## Metabolic Side Effects of Antipsychotics **Key Point:** Clozapine carries the highest risk for weight gain, hyperglycemia, dyslipidemia, and metabolic syndrome among all antipsychotics. ### Mechanism of Metabolic Complications Clozapine's metabolic adverse effects are attributed to: 1. **H₁ receptor antagonism** — potent histamine blockade → increased appetite and weight gain 2. **5-HT₂C receptor antagonism** — disrupts satiety signaling 3. **α-adrenergic antagonism** — contributes to sedation and metabolic dysfunction 4. **Direct insulin secretion impairment** ### Comparative Metabolic Risk Profile | Antipsychotic | Weight Gain | Hyperglycemia | Dyslipidemia | Metabolic Syndrome Risk | | --- | --- | --- | --- | --- | | **Clozapine** | ★★★★★ (Highest) | ★★★★ | ★★★★ | Very High | | Olanzapine | ★★★★ | ★★★★ | ★★★★ | High | | Quetiapine | ★★★ | ★★★ | ★★★ | Moderate-High | | Risperidone | ★★ | ★★ | ★★ | Moderate | | Haloperidol | ★ | ★ | ★ | Low | | Aripiprazole | ★ | ★ | ★ | Low | **High-Yield:** Clozapine requires baseline and regular monitoring of: - Fasting glucose and HbA₁c - Lipid profile (total cholesterol, triglycerides, LDL, HDL) - Weight and BMI - Waist circumference **Clinical Pearl:** Despite its metabolic burden, clozapine remains the gold standard for treatment-resistant schizophrenia due to superior efficacy and lower extrapyramidal side effects. **Mnemonic:** **CLOZ** = **C**arb-loving, **L**ipid-raising, **O**besity-prone, **Z**ero metabolic safety. [cite:KD Tripathi 8e Ch 12]
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