Mechanisms underlying metabolic disturbances associated with psychosis and antipsychotic drug treatment

REYNOLDS, Gavin and MCGOWAN, Olga (2017). Mechanisms underlying metabolic disturbances associated with psychosis and antipsychotic drug treatment. Journal of Psychopharmacology, 31 (11), 1430-1436.

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The increase in cardiovascular disease and reduced life expectancy in schizophrenia likely relate to an increased prevalence of metabolic disturbances. Such metabolic risk factors in schizophrenia may result from both symptom-related effects and aetiological factors. However, a major contributory factor is that of treatment with antipsychotic drugs. These drugs differ in effects on body weight; the underlying mechanisms are not fully understood and may vary between drugs, but may include actions at receptors associated with the hypothalamic control of food intake. Evidence supports 5-hydroxytryptamine receptor 2C and dopamine D2 receptor antagonism as well as antagonism at histamine H1 and muscarinic M3 receptors. These M3 receptors may also mediate the effects of some drugs on glucose regulation. Several antipsychotics showing little propensity for weight gain, such as aripiprazole, have protective pharmacological mechanisms, rather than just the absence of a hyperphagic effect. In addition to drug differences, there is large individual variation in antipsychotic drug-induced weight gain. This pharmacogenetic association reflects genetic variation in several drug targets, including the 5-hydroxytryptamine receptor 2C, as well as genes involved in obesity and metabolic disturbances. Thus predictive genetic testing for drug-induced weight gain would represents a first step towards personalised medicine addressing this severe and problematic iatrogenic disease.

Item Type: Article
Additional Information: ** From Crossref via Jisc Publications Router.
Uncontrolled Keywords: Pharmacology (medical), Pharmacology, Psychiatry and Mental health
Research Institute, Centre or Group - Does NOT include content added after October 2018: Biomedical Research Centre
Identification Number:
Page Range: 1430-1436
SWORD Depositor: Jill Hazard
Depositing User: Jill Hazard
Date Deposited: 19 Sep 2017 16:41
Last Modified: 18 Mar 2021 17:00

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