Second-Generation Antipsychotics and Dysregulation of Glucose Metabolism: Beyond Weight Gain

Abstract

Second-generation antipsychotics (SGAs) are the cornerstone of treatment for schizophrenia because of their high clinical efficacy. However, SGA treatment is associated with severe metabolic alterations and body weight gain, which can increase the risk of type 2 diabetes and cardiovascular disease, and greatly accelerate mortality. Several underlying mechanisms have been proposed for antipsychotic-induced weight gain (AIWG), but some studies suggest that metabolic changes in insulin-sensitive tissues can be triggered before the onset of AIWG. In this review, we give an outlook on current research about the metabolic disturbances provoked by SGAs, with a particular focus on whole-body glucose homeostasis disturbances induced independently of AIWG, lipid dysregulation or adipose tissue disturbances. Specifically, we discuss the mechanistic insights gleamed from cellular and preclinical animal studies that have reported on the impact of SGAs on insulin signaling, endogenous glucose production, glucose uptake and insulin secretion in the liver, skeletal muscle and the endocrine pancreas. Finally, we discuss some of the genetic and epigenetic changes that might explain the different susceptibilities of SGA-treated patients to the metabolic side-effects of antipsychotics.

Dopaminergic antagonists inhibit bile chemotaxis of adult Clonorchis sinensis and its egg production

“…The CsAds were incubated, 5 flukes each, in a petri-dish (35 × 10 mm, Falcon, Corning, NY) containing 5 mL of 1× Locke's solution. The survival rate and activity of the adult flukes were checked under a stereomicroscope every 1 h for 12 h, and then at 18,24,30,42,54,66,78,90,102, and 126 h (S1 Fig). The solution was replaced with fresh solution at every time point.…”

“…These drugs significantly suppressed egg production of the CsAds in the experimental rabbits. In general, antipsychotic drugs are associated with extrapyramidal side effects, movement disorders, and metabolic disorders in the course of schizophrenic patients treatment [30]. Therefore, the anthelminthic efficacy of dopaminergic antagonists toward C. sinensis needs to be investigated further.…”

Assessment of the ameliorative effect of Hypericum perforatum on olanzapine-induced hepatic oxidative stress and metabolic abnormalities in experimental male albino rats

“…Atypical drugs as OLZ are associated with different metabolic disorders, including hypertriglyceridemia, hyperglycemia, and weight gain [6]. These metabolic disturbances should get a great concern with the increased hazard of obesity complications and death [7]. Unfortunately, exercise and diet regulation didn't play an important role in obesity-induced by antipsychotic drugs [8].…”

Long-Term Assessment of Lurasidone in Schizophrenia: Post Hoc Analysis of a 12-Month, Double Blind, Active-Controlled Trial and 6-Month Open-Label Extension Study

“…Schizophrenia is a severe and chronic mental illness that affects approximately 20 million people worldwide [1]. People with schizophrenia are 2-3 times as likely to die early as the general population, resulting in a reduced life expectancy of 10-20 years [2,3]. This reduction in life expectancy largely results from an increased likelihood of cardiovascular disease, diabetes mellitus, and other physical conditions, exacerbated by insufficient prevention of modifiable risk factors [3,4].…”

“…People with schizophrenia are 2-3 times as likely to die early as the general population, resulting in a reduced life expectancy of 10-20 years [2,3]. This reduction in life expectancy largely results from an increased likelihood of cardiovascular disease, diabetes mellitus, and other physical conditions, exacerbated by insufficient prevention of modifiable risk factors [3,4]. Cardiovascular disease is the leading cause of death in schizophrenia, individuals with the disorder having significantly higher risks of metabolic syndrome, abdominal obesity, dyslipidaemia, and hypertension than the general population [5][6][7][8].…”