Which generation of antipsychotics is primarily associated with a lower risk of extrapyramidal symptoms?

The second generation of antipsychotics, often referred to as atypical antipsychotics, is primarily associated with a lower risk of extrapyramidal symptoms (EPS) compared to the first generation, which are known for their higher incidence of these side effects. Atypical antipsychotics, such as clozapine, risperidone, and olanzapine, have a different mechanism of action that notably includes antagonism at serotonin receptors in addition to dopamine receptors. This broader receptor profile helps mitigate the severity of motor side effects commonly associated with dopamine blockade, particularly in areas of the brain that regulate movement.

In contrast, first generation antipsychotics predominantly target dopamine D2 receptors, which makes them more prone to causing EPS including akathisia, dystonia, and tardive dyskinesia. Third generation antipsychotics, while having their own unique mechanisms, still do not demonstrate a significant improvement over the second generation regarding EPS risk, and thus the second generation is recognized as having a distinct advantage in this regard. Understanding the risk of EPS is crucial for treatment planning and patient management in psychiatric care.