Which statement is true regarding the relationship between high-potency FGAs and NMS?

• A. NMS is more common with high-potency FGAs.
• B. NMS is more common with low-potency FGAs.
• C. NMS occurs equally with all FGAs.
• D. NMS only occurs with SGAs.

Answer: (A)

The main idea here is that neuroleptic malignant syndrome risk tracks with how strongly a drug blocks dopamine D2 receptors in the brain. High-potency first-generation antipsychotics bind D2 receptors very tightly and at lower doses, producing a stronger, more widespread blockade in areas that regulate movement and temperature. This substantial blockade disrupts dopaminergic signaling enough to precipitate NMS, making it more likely than with low-potency FGAs, which achieve less intense D2 blockade at typical doses. While any antipsychotic can rarely trigger NMS, the incidence is higher with drugs that cause potent D2 inhibition. It’s also worth remembering that NMS can occur with second-generation antipsychotics, though less commonly, since their D2 blockade tends to be less intense or has different kinetics.