New Medication for Depression Approaching Approval

Has the "Holy Grail of psychiatry" been discovered?

Posted Feb 14, 2019

When I was in psychiatry residency, I was often told by my attendings that the "Holy Grail of psychiatry" would be finding a medication for the treatment of depression that would work in days rather than taking 4 to 6 weeks as was typical at the time. As of this week, I wonder if we have succeeded in finding this much-needed breakthrough. 

This week an advisory committee of the US Food and Drug Administration (FDA) has recommended the approval of a new type of medication for treatment-resistant depression. Treatment-resistant depression is defined as trying two or more antidepressants without success. Major depressive disorder can be disabling and affects more than 16 million people in the United States. 

This new medication is called esketamine, and it comes in a 28mg nasal spray form. Spravato would be the brand name if it achieves final approval by the FDA.  It has been studied as being given along with a traditional antidepressant

The reason that this is a potentially momentous breakthrough is that current antidepressants take several weeks or even months to achieve a response or the remission of symptoms. This new medication may work in just 24 hours or in days to improve symptoms, thereby providing quick relief of depressive symptoms and potentially preventing countless suicide attempts or suicides. Using current antidepressants, depressed individuals struggle to “wait” for the medication to take effect. 

Esketamine is a glutamate receptor modulator that is thought to restore the connections between certain brain cells in those with major depressive disorder. The FDA has granted Breakthrough Therapy Designation for this new medication, specifically for treatment-resistant depression and major depressive disorder with imminent risk for suicide.  

According to studies with esketamine, patients achieved lower suicide risk scores and lower levels of depression on depression scales within just 4 to 24 hours. Common adverse events were nausea, dizziness, dissociation, unpleasant taste, and headache. 

Ketamine has long been used in anesthesia for it’s sedating properties. For several years, clinics offering subanesthetic doses of intravenous ketamine for treatment-resistant depression have popped up across the U.S. Although ketamine is not and was not FDA-approved for the treatment of depression, it has been quickly becoming the standard of care in psychiatry as clinical and anecdotal evidence has been building. The isomer, esketamine, however, can be given more conveniently in a nasal spray (rather than intravenously) and apparently with less psychoactive effects. 

Ketamine and esketamine have also been studied recently for other disorders. Much of this research is still ongoing. As identified on, one trial of ketamine in those with autism spectrum disorder was completed in 2018, but the research regarding this has not yet been published. There is reason to be hopeful that esketamine will be approved by the FDA as recommended by its committee, and that new uses will be pursued. 


1.       FDA Panels Endorse Ketamine Nasal Spray for Resistant Depression- Medscape- Feb. 13, 2019.

2.       The Janssen Pharmaceutical Companies of Johnson & Johnson News Release., Feb 12, 2019.