Investigational drugs for treating major depressive disorder

ABSTRACT

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.

KEYWORDS:

• Major depression
• preclinical and clinical studies
• opioid receptors
• glutamatergic receptors
• neurotrophins
• triple reuptake inhibitors

Article highlights

• Major depression is a severe mood disorder that requires immediate clinical investigation.

• Various conventional antidepressant molecules are available for the management of major depression; however, 30–40% of these patients do not respond to the monotherapy and therefore requires the addition of 2nd drug in their dosing regimen.

• There is a continuous effort from researchers exploring the novel drug targets as well as drugs for patients who do not respond to drug therapy

• Some of these investigational targets include, opioidergic system, ionotropic and metabotropic glutamatergic receptors, neurotophins, triple reuptake inhibitors and many more.

• The investigational molecules discussed in this article include, ALKS 5461, CERC-501, rapastinel, dueteriated dextromethorphan, CERC-301, basimglurant, amitifadine, tedatioxetine and ansofaxine.

• Amitifadine, ALKS-5461 and rapastinel are in late clinical trials. These drugs may soon show up in the clinics for the treatment of major depression.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.