## Antipsychotic-Induced Metabolic Side Effects **Key Point:** Olanzapine is the atypical antipsychotic with the highest propensity for weight gain and metabolic dysfunction among all antipsychotics. ### Mechanism of Weight Gain Olanzapine causes weight gain through: 1. **H1-receptor antagonism** — increases appetite and reduces satiety signalling 2. **5-HT2C receptor blockade** — impairs hypothalamic appetite suppression 3. **Muscarinic M3 receptor antagonism** — reduces glucose utilization ### Metabolic Complications | Complication | Olanzapine Risk | Timeline | | --- | --- | --- | | Weight gain | Very high (5–10 kg in 6 months) | Weeks to months | | Hyperglycemia | High | Weeks to months | | Dyslipidemia | High (elevated triglycerides) | Weeks to months | | Insulin resistance | High | Weeks to months | **High-Yield:** Olanzapine > Clozapine > Quetiapine > Risperidone > Aripiprazole (in order of metabolic risk). Aripiprazole and ziprasidone are metabolically neutral. **Clinical Pearl:** Patients on olanzapine require baseline and regular monitoring of weight, fasting glucose, lipid panel, and waist circumference per guidelines. ### Comparison with Other Atypicals - **Aripiprazole** — partial D2 agonist; weight-neutral; may cause akathisia - **Ziprasidone** — minimal weight gain; may prolong QTc interval - **Haloperidol** — typical antipsychotic; causes extrapyramidal side effects, not metabolic syndrome [cite:Stahl's Essential Psychopharmacology 6e Ch 5]
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