TREATMENT · Training European Network: Metabolic Dysfunctions associated with Pharmacological Treatment of Schizophrenia

Training European Network: Metabolic Dysfunctions associated with Pharmacological Treatment of Schizophrenia

Drugs are prescribed based on their beneficial effects. However, differences in response among patients are common. A major factor conferring variability is drug induced liver injury, particularly in chronic treatments and in patients treated with multiple drugs. Liver injury impacts glucose and lipid homeostasis, frequently leading to diabetes and cardiovascular (CV) complications. Schizophrenia is a chronic and disabling disorder affecting about 1% of the population. It captures most of the resources available to psychiatric services. It is the fourth leading cause of disease burden accounting for 4.4% of total disability adjusted life years (DALYs) lost, in 2000. It has been estimated that by 2020 it will be the second leading cause of DALYs lost. Treatments relieve symptoms, but are taken for life. Metabolic dysfunctions are highly prevalent in schizophrenic patients. In fact, diabetes and schizophrenia have for long been linked. Metabolic syndrome Incidence in this population is twice that of the general population, suggesting it might be secondary to the effects of medication. Over 60 antipsychotic drugs are available and are divided into 2 groups: first generation and second-generation agents (SGAs). SGAs are now the main therapeutic option for schizophrenia, bipolar disorders and other psychotic conditions. However, questions remain regarding their exact mechanism of action. Metabolic derangements from antipsychotic agents have been the focus of interest for years. Children and adolescents receiving SGAs are particularly vulnerable. Antipsychotic poly-pharmacy, a common practice, can also be associated with increased risk of pre-metabolic syndrome. Of all SGAs, Olanzapine increases weight gain and cholesterol levels most, while Aripiprazol shows the least reported weight gain. While drug-induced weight gain has been associated with T2D, T2D also occurs in absence of weight gain, indicating that metabolic disturbances are not only related to the changes in diet and activity that occur in response to the treatment. Metabolic effects derived from SGAs or other long-term treatments could result from a limited capacity of the liver to catabolize the drug and neutralize toxic intermediates. The cross-stalk between metabolic pathways and neurotransmitters also deserves further investigation. TREATMENT aimed to train ESRs in an area of research that currently lacks highly trained professionals at the interphase of basic, translational and applied pharmacology. Its mission is to develop protocols to match the treatment to the patient. It focuses on SGAs, since they are associated with severe metabolic side effects.

Data: CORDIS, © European Union