Effects of olanzapine on metabolic hormones in healthy male subjects

Introduction:

Frequent side effects of atypical antipsychotics including olanzapine are increases of appetite and body weight, elevating the risk of metabolic disorders. We found previously an increase of ghrelin levels after showing pictures with food, but not after neutral pictures in healthy subjects. Now, we tested whether this effect is changed after one week of treatment of healthy subjects with olanzapine. Furthermore the influence of this drug on ghrelin, leptin, insulin and glucose levels was investigated.

Methods:

Blood samples of 10 healthy male subjects (18 – 30yrs.) were taken between 8.00 and 13.00, every 10 to 15 mins at Days -1, -2, 5 and 6. Standardized breakfast and lunch were served. Days -2 and -1 were baseline, without drugs. From Day 0 oral olanzapine dosages were increased stepwise starting with 2.5 mg up to 10 mg at Days 5 and 6. From 10.00 to 10.15 a series of pictures were shown at Days -2 and 5 with neutral content, at Days -1 and 6 with food. A self-assessment questionnaire to visualize appetite was filled in daily by the participants.

Results:

The characteristic meal dependent fluctuations of ghrelin persisted throughout the study. They were found at baseline, and at a lower level at Days 5 and 6 as well. Concentrations of leptin, insulin and glucose increased after olanzapine. Stimulation of ghrelin after pictures showing food was confirmed at baseline and, at a lower level, after olanzapine. The evaluation of the appetite questionnaire showed a significant increase during olanzapine intake.

Conclusion:

Enhancement of ghrelin after pictures showing food was confirmed. This effect was not augmented by olanzapine. Interestingly increased appetite without weight gain is sufficient to prompt changes of metabolic hormones like those described previously after weight gain in patients induced by this drug.