Olanzapine-Induced Weight Gain and Glycolipid Metabolism Aberrations in First-Episode and Antipsychotic-Naïve Schizophrenia Patients: A Longitudinal Study.

Objective: Limited research has delved into the comprehensive impact of monotherapy on weight and glycolipid metabolism in schizophrenia (SCZ) patients. Our study aims to longitudinally investigate the multidimensional effects of olanzapine (OLA) monotherapy on weight and glycolipid metabolism in first-episode and antipsychotic-naïve (FEAN) SCZ patients.

Methods: A total of 74 FEAN-SCZ patients were recruited, as well as 58 sex- and age-matched healthy controls. Eligible patients underwent a 4-week OLA treatment regimen, with weight assessments conducted at baseline and week 4. Moreover, lipid profiles and fasting plasma glucose (FPG) were measured at baseline and week 4. Insulin, leptin (LEP), and adiponectin (APN) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits.

Results: At baseline, FEAN-SCZ patients showed elevated levels of insulin, low-density lipoprotein (LDL), impaired insulin sensitivity, and reduced levels of APN compared to the healthy controls. Following 4-week OLA treatment, patients showed an increase in body mass index (BMI) of 0.96 kg/m2. Additionally, FPG, quantitative insulin sensitivity check index (QUICKI), HOMA-insulin sensitivity index (HOMA-ISI), and fasting plasma glucose to insulin ratio (G/I) displayed significant decreases, while insulin, HOMA-IR, and LEP levels showed significant increases. Stepwise regression analysis revealed that baseline FPG independently predicted the change in BMI after 4 weeks of OLA treatment.

Conclusion: FEAN-SCZ patients exhibited pre-existing alterations in glucose homeostasis. After 4 weeks of OLA treatment, SCZ patients experienced significant weight gain, deteriorating insulin resistance, and increased LEP levels. In addition, baseline FPG emerged as a predictor of BMI changes after 4 weeks of OLA treatment.