Antipsychotics and glucose metabolism: how brain and body collide

Since the serendipitous discovery of the first antipsychotic (AP) drug in the 1950s, APs remain the cornerstone of treatment for schizophrenia. A shift over the past two decades away from first-generation, conventional APs to so-called "atypical" (or 2nd/3rd generation) APs parallels ackno...

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Bibliographic Details
Published in:American journal of physiology: endocrinology and metabolism 2019-01, Vol.316 (1), p.E1-E15
Main Authors: Kowalchuk, Chantel, Castellani, Laura N, Chintoh, Araba, Remington, Gary, Giacca, Adria, Hahn, Margaret K
Format: Article
Language:English
Subjects:
Antagonism
Antipsychotics
Autonomic nervous system
Behavior disorders
Brain
Diabetes mellitus
Diabetes mellitus (non-insulin dependent)
Drug metabolism
Drugs
Glucose
Glucose metabolism
Health risks
Homeostasis
Illnesses
Insulin
Insulin resistance
Medical treatment
Mental disorders
Metabolic disorders
Metabolism
Mind body relationship
Neurotransmitters
Schizophrenia
Side effects
Weight
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Summary:Since the serendipitous discovery of the first antipsychotic (AP) drug in the 1950s, APs remain the cornerstone of treatment for schizophrenia. A shift over the past two decades away from first-generation, conventional APs to so-called "atypical" (or 2nd/3rd generation) APs parallels acknowledgment of serious metabolic side-effects associated in particular with these newer agents. As will be reviewed, AP drugs and type 2 diabetes are now inextricably linked, contributing to the three- to fivefold increased risk of type 2 diabetes observed in schizophrenia. However, this association is not straightforward. Biological and lifestyle-related illness factors contribute to the association between type 2 diabetes and metabolic disease independently of AP treatment. In addition, APs have a well-established weight gain propensity which could also account for elevated risk of insulin resistance and type 2 diabetes. However, compelling preclinical and clinical evidence now suggests that these drugs can rapidly and directly influence pathways of glucose metabolism independently of weight gain and even in absence of psychiatric illness. Mechanisms of these direct effects remain poorly elucidated but may involve central and peripheral antagonism of neurotransmitters implicated not only in the therapeutic effects of APs but also in glucose homeostasis, possibly via effects on the autonomic nervous system. The clinical relevance of studying "direct" effects of these drugs on glucose metabolism is underscored by the widespread use of these medications, both on and off label, for a growing number of mental illnesses, extending safety concerns well beyond schizophrenia.
ISSN:0193-1849
1522-1555
DOI:10.1152/ajpendo.00164.2018