Journal Article

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

Tiwari, A K, Müller, D J, Kennedy, J L, Lett, T A P, Wallace, T J M, Chowdhury, N I

2012

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: Adult and adolescent clinical studies / Antipsychotic Agents - adverse effects / Antipsychotic Agents - classification / Antipsychotic Agents - pharmacokinetics / Antipsychotic drugs / Antipsychotics / Appetite - genetics / Behavioral Sciences / Biogenic Monoamines - metabolism / Biological and medical sciences / Biological Psychology / Biological Transport - genetics / Biotransformation - genetics / Cardiovascular disease / Cardiovascular Diseases - etiology / Caregivers / Clozapine / Compliance / Complications and side effects / Diabetes / Diabetes mellitus / Disease susceptibility / Dopamine D2 receptors / Epigenesis, Genetic / Epigenetics / expert-review / Extrapyramidal system / Genes / Genetic aspects / Genetic Association Studies / Genetic factors / Genetic Predisposition to Disease / Genome-Wide Association Study / Humans / Hypertension / Leptin / Lipid Metabolism - genetics / MDR1 protein / Medical sciences / Medicine / Medicine & Public Health / Mental disorders / Mental health / Meta-Analysis as Topic / Metabolic syndrome / Metabolic Syndrome - etiology / Neuropharmacology / Neurosciences / Neurotransmitter Agents - metabolism / Obesity - chemically induced / Obesity - complications / Obesity - genetics / Olanzapine / Patient Compliance / Personal relationships / Pharmacogenetics / Pharmacology. Drug treatments / Pharmacotherapy / Physiological aspects / Precision Medicine / Psychiatry / Psycholeptics: tranquillizer, neuroleptic / Psychology. Psychoanalysis. Psychiatry / Psychopathology. Psychiatry / Psychopharmacology / Psychoses / Psychotropic drugs / Receptors, Neurotransmitter - genetics / Receptors, Neurotransmitter - metabolism / Risk factors / Risperidone / Schizophrenia / SNAP-25 protein / Stigma / Weight gain / Weight Gain - drug effects / Weight Gain - genetics