Krystal will share the award with colleagues Dennis Charney, MD, and Husseini Manji, MD. They are being honored for their discovery of the rapid antidepressant effects of ketamine and the identification of its efficacy for treatment-resistant depression.

That discovery led to the development of the antidepressant Esketamine, the first mechanistically novel U.S. Food and Drug Administration (FDA)-approved antidepressant in over 50 years.

The award, which recognizes the scientists' achievements, will be presented on October 8 at the academy's annual meeting. It is awarded annually to individuals, groups, or organizations that have demonstrated outstanding achievement in improving mental health.

"It is deeply meaningful to make a discovery that has improved the lives of so many people," said Krystal, who is the Robert L. McNeil, Jr. Professor of Translational Research and professor of psychiatry, neuroscience, and psychology. "I have been moved by the many people treated with ketamine and Esketamine who have reached out to me to share their stories of recovery. This work began here at Yale – at the VA Connecticut Healthcare System – a very special neuroscience and psychiatry community."

The researchers and their collaborators published their findings in 2000 in the journal Biological Psychiatry. They showed that ketamine was a rapid-acting antidepressant, producing improvement within hours of administration and high rates of clinical response within 24 hours of a single dose, whereas standard antidepressants produce clinical response weeks after treatment. Researchers also demonstrated ketamine was effective for treatment-resistant symptoms of depression.

In 2019, the FDA approved Esketamine, which is derived from ketamine, being administered as a nasal spray. The approval came after one study concluded seven in 10 patients who did not respond to other treatments improved on Esketamine.

Krystal said his only regret is that the late Ronald S. Duman, PhD. and George Aghajanian, MD, who collaborated on studies of ketamine and whose work shed much light on the mechanisms underlying the therapeutic actions of the drug, could not be here to share in the celebration.