Using structural equations to test for a direct effect of some antipsychotics on triglyceride levels in drug-naïve first-episode psychosis patients.

Some antipsychotics probably increase the risk of metabolic syndrome. Antipsychotics may differentially influence some elements of metabolic syndrome (obesity, hyperlipidemia, hyperglycemia or hypertension) through various pharmacological mechanisms. In a published study of all first psychotic episodes in a Spanish hospital's catchment area population in Cantabria (Spain), patients were randomly assigned to receive haloperidol (3-9 mg/day), olanzapine (5-20mg/day) or risperidone (3-6 mg/day). In this article, a structural-equation modeling approach tested the mechanistic hypothesis that olanzapine directly (without the mediation of weight gain) increases triglyceride levels, whereas risperidone and haloperidol do not have these effects. A structural equation model was built using the 110 patients whose assigned antipsychotic was not changed during the first 3 months of treatment, and who provided both triglyceride and body mass index (BMI) measurements at baseline and at the end of the 3rd month of treatment. A second structural equation included 72 patients whose antipsychotic was not changed during the first year. After 3 months and controlling for confounders, olanzapine patients had triglyceride levels that were 29.2mg/dL higher [95% confidence interval, (10.9, 47.5)] than those of risperidone patients with comparable baseline triglyceride levels. After 12 months, they were 63.1mg/dL higher (18.6, 107.6) than those of patients with a comparable history of triglyceride values during the first 3 months. Haloperidol effects on triglyceride levels and BMI were no different from those of risperidone. In conclusion, olanzapine increased triglyceride levels without the mediation of weight gain during a one-year study in naïve patients.