Pharmacogenetic treatment of depressive disorders

Whilst the efficacy of antidepressant-based treatments of major depressive disorder continues to improve, responses remain poor in 30-50% of patients, with many patients discontinuing the medication due to distressing side effects. Drug responses can be influenced by genetic factors and several physiological and environmental factors, including age, renal and liver function, nutritional status, smoking and alcohol consumption. Antidepressants have a multifactorial mechanism of action and their phenotypic expression can be affected by several different genes. Most pharmacogenetic investigations into antidepressants have been conducted on candidate genes from the monoaminergic pathway. Antidepressants are thought to regulate monoaminergic transmission, and this review highlights pharmacogenetic studies into the effects of genes related to the monoaminergic pathway, such as the serotonin transporter, serotonin receptors of the norepinephrine transporter, tryptophan hydroxylase, the β3 subunit of G protein and brain-derived neurotrophic factor, on the action of antidepressants.