Which atypical antipsychotic is most likely to cause metabolic syndrome (weight gain, hyperglycemia, dyslipidemia)?

Explanation

## Metabolic Side Effects of Atypical Antipsychotics **Key Point:** Atypical antipsychotics carry variable risk of metabolic syndrome. Risk correlates with H1 histamine receptor antagonism and α1-adrenergic antagonism, leading to weight gain and insulin resistance. ### Metabolic Risk Ranking | Drug | Weight Gain | Hyperglycemia | Dyslipidemia | Overall Risk | | --- | --- | --- | --- | --- | | **Olanzapine** | Very High | High | High | **HIGHEST** | | **Clozapine** | Very High | High | High | **HIGHEST** | | **Quetiapine** | High | Moderate | Moderate | High | | **Risperidone** | Moderate–High | Moderate | Moderate | Moderate–High | | **Aripiprazole** | Low | Low | Low | **LOWEST** | | **Ziprasidone** | Low | Low | Low | **LOWEST** | | **Lurasidone** | Low | Low | Low | **LOWEST** | **High-Yield:** Olanzapine is the atypical antipsychotic with the highest propensity for metabolic syndrome. Mean weight gain is 4–5 kg over 10 weeks; hyperglycemia and dyslipidemia occur in 10–20% of patients. **Mnemonic:** **CLOZAP** — Clozapine and Olanzapine (the two "heaviest" atypicals): **C**lozapine, **L**arge weight gain, **O**lanzapine, **Z**ero metabolic safety, **A**void if metabolic risk, **P**refer aripiprazole or ziprasidone instead. **Clinical Pearl:** Aripiprazole and ziprasidone are considered metabolically neutral and are preferred in patients with pre-existing diabetes, obesity, or dyslipidemia.