2006 Breakthrough: Rapid-Acting Antidepressant Heralded as Biggest Breakthrough in Depression Research in 50 years

Carlos A. Zarate, Jr., M.D. - Brain & behavior research expert on depression
Carlos A. Zarate, Jr., M.D.

Carlos A. Zarate, Jr., M.D., of the National Institute of Mental Health used a 2005 NARSAD Independent Investigator Grant to further studies on what is being heralded by experts as the biggest change in the treatment of depression in the last 50 years. The goal of his project was to develop new, improved and more rapidly-acting therapies for treatment-resistant major depression.

The “change” being referred to is the use of a drug called ketamine to treat resistant depression. In the mid-1990s, NARSAD Independent and Distinguished Investigator Grantee, John H. Krystal, M.D. from Yale University and colleagues began testing ketamine, an anesthetic, on a small cohort of patients with severe depression and immediately noticed positive results. A few years later, Dr. Zarate used his NARSAD Independent Investigator Grant to build on this work.

Earlier research had indicated that the glutamatergic system may play a role in the pathophysiology and treatment of depression, and that agents such as the drug ketamine may be effective at treating depression by more directly reducing glutamatergic neurotransmission. Dr. Zarate led a ground-breaking study with ketamine that showed that a majority of patients, all with treatment-resistant forms of depression, found relief from their symptoms within hours of treatment compared to the several weeks’ lag time often required for traditional antidepressant medications to take effect.  

The work with ketamine is leading researchers to investigate and identify novel mechanisms of action for treatments to effectively treat symptoms of depression. Since as many as 50% of patients do not respond to current antidepressant treatments, this avenue of research is opening crucial new pathways to get more people treated more effectively, more rapidly and with fewer side effects.

In 2011, Dr. Zarate was awarded the Bipolar Mood Disorder Outstanding Achievement Prize (renamed the Colvin Prize for Outstanding Achievement in Mood Disorders Research in 2012). Watch his prizewinner video here.

Read the abstract of this study.

Watch Dr. Zarate’s webinar on Ketamine.

Read our Research News Update for an overview of Ketamine.

Article comments

I am interested in obtaining a grant to use Ketamine in the Emergency Room setting for patients with poorly controlled depression and suicidal ideation. Please contact me at

It is discouraging to see that, despite the passage of time, the FDA still has not approved ketamine for the treatment of depression, much less refractory depression.

It's quite discouraging, especially since many follow up studies have also confirmed the drugs effects. The drug has a long use history and well established safety record. Conversely, weighed against the negative side effects of certain serotonin modulation (not to mention response rate), the FDA still hasn't changed it's opinion on ketamine.

Bloody amazing. . Make noise people . This is so important ..

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