How to Treat Depression: Beyond Conventional Antidepressants

How to Treat Depression: Beyond Conventional Antidepressants

By Rachna Duseja

Depression is a disorder with numerous medicinal remedies that either don’t work or result in relapse for the majority of those affected. As of this year, with the U.S. Food and Drug Administration’s (FDA) support, a new drug might be the answer to how we treat patients with depression.

Earlier this year, a breakthrough occurred in the therapeutic field of depression with Allergan plc, a leading global pharmaceutical company, announcing a phase III clinical trial of its new antidepressant, Rapastinel (GLYX-13). Rapastinel was developed by Naurex, a clinical-stage biopharmaceutical company, which was acquired by Allergan last year. Rapastinel received the first boost in its development in 2014 when it was granted a Fast Track Therapy Designation from the FDA. In January 2016, FDA granted rapastinel a Breakthrough Therapy Designation to fast track this treatment to market.

What Is the Current Scenario in Depression Therapy?

Depression is a devastating condition and has a huge socio-economic burden worldwide. About 70% of the patients are non-responders to conventional antidepressants such as SSRIs/SNRIs (selective serotonin/norepinephrine reuptake inhibitor), and 30% of the patients show remission of their symptoms after treatment. In the patients responsive to treatments, 2-6 weeks is a standard therapeutic time for these antidepressants. Thus, new therapies for depression have to look beyond serotonin/norepinephrine neurotransmitter system.

Why Rapastinel Is Different From Conventional Antidepressants

Rapastinel is different from conventional antidepressants as it works through glutamate neurotransmitter system. Rapastinel is a partial agonist of NMDA receptor (N-methyl-D-aspartate), a subtype of glutamate receptors. In preclinical studies, mice that have taken rapastinel show memory enhancement and antidepressants effects. Phase II clinical trial data looks promising with a rapid therapeutic action of rapastinel and sustained effects lasting for 10 weeks without any hallucinogenic side effects in the patients.
Interestingly, Rapastinel is not the only drug based on the glutamate neurotransmitter system in the pipeline. NRX-1074  from Allergan,  AV-101 (4-Cl-KYN) from Vistatherapeutics, AZD6423 from AstraZeneac, CERC-301 from Cerecor, Esketamine from Janssen Pharmaceuticals are other drugs currently in phase I/II of a clinical trial.

What Next?

The special interest of the FDA has progressed Rapastinel into phase III stage, but the wait has just begun. Only continued testing will reveal whether Rapstinel is a new hope for patients with depression.  


Burgdorf JZhang XLNicholson KLBalster RLLeander JDStanton PKGross ALKroes RAMoskal JR. GLYX-13, a NMDA Receptor Glycine-Site Functional Partial Agonist, Induces Antidepressant-Like Effects Without Ketamine-Like Side Effects. Neuropsychopharmacology (2013) 38, 729–742; doi:10.1038/npp.2012.246

Jeffrey Burgdorf, Xiao-lei Zhang, Katherine L Nicholson, Robert L Balster, J David Leander, Patric K Stanton, Amanda L Gross, Roger A Kroes and Joseph R Moskal. The N-methyl-D-aspartate receptor modulator GLYX-13 enhances learning and memory, in young adult and learning impaired aging rats. Neurobiol Aging. 2011 Apr;32(4):698-706. doi: 10.1016/j.neurobiolaging.2009.04.012.

Image courtesy of

Learn more about PreScouter at

Never miss an insight

Get insights delivered right to your inbox

More of Our Insights & Work

Never miss an insight

Get insights delivered right to your inbox

You have successfully subscribed to our newsletter.

Too many subscribe attempts for this email address.