The National Academy of Medicine (NAM) today announced that Dennis Charney, John Krystal, and Husseini Manji are the recipients of the 2023 Rhoda and Bernard Sarnat International Prize in Mental Health for their discovery of the rapid antidepressant effects of ketamine and the identification of its efficacy for treatment-resistant depression (TRD), which led to the development of the antidepressant esketamine, the first mechanistically novel U.S. Food and Drug Administration-approved antidepressant in over 50 years. The award, which recognizes their achievements with medals and $20,000, will be presented at the NAM’s annual meeting on Oct. 8.

The award-winning team of scientists and collaborators 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. This speed contrasts with standard antidepressants that produce clinical response only after weeks of treatment. In addition, members of the group demonstrated that ketamine was effective for treatment-resistant symptoms of depression. At Janssen Pharmaceutical Companies of Johnson & Johnson (now Johnson & Johnson Innovative Medicine), members of the team developed a novel, practical intranasal version of esketamine (Spravato), the first neuroscience medication to receive FDA “breakthrough designation.” They further showed that Spravato produced robust and rapid antidepressant responses, and when administered intermittently over a longer term in TRD patients, it prevented relapses. Spravato was also investigated in major depressive disorder patients with active suicidal ideation or intent. These studies led to a second FDA indication for Spravato for depressive symptoms in adults with major depressive disorder with suicidal thoughts or actions.

Depression is among the most common medical conditions, with a lifetime prevalence in over 20 percent of the population. At least one-third of people experiencing depression do not achieve remission despite multiple trials of standard medications. The discovery of the rapid antidepressant effects of ketamine has the potential to help many individuals who have not responded to other treatments. It also stimulated translational neuroscience and led to new insights into the biology of depression and discoveries of novel mechanisms of antidepressant action. Further, the development of Spravato enabled the testing of other psychoactive drugs that have reached Phase III clinical trials, including psilocybin and methylenedioxymethamphetamine (MDMA).

Charney is Anne and Joel Ehrenkranz Dean and professor in the departments of psychiatry, neuroscience, and pharmacological sciences at Icahn School of Medicine at Mount Sinai and president for Academic Affairs at Mount Sinai Health System. Krystal is Robert L. McNeil Jr. Professor of Translational Research, professor of psychiatry, neuroscience, and psychology, and chair, department of psychiatry, Yale University. Manji is a professor at Oxford University, visiting professor at Duke University, and co-chair, U.K. Government Mental Health Mission. All three are members of the National Academy of Medicine, and each is also a recipient of prestigious awards from the Anna-Monika Foundation, Brain and Behavior Research Foundation, and the American College of Neuropsychopharmacology. Charney is a member of the National Academy of Inventors, and Krystal is a fellow of the American Association for the Advancement of Science.

“Congratulations to this exceptional team, for their discovery is having a remarkable impact not only on the public health challenge of depression but also on vital research on treating other psychiatric and mental health conditions,” said NAM President Victor J. Dzau. “This groundbreaking research by Drs. Charney, Krystal, and Manji constitutes one of the most important therapeutic advances in psychiatry in the current era, making them highly deserving of this recognition.”

Since 1992, the Sarnat Prize has been presented to individuals, groups, or organizations that have demonstrated outstanding achievement in improving mental health. The prize recognizes — without regard for professional discipline or nationality — achievements in basic science, clinical application, and public policy that lead to progress in the understanding, etiology, prevention, treatment, or cure of mental disorders, or to the promotion of mental health. As defined by the nominating criteria, the field of mental health encompasses neuroscience, psychology, social work, nursing, psychiatry, and advocacy.

The award is supported by an endowment created by Rhoda and Bernard Sarnat of Los Angeles. Rhoda Sarnat was a licensed clinical social worker, and Bernard Sarnat was a plastic and reconstructive surgeon and researcher. The Sarnats’ concern about the destructive effects of mental illness inspired them to establish the award.  This year’s selection committee was chaired by Peter R. MacLeish, professor, department of neurobiology, Morehouse School of Medicine.

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