Pharmacogenetics-Guided Dose Modifications of Antidepressants

The efficacy of a drug therapy is influenced by many different factors, such as age, weight, comorbidity, and comedication, which vary among patients, as do the fixed parameters of sex and genotype. Enzymes involved in drug metabolism are genetically polymorphic, meaning that their activities differ depending on certain genotypes. Drugs are metabolized slowly in individuals carrying a genetic polymorphism that causes absent or decreased enzyme activity, and these individuals are at an increased risk for adverse drug reactions or therapeutic failure. However, drug therapy could be ineffective if the drug is metabolized too quickly because of a genetic polymorphism. Knowledge of these polymorphisms before beginning a drug therapy could help in choosing the right agent at a safe dosage, especially those with a narrow therapeutic index and a high risk for the development of adverse drug effects. Particularly, two polymorphic drug metabolizing enzymes, belonging to the cytochrome P450 (CYP) family, are responsible for the metabolism of many antidepressant drugs: CYP2D6 and CYP2C19. In addition to antidepressive drugs, several drugs used in cancer therapy, β-blockers, proton pump inhibitors, and opioid analgesics are metabolized by these enzymes.