Pharmacogenetics of anxiolytic drugs

Acute and chronic anxiety represents the core symptoms in anxiety disorders. Anxiolytic pharmacological treatment mainly consists in administration of benzodiazepines and antidepressants. Whereas benzodiazepines show little, antidepressants show a relative large interindividual variability in terms of drug response where about one-third of patients do not respond at all. With no meaningful predictors available, there is increasing hope that genetics can help in adding important pieces of information in order to avoid lengthy drug trials and/or to avoid side effects. However, only few studies have been conducted with antidepressants and benzodiazepines in anxiety disorders. Similar to studies in major depression, some significant findings indicate that presence of the long allele of the serotonin transporter (5-HTT) gene is associated with favorable response. Other significant findings pointed to the serotonin 2A (5-HT2A) receptor and to the tryptophan hydroxylase (TPH1) genes. To date, the most promising strategy in clinical practice appears to incorporate testing of functional CYP450 gene variants (CYP1A2, CYP3A4, CYPD26 and CYP2C19) to avoid over- or under-dosing in poor or rapid metabolizers, respectively. As research progresses, it is likely that further gene variants will be detected that in conjunction with clinical variables will lead to algorithms allowing for individualized anxiolytic drug treatment.