Which class of antipsychotics is most associated with extrapyramidal symptoms (EPS)?

• A. SSRIs
• B. SNRIs
• C. Atypical antipsychotics
• D. Typical antipsychotics

Answer: (D)

Extrapyramidal symptoms arise when dopamine in the nigrostriatal motor pathways is strongly blocked. First-generation (typical) antipsychotics produce robust D2 receptor blockade in this pathway, which directly leads to EPS such as dystonia, parkinsonism, akathisia, and, with long-term use, tardive dyskinesia. The risk increases with higher potency and dose, so these drugs are the most associated with EPS.

Second-generation (atypical) antipsychotics also block dopamine but have additional serotonin receptor effects, particularly 5-HT2A antagonism, which tends to lessen EPS risk. They can still cause EPS in some cases, but far less commonly than typical antipsychotics.

SSRIs and SNRIs are antidepressants and are not primarily linked to extrapyramidal symptoms in the same way; their movement disorders, if they occur, aren’t a defining feature.

So, the class most associated with extrapyramidal symptoms is the typical antipsychotics.