of 3.38 (95% CI 2.28 to 5.02) 6.
• Another study found that haloperidol produced more EPS than other first-generation antipsychotics, including bromperidol, loxapine, and trifluoperazine 7.

Comparison with Other Antipsychotics

• Olanzapine has been shown to have a lower incidence of EPS compared to haloperidol, with a statistically significant difference in favor of olanzapine 3, 5, 6.
• Risperidone has also been found to have a lower incidence of EPS compared to haloperidol, although the difference was not always statistically significant 4, 5.
• Other first-generation antipsychotics, such as bromperidol, loxapine, and trifluoperazine, have been found to have a similar risk profile to haloperidol in terms of EPS 7.