Olanzapine

Among the highest of any psychotropic medication. Often cited in the range of 5-10 kg in the first year, with substantial individual variation. Weight gain is rapid early (first 3-6 months) and continues to accumulate. Driven by H1 and 5-HT2C antagonism plus apparent direct metabolic effects. This is not a rare side effect. It is an expected pharmacological consequence.

Olanzapine raises fasting glucose and can precipitate new-onset type 2 diabetes, including cases of diabetic ketoacidosis. The risk appears to exceed what weight gain alone would predict, suggesting direct effects on insulin metabolism. Monitor fasting glucose at baseline, 12 weeks, and at least annually thereafter.

Clinically significant increases in total cholesterol, LDL, and triglycerides. Contributes to long-term cardiovascular risk. Monitor fasting lipid panel at baseline, 12 weeks, and at least annually.

H1-mediated. Often severe in the first few weeks and may improve partially over time. Bedtime dosing is standard. Can impair daytime functioning.

Alpha-1 mediated. Risk during initiation and dose increases. Relevant in elderly patients and those on antihypertensives. Counsel patients to rise slowly.

Dry mouth, constipation, urinary retention from moderate muscarinic antagonism. Usually manageable but can be clinically significant in elderly patients or those on other anticholinergic medications.

Olanzapine's EPS rate is lower than haloperidol or risperidone, partly due to its favorable 5-HT2A/D2 ratio and partly due to its intrinsic anticholinergic activity. However, EPS is not zero, particularly at higher doses.

Olanzapine causes less prolactin elevation than risperidone. Prolactin effects are typically mild and transient. This is a relative advantage when comparing antipsychotic options.