Action of atypical antipsychotics on body weight and associated metabolic factors

Despite having revolutionized the treatment of psychiatric illnesses, atypical antipsychotic agents raise an increasing medical concern regarding their association with prominent body weight gain and metabolic abnormalities resulting from chronic treatment. As a consequence, the use of atypical antipsychotic medication has been linked to a substantial increase in the development of obesity, type 2 diabetes and cardiovascular diseases in patients undergoing therapy. In this study, the primary aim was to develop a mouse model of atypical antipsychotic-induced body weight gain and adiposity. Moreover, the chosen antipsychotic agents, clozapine and olanzapine, were investigated in a fibroblast-like cell line model (7-F2) and in primary bone marrow cells, in order to test a possible direct contribution by these agents in causing adipogenesis and altered lipid metabolism at the cellular level in peripheral tissues. It was found that the ability to produce a reliable and robust mouse model, capable of mimicking the clinical situation was obstructed by variability and inconsistency of the experimental outcomes. This prompts the suggestion that caution should be exercised in the interpretation of results from previous models and also, to question their predictive validity. Furthermore, although a morphological study on 7-F2 cells showed that clozapine and olanzapine do not enhance the differentiation of fibroblastic cells into adipocytes, mRNA over-expression of genes involved in adipocyte formation and metabolism suggest that these antipsychotics incite de novo formation of fat cells in the bone marrow. Overall, although the results are of a preliminary nature, they emphasize the need for in-depth examination of any possibility that clozapine or olanzapine might directly trigger an increase in adipocyte numbers (hyperplasia) or alter adipocyte size (hypertrophy)