Conceivable Mechanisms of Clozapine Propagated Dyslipidemia- A Short Review

Clozapine is the most effective drug for the treatment of refractory schizophrenia, showing a good response in the treatment of patients with resistant schizophrenia, especially in reducing violent, aggressive, and suicidal tendencies. However, treatment with clozapine has been associated with hyperlipidemia especially high triglycerides, obesity, diabetes, and cardiovascular disease. An elevated level of lipids has a direct impact on the improvement of symptoms in schizophrenics treated with clozapine. Although the mechanism is not clear, there is a possibility of serum lipids play a major part in enhancing clozapine's therapeutic activity. The effect of clozapine on phospholipids might indicate that this rise is related to its therapeutic benefit as well. Moreover, increased fatty acids accompanied by a sharp rise in triglycerides, point towards the possible involvement of lipases, which are involved in the storage and release of fatty acids and triglycerides in the adipose tissue. An increase in hepatic lipid synthesis can be another cause of hyperlipidemia and lead to weight gain over a certain period. Lipogenesis and myelin synthesis can also become targets in schizophrenia since myelination and synaptogenesis are essential in the central nervous system. Hence, the upregulation of several genes involved in cholesterol and fatty acid biosynthesis focused, which are proven to be controlled by Sterol regulating element-binding protein transcription factors (SREBP). The antipsychotic drug Clozapine activates this SREBP system. This activation increases lipogenesis which can be one of the mechanisms of action, which in turn could explain the metabolic side effects produced by clozapine.