Olanzapine‐associated dose‐dependent alterations for weight and metabolic parameters in a prospective cohort

Metabolic abnormalities have been associated with olanzapine treatment. We assessed if olanzapine has dose‐dependent effects on metabolic parameters with changes for weight, blood pressure, lipid and glucose profiles being modelled using linear mixed‐effects models. The risk of metabolic abnormalities including early weight gain (EWG) (≥5% during first month) was assessed using mixed‐effects logistic regression models. In 392 olanzapine‐treated patients (median age 38.0 years, interquartile range [IQR] = 26.0–53.3, median dose 10.0 mg/day, IQR = 5.0–10.0 for a median follow‐up duration of 40.0 days, IQR = 20.7–112.2), weight gain was not associated with olanzapine dose (p = 0.61) although it was larger for doses versus ≤10 mg/day (2.54 ± 5.55 vs. 1.61 ± 4.51% respectively, p = 0.01). Treatment duration and co‐prescription of >2 antipsychotics, antidepressants, benzodiazepines and/or antihypertensive agents were associated with larger weight gain (p < 0.05). Lower doses were associated with increase in total and HDL cholesterol and systolic and diastolic blood pressure (p < 0.05), whereas higher doses were associated with glucose increases (p = 0.01). Patients receiving >10 mg/day were at higher EWG risk (odds risk: 2.15, 1.57–2.97). EWG might be prominent in high‐dose olanzapine‐treated patients with treatment duration and co‐prescription of other medications being weight gain moderators. The lack of major dose‐dependent patterns for weight gain emphasizes that olanzapine‐treated patients are at weight gain risk regardless of the dose.