Role of genetic polymorphisms related to neurotransmitters and cytochrome P-450 enzymes in response to antidepressants.
While pharmacological treatment of major depressive disorder with antidepressants continues to improve, responses remain poor in 30-50% of patients, with many patients discontinuing their medication due to distressing side effects. Drug response can be influenced by genetic factors and several physiological and environmental factors, including age, renal and liver function, nutritional status, smoking and alcohol consumption. In particular, genetic factors can be considered to contribute to antidepressant response. Genetic differences in response to antidepressants may be due to variants that affect the function of genes involved in both pharmacokinetics and pharmacodynamics. Genetic variants affecting the metabolism of antidepressants may change pharmacokinetic factors, and polymorphisms that affect the function of receptors and signal transduction molecules may alter pharmacodynamics. Both pharmacokinetic and pharmacodynamic change can affect the efficacy and side effects of antidepressants.
Lee
Min-Soo
MS
Depression Center, Clinical Research Center for Depression, Institute of Human Behavior and Genes, College of Medicine, Korea University, Seoul, Korea. leeminso@korea.ac.kr
D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000235:genetics; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000235:genetics; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011985:Receptors, Serotonin / Q000235:genetics / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; C454420:G-protein beta3 subunit; D011985:Receptors, Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D003577:Cytochrome P-450 Enzyme System; D014365:Tryptophan Hydroxylase; D020962:Heterotrimeric GTP-Binding Proteins