Effect of olanzapine on feeding and selected biochemical factors related to weight gain

Abstract

Olanzapine is an atypical antipsychotic drug exhibiting a low incidence of extrapyramidal side effects. It is not only effective in treating positive symptoms of schizophrenia, but also more efficacious against negative and depressive symptoms than classical antipsychotics. Olanzapine has been recommended as the first-line drug for the treatment of schizophrenia. Unfortunately, a common side effect of olanzapine, namely weight gain, has also been observed. A comprehensive literature analysis revealed that olanzapine induced higher weight gain than most other antipsychotics, only second to clozapine. The incidence of olanzapine-induced weight gain and related diseases, such as diabetes and cardiovascular diseases, is higher than that of the general population. These unwanted side effects have decreased the adherence to treatment. Many clinical observations and preliminary animal studies have attempted to elucidate the possible mechanism involved. To date, the mechanism for olanzapine-induced weight gain remains unclear.This research project utilizes an animal model to investigate the possible mechanism of olanzapine-induced weight gain. The specific research objectives include: 1) does olanzapine affect feeding behavior; 2) can olanzapine influence the levels of glucose and triglyceride; 3) are cytokines, such as insulin, leptin, and TNF-Ą involved in olanzapine-induced weight gain; 4) how does olanzapine affect adipose tissue? An olanzapine-induced weight gain animal model has been established in the present investigation. An increase in food and water intake and increase in fat deposition accompanied with weight gain after treatment were observed. No significant increase in levels of glucose and triglyceride was detected. The changes of insulin and leptin levels in blood suggest that olanzapine may affect the endocrine system. A dramatic morphological alteration of adipose tissue by olanzapine was serendipitously observed. Immunohistochemical staining revealed that olanzapine stimulated collagen VI expression and deposition in the extracellular matrix suggesting that adipocyte differentiation may be enhanced. The effect of olanzapine on fat deposition might play a critical role in olanzapine-induced weight gain. The data from adipose tissue have provided a new clue on future research in understanding the mechanism of olanzapine-induced weight gain. Due to limitation of small number of animals and relatively short term of treatment, a large variation in groups diminished the power of analysis regarding the effects of olanzapine related to weigh gain.