Which statement about extrapyramidal symptoms is true?

Which statement about extrapyramidal symptoms is true?

• A. First-generation antipsychotics have a higher risk of EPS than second-generation.
• B. Second-generation antipsychotics have higher EPS risk than first-generation.
• C. EPS only occur at high doses.
• D. EPS are unrelated to antipsychotic class.

Answer: (A)

Extrapyramidal symptoms arise mainly from strong blockade of dopamine D2 receptors in the nigrostriatal pathway. Typical (first-generation) antipsychotics produce broad and robust D2 blockade in this pathway, leading to a higher likelihood of EPS. In contrast, atypical (second-generation) antipsychotics typically cause less D2 blockade in the striatum and also antagonize 5-HT2A receptors, which helps maintain dopamine activity in the motor circuits and reduces the risk of EPS. Because of this pharmacologic profile, the overall risk of EPS is lower with second-generation agents, though EPS can still occur at higher doses or with certain drugs within the class. So the statement is correct because it reflects the general class effect: first-generation antipsychotics carry a higher risk of EPS compared with second-generation antipsychotics. It’s also worth noting that EPS can occur at therapeutic doses for sensitive individuals or with potent agents, and some second-generation drugs (at high doses) can still cause EPS, but the baseline risk is lower with the atypicals.

Extrapyramidal symptoms arise mainly from strong blockade of dopamine D2 receptors in the nigrostriatal pathway. Typical (first-generation) antipsychotics produce broad and robust D2 blockade in this pathway, leading to a higher likelihood of EPS. In contrast, atypical (second-generation) antipsychotics typically cause less D2 blockade in the striatum and also antagonize 5-HT2A receptors, which helps maintain dopamine activity in the motor circuits and reduces the risk of EPS. Because of this pharmacologic profile, the overall risk of EPS is lower with second-generation agents, though EPS can still occur at higher doses or with certain drugs within the class.

So the statement is correct because it reflects the general class effect: first-generation antipsychotics carry a higher risk of EPS compared with second-generation antipsychotics. It’s also worth noting that EPS can occur at therapeutic doses for sensitive individuals or with potent agents, and some second-generation drugs (at high doses) can still cause EPS, but the baseline risk is lower with the atypicals.