Olanzapine-Induced Elevation of Plasma Triglyceride Levels

To the Editor: The relatively recent introduction of the newer atypical antipsychotic medications—risperidone, olanzapine, quetiapine—has resulted in a shift in the prescribing practices of psychiatrists. This is likely because of both efficacy and safety. These drugs have demonstrated efficacy at least comparable, and possibly superior, to that of typical antipsychotic drugs, with less likelihood of inducing extrapyramidal side effects. One of the most clinically relevant side effects of the atypical antipsychotics at recommended doses has been weight gain. There are limited direct comparisons of the atypical antipsychotics, although olanzapine has been associated with greater weight gain than risperidone (1). The significance of this beyond cosmetic effects is unknown. This letter describes how long-term olanzapine treatment may affect lipid profiles in a group of chronically institutionalized patients with schizophrenia.

Nine fasting patients (seven men, two women), whose mean age was 41 years (range=24 to 67 years), had blood drawn for plasma lipid panels and their weight measured before starting treatment with olanzapine. This information was obtained by means of routine hospital data collection; therefore, written informed consent was not obtained. The panels consisted of cholesterol, triglyceride, and high- and low-density lipoprotein levels. Lipid panel results and patients’ weights were reexamined after an average of 16 months of treatment. The patients’ mean dose of olanza­pine was 19 mg/day (range=10 to 30). Patients also received adjunctive treatments, with mood stabilizers most often prescribed.

Cholesterol levels, although elevated at baseline, and high- and low-density lipoprotein levels remained essentially unchanged. However, triglyceride levels (normal range=25 to 200 mg/dl) increased from a mean of 170 mg/dl (range=69 to 385) to a mean of 240 mg/dl (range=135 to 369). Five of the nine patients had at least a 50% increase in their levels, although this did not reach statistical significance (paired t test). Consistent with previous reports, patients had a mean weight gain of 22 lb.

This report suggests that olanzapine treatment may result in a marked increase in triglyceride levels for some patients. Whether these results can be generalized to less severely ill patients receiving monotherapy is unknown. In univariate analysis, elevated serum triglyceride levels are correlated with a risk for coronary artery disease, although there is much controversy over the link when other lipid risk factors are added to the model (2, 3). Given our limited understanding of the long-term side effects of olanzapine, monitoring lipid profiles may be advisable. This is likely most important for patients with other nonlipid risk factors, such as a family history of early-onset arteriosclerotic ­complications (4).