Pharmacogenetics of antipsychotic-induced side effects.
Currently available antipsychotic drugs (APDs) carry significant though highly variable, liability to neurologic and metabolic side effects. Pharmacogenetics approaches offer the possibility of identifying patient-specific biomarkers for predicting risk of these side effects. To date, a few single nucleotide polymorphisms (SNPs) in a handful of genes have received convergent support across multiple studies. The primary focus has been on SNPs in dopamine and serotonin receptor genes: persuasive meta-analytic evidence exists for an effect of the dopamine D2 and D3 receptor genes (DRD2 and DRD3) in risk for tardive dyskinesia (TD) and for an effect of variation at the 5-HT2C receptor gene (HTR2C) for liability to APD-induced weight gain. However, effect sizes appear to be modest, and pharmacoeconomic considerations have not been sufficiently studied, thereby limiting clinical applicability at this time. Effects of these genes and others on risk for TD, extrapyramidal side effects, hyperprolactinemia, and weight gain are reviewed in this article.
Center for Translational Psychiatry, Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Glen Oaks, NY, USA.
Todd
T
Lencz
Anil K
AK
Malhotra
D017109:Akathisia, Drug-Induced / Q000209:etiology / Q000235:genetics; D000818:Animals; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001480:Basal Ganglia Diseases / Q000139:chemically induced / Q000235:genetics; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy; D015201:Meta-Analysis as Topic; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D011388:Prolactin / Q000378:metabolism; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050637:Receptors, Dopamine D3 / Q000235:genetics; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics
D014150:Antipsychotic Agents; D044405:Receptor, Serotonin, 5-HT2C; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D011388:Prolactin