Schizophrenia and antipsychotics: metabolic alterations and therapeutic effectivity

Abstract

Schizophrenia presents a high predisposition to present metabolic alterations. This is evidenced in patients never treated with antipsychotics (naïve) and first-degree relatives who do not have the disease, both groups have alterations in the glucose tolerance curve, increase in basal insulin, inflammatory factors and adiponectin (APN). In schizophrenics, antipsychotics increase the frequency of appearance of obesity and metabolic syndrome. These changes are accompanied by a decrease in APN and increase in leptin. Hypertriglyceridemia and hypercholesterolemia correlates with the activation of transcription factor SCREBP1 and 2, in a dose and time dependent manner. The activation of SCREBP increases the expression of enzymes that synthesize triglycerides and cholesterol. There is a strong correlation between the appearance of metabolic alterations and response to treatment in all antipsychotics, this is more evident with clozapine and olanzapine. This relationship between the metabolic effect of the antipsychotic and the effectiveness of the treatment could be related, directly, with the inhibition of GSK3β produced by the antipsychotics.