Understanding the genetic aspects of resistance to antidepressants treatment

Major depression disorder (MDD) is an extremely prevalent disorder and is expected to be the second leading cause of disease burden by 2020 according to the World Health Organisation (WHO). Moreover, this disease burden is predicted to rise in the next 20 years. Antidepressant medications are vital in the therapy of major depression. However, approximately 30-60% of patients treated with current antidepressant drugs fail to attain remission of depressive symptoms leading to drug resistance. Such patients account for a disproportionately great burden of disease, as supported by cost, augmented disability, and suicidal incidents. Antidepressants resistance remains to challenge mental health care professionals, and more relevant research relating newer medications is necessitated to enhance the quality of life of patients with depression. Enhancement in response rates continues the major challenge in antidepressant research, thus a wealth of potentials still exists concerning the antidepressant resistance for the management of major depression. However, the mechanisms causing resistance to antidepressant treatment remain unknown. Hence, clinical and basic research in understanding the fundamental mechanism of antidepressant resistance should remain a key priority. One potential source accounting for these differences in treatment outcome is genetic variations. The pharmacological mechanisms behind antidepressant response are only partly known but genetic factors play a significant role. Future research of risk factors should assist to advance the understanding of the mechanisms underlying drug resistance in mood disorders and contribute to progress their therapeutic management. Thus, psychiatrists could rely on more effective approaches to treat depressive episodes, reducing the incidence of further drug resistance. This review critically summarises the author's view on many aspects of treatment resistance, specific genetic biomarkers, potential strategies and clinical relevance from both clinical and preclinical studies in drug resistance to antidepressant therapies. Finally, this will allow us to suggest possible recommendations and innovative treatment strategies to improve therapeutic outcomes in managing antidepressant resistance.