Which antipsychotic is most commonly associated with metabolic syndrome, including weight gain, hyperglycemia, and dyslipidemia?

Explanation

## Metabolic Side Effects of Antipsychotics **Key Point:** Olanzapine carries the highest risk of metabolic complications among all antipsychotics, particularly weight gain and glucose dysregulation. ### Metabolic Risk Stratification | Antipsychotic | Weight Gain | Hyperglycemia | Dyslipidemia | Overall Risk | |---|---|---|---|---| | Olanzapine | +++ | +++ | +++ | **Very High** | | Clozapine | +++ | ++ | ++ | **Very High** | | Risperidone | ++ | ++ | ++ | **High** | | Quetiapine | ++ | ++ | ++ | **High** | | Haloperidol | + | + | + | **Low** | | Aripiprazole | + | + | + | **Low** | | Ziprasidone | + | + | + | **Low** | **High-Yield:** Olanzapine and clozapine are the "metabolic villains" — both are atypical antipsychotics with potent H1-receptor and muscarinic antagonism, driving appetite stimulation and insulin resistance. Weight gain can exceed 10 kg within the first 6 months of therapy. ### Mechanism 1. **H1-receptor antagonism** → increased appetite and decreased satiety 2. **Muscarinic M3 antagonism** → impaired glucose homeostasis 3. **5-HT2C antagonism** → dysregulation of hypothalamic appetite control **Clinical Pearl:** Metabolic monitoring (fasting glucose, lipid panel, BMI) should begin at baseline and be repeated at 3, 6, and 12 months for all patients on olanzapine or clozapine [cite:Maudsley Guidelines 2021]. **Tip:** When olanzapine is clinically necessary, consider switching to aripiprazole or ziprasidone if metabolic side effects emerge, or co-prescribe metformin for glucose protection.