Investigational drugs for treating major depressive disorder.

INTRODUCTION: Treatment of patients suffering from major depression could be highly challenging for psychiatrists. Intractability as well as relapse is commonly seen among these patients, leading to functional impairment and poor quality of life. The present review discusses some of the novel investigational drugs that are under pre-clinical or clinical phases in the treatment of major depression. Areas covered: Molecules belonging to different classes such as triple reuptake inhibitors, opioid receptors, ionotropic and metabotropic glutamate receptors, and neurotrophin in the treatment of major depression are covered in this article. Expert opinion: Although the historical discovery of earlier antidepressant molecules (iproniazid and imipramine) is through serendipitous discovery, the present research focuses on discovering novel molecules based on our current pathophysiological knowledge of the disease condition. The fast-acting antidepressant property of N-methyl-d-aspartate (NMDA) receptor molecules, including ketamine is an exciting area of research. Other drug molecules such as amitifadine (triple reuptake inhibitor), ALKS-5461 (kappa receptor antagonist and mu opioidergic receptor agonist), rapastinel (NMDA glutamatergic receptor modulator) are under Phase-III clinical trials and could be approved in the near future for the treatment of major depression.