Professor Manji, based in Oxford's Department of Psychiatry, was given the Rhoda and Bernard Sarnat International Prize in Mental Health, alongside Dennis Charney and John Krystal, by the US National Academy of Medicine (NAM).
The prize is 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 US Food and Drug Administration-approved antidepressant in more than 50 years.
The award, which recognises their achievements with medals and US $20,000, will be presented at the NAM’s annual meeting this month.
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 (Food & Drug Administration) “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.
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).
As well as his post at Oxford University, Professor Manji is visiting professor at Duke University, and co-chair of the UK Government's Mental Health Mission. All three winners are members of the National Academy of Medicine, and each is also a recipient of prestigious awards from the Anna-Monika Foundation, Brain and Behaviour Research Foundation, and the American College of Neuropsychopharmacology.
“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 recognises — 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.