Olanzapine Treatment and Weight Gain: Considering the Lipid Side Effects of Antipsychotics

To the Editor: Dr. Wu et al. presented a remarkable pharmacological intervention trial in which metformin administration attenuated several common side effects of olanzapine. Metformin is an appealing option, given 1) the ease of its administration, 2) its relative safety, and 3) the familiarity with its use from a primary care perspective. However, it is important to be familiar with its side effect profile, which may include lactic acidosis.

As the authors thoroughly addressed, most of the metabolic effects of olanzapine are a result of increased weight and increased insulin resistance. However, there are other clinically relevant disturbances such as lipid abnormalities—mainly an increase in triglyceride levels—which require mandatory monitoring (1). This issue was not addressed by the authors.

The Chinese patients in the study had an average body mass index of 21.32. Our heavier outpatients in the United States are even more likely to benefit from a metformin regimen because of the likelihood of higher baseline glucose and insulin measurements (2).

Several other clinical features of the study differed from the clinical characteristics of patients in the United States. First, one can argue that the Chinese patients received both pharmacological and lifestyle modification, since the study indicated that they had at least 30 minutes of daily exercise, which is not equivalent to that of the average schizophrenia patient in the United States. Second, and most relevant to the metformin findings, is the low caloric intake, which was 1,900–2,200 calories per day. The average man in the United States consumes 2,600 calories per day, and thus such a regimen would represent a significant reduction in caloric intake for U.S. patients. Even in an outpatient metformin and lifestyle intervention study (3), Dr. Wu et al. acknowledged that it was not necessary to change the daily caloric intake. Only the nutrient proportion needed to be altered in order to adhere to American Heart Association guidelines. One might speculate that the appetite stimulating properties of olanzapine were constrained by this dietary restriction.

Dr. Wu et al. succeeded in emphasizing the effect of olanzapine on body weight and glucose metabolism, along with the benefits of metformin treatment, to address these issues (3) . However, they did not mention the option of antipsychotic treatment with a more favorable lipid side effect profile, such as aripiprazole, ziprasidone, or paliperidone extended-release (4) .