Association between olanzapine concentration and metabolic dysfunction in drug-naive and chronic patients: similarities and differences

Second-generation antipsychotics are widely used to treat schizophrenia but their use could induce metabolic dysfunction. To balance efficacy and side effects, various guidelines recommend the use of therapeutic drug monitoring. Given the controversial relationship between olanzapine serum concentration and metabolic dysfunction, its use in clinical practice is still debated. To address this issue, we conducted a prospective cohort study to explore the associations in patients with schizophrenia. Specifically, first-episode drug-naive patients and patients with chronic schizophrenia were recruited. All participants received olanzapine monotherapy for 8 weeks. Anthropometric parameters and metabolic indices were tested at baseline and at week 8, and olanzapine serum concentration was tested at week 4. After 8 weeks of observation, body weight and BMI increased significantly in drug-naive patients. Moreover, triglycerides and LDL increased significantly in both drug-naive and chronic patients. Among chronic patients, those who have never used olanzapine/clozapine before had a significantly higher increase in weight and BMI than those who have previously used olanzapine/clozapine. Furthermore, olanzapine concentration was associated with changes in weight, BMI, and LDL levels in the drug-naive group and glucose, triglyceride and LDL levels in chronic patients who have not used olanzapine/clozapine previously. In conclusion, the metabolic dysfunction induced by olanzapine is more severe and dose-dependent in drug-naive patients but independent in patients with chronic schizophrenia. Future studies with a longer period of observation and a larger sample are warranted.