Which class of antipsychotics is primarily associated with metabolic syndrome?

• A. FGAs
• B. SGAs
• C. Antipsychotics
• D. Antidepressants

Answer: (B)

Metabolic syndrome—characterized by weight gain, dyslipidemia, insulin resistance, and elevated glucose—is more commonly linked to second-generation (atypical) antipsychotics than to older, first-generation ones. This higher risk stems from their pharmacologic effects, especially strong antagonism of 5-HT2C and histamine H1 receptors, which increases appetite and weight gain. These agents can also disrupt glucose metabolism and lipid regulation, contributing to insulin resistance and dyslipidemia. Olanzapine and clozapine are particularly notorious for metabolic disturbances, though other second-generation drugs vary in risk. First-generation antipsychotics tend to cause movement-related side effects rather than metabolic ones, making the metabolic syndrome association weaker in that class. So, the class most strongly associated with metabolic syndrome is the second-generation antipsychotics. In practice, this means careful baseline and periodic monitoring of weight, waist circumference, fasting glucose or HbA1c, and lipids, plus selecting agents with lower metabolic risk when possible and promoting lifestyle interventions.