Which short-term effect is listed under glucose intolerance risk for clozapine and olanzapine?

• A. Galactorrhea
• B. Hypertension
• C. Weight gain
• D. Rash

Answer: (A)

Glucose intolerance risk with clozapine and olanzapine is driven by their metabolic effects. These drugs commonly cause weight gain early in treatment, and that increase in weight tends to worsen insulin sensitivity, leading to impaired glucose tolerance or prediabetes. The mechanism isn’t about prolactin or blood pressure; it’s about how these medications raise appetite and caloric intake through activity at histamine and serotonin receptors in the brain, especially histamine H1 and 5-HT2C receptors, which accelerates weight gain and metabolic changes.

Galactorrhea, on the other hand, comes from increased prolactin due to dopamine D2 receptor blockade and is more characteristic of drugs with a stronger propensity to elevate prolactin, like some other antipsychotics. Clozapine and olanzapine have relatively low prolactin effects, so galactorrhea isn’t a typical short-term risk with them. Hypertension and rash aren’t specifically tied to the glucose intolerance risk that these agents pose. In practice, baseline metabolic screening and periodic monitoring of weight, fasting glucose, and lipids are important when using these medications.