Over 300 million people worldwide are suffering from chronic depression. It is also one of the leading causes of disability in US and can be fatal as suicide kills more than 45,000 Americans annually. NIMH psychiatrist Dr. Carlos Zarate and collaborators discovered that a single intravenous dose of the “club drug” ketamine could produce significant antidepressant effects in 71% of the test subjects and remission in 29% patients with treatment-resistant depression (TRD) as compared with placebo. This phenomenal invention paved the way for the development of Spravato®, the esketamine (s-enantiomer of ketamine) based nasal spray, by Janssen Research & Development LLC of Johnson & Johnson. Dr. Husseini Manji, global head of Janssen’s neuroscience division and former NIMH scientist, showed esketamine has rapid and robust antidepressant effects at a low intermittent dosage that can be emitted by a nasal spray. Spravato shows promising anti-depressant effect within 40 minutes that sustained up to 14 days and so can be immensely useful in acute crisis like imminent risk of suicide.  Spravato has received FDA approval with “Fast Track” and “Breakthrough Therapy” designations as a novel treatment for severe depressive disorder on March 5, 2019.  Further research is still needed to elucidate the involved genes, biomarkers and molecular mechanism.

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