Which adverse effect is commonly associated with second-generation antipsychotics, particularly olanzapine?

• A. Metabolic Syndrome
• B. Extrapyramidal Symptoms
• C. Hyperprolactinemia
• D. Insomnia

Answer: (A)

Second-generation antipsychotics, and olanzapine in particular, are often linked with metabolic effects that significantly impact long-term health. Olanzapine can cause substantial weight gain and disrupt glucose and lipid metabolism, leading to insulin resistance and dyslipidemia. These changes cluster together as metabolic syndrome, which includes central obesity, high triglycerides, low HDL cholesterol, and impaired glucose tolerance or diabetes. This tendency is driven by receptor effects such as antagonism of histamine H1 and serotonin 2C receptors, which increase appetite and alter energy balance, along with metabolic changes in insulin signaling. Among the options, this metabolic risk is the most characteristic and clinically important feature of olanzapine. Extrapyramidal symptoms are more associated with older antipsychotics and less with SGAs, hyperprolactinemia is more common with risperidone/paliperidone, and insomnia is not a defining adverse effect of olanzapine (though sedation can occur).