Drugs, genes and the blues: Pharmacogenetics of the antidepressant response from mouse to man

• Many patients fail to achieve remission with current antidepressant drugs.
• Gene variants associated with the antidepressant response have been identified.
• Both clinical and preclinical approaches have been used to identify these genes.
• The majority of these genes are involved in monoamine neurotransmitter pathways.
• Identification of such genes will guide individualised antidepressant treatment.

While antidepressant drugs are beneficial to many patients, current treatments for depression remain sub-optimal. Up to half of patients with a major depressive episode fail to achieve remission with a first line antidepressant treatment. Identification of the molecular mechanisms that dictate whether a patient will successfully respond to a particular antidepressant treatment while tolerating its side-effects is not only a major challenge in biological psychiatry research but is also one that shows great promise. This review summarises data from both clinical and preclinical studies that point to a role of specific genes in the response and resistance to antidepressant therapeutics. Moreover, we discuss how such findings have increased our understanding of the mechanism of action of antidepressant drugs. Finally, we comment on how this information may potentially influence the future development of personalised medicine approaches for the treatment of depression.