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Pharmacogenetics of antipsychotic-induced weight gain: review and clinical implications

Abstract

Second-generation antipsychotics (SGAs), such as risperidone, clozapine and olanzapine, are the most common drug treatments for schizophrenia. SGAs presented an advantage over first-generation antipsychotics (FGAs), particularly regarding avoidance of extrapyramidal symptoms. However, most SGAs, and to a lesser degree FGAs, are linked to substantial weight gain. This substantial weight gain is a leading factor in patient non-compliance and poses significant risk of diabetes, lipid abnormalities (that is, metabolic syndrome) and cardiovascular events including sudden death. The purpose of this article is to review the advances made in the field of pharmacogenetics of antipsychotic-induced weight gain (AIWG). We included all published association studies in AIWG from December 2006 to date using the Medline and ISI web of knowledge databases. There has been considerable progress reaffirming previous findings and discovery of novel genetic factors. The HTR2C and leptin genes are among the most promising, and new evidence suggests that the DRD2, TNF, SNAP-25 and MC4R genes are also prominent risk factors. Further promising findings have been reported in novel susceptibility genes, such as CNR1, MDR1, ADRA1A and INSIG2. More research is required before genetically informed, personalized medicine can be applied to antipsychotic treatment; nevertheless, inroads have been made towards assessing genetic liability and plausible clinical application.

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Acknowledgements

Grant supports to this study were provided as follows: CIHR operating grant to DJM (Genetics of antipsychotics induced metabolic syndrome, MOP 89853); NARSAD 2009 Young Investigator Award to DJM, CIHR Michael Smith New Investigator Salary Prize for Research in Schizophrenia to DJM and OMHF New Investigator Fellowship to DJM. We thank Jeffery Powers for graphical design consultation. AKT is a recipient of the Center for Addiction and Mental Health (CAMH) postdoctoral fellowship and a NARSAD 2010 young investigator award.

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Correspondence to D J Müller.

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JLK has received a one time honorarium from Eli Lilly Corporation and has been a consultant to GSK, Sanofi-Aventis and Dainippon-Sumitomo.

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Lett, T., Wallace, T., Chowdhury, N. et al. Pharmacogenetics of antipsychotic-induced weight gain: review and clinical implications. Mol Psychiatry 17, 242–266 (2012). https://doi.org/10.1038/mp.2011.109

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Keywords

  • antipsychotics
  • genetics
  • personalized medicine
  • pharmacogenetics
  • schizophrenia
  • weight gain

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