Final answer:
The most significant side effect associated with Clozaril (Clozapine) is agranulocytosis, which is a severe reduction in the white blood cell count, potentially leading to increased vulnerability to infections.
Step-by-step explanation:
The primary and most significant side effect associated with Clozaril (Clozapine) is D) Agranulocytosis, a severe reduction in white blood cell count. This condition can leave patients vulnerable to infections due to compromised immune function. Clozapine is known for its effectiveness in treating resistant schizophrenia, but its use is strictly regulated due to the risk of this serious side effect. Blood monitoring is required to promptly identify signs of agranulocytosis, and its potential occurrence is one of the major reasons why other treatments are considered before Clozaril. Aside from agranulocytosis, other side effects may occur, such as weight gain and metabolic issues, although they are not as significant as the risk of a severe reduction in white blood cell count.