The U.S. Food and Drug Administration approved Spravato (esketamine) nasal spray, in conjunction with an oral antidepressant, for the treatment of depression in adults who have tried other antidepressant medicines but have not benefited from them (treatment-resistant depression). 

Esketamine is made from a drug called ketamine, an anesthetic that has also been used for many years to treat depression. But it wasn’t until recently that esketamine, a more potent version of ketamine, earned FDA approval specifically for use as a nasal spray for those with treatment-resistant depression.

With the nasal spray, you give yourself three doses, spaced five minutes apart, under provider supervision. You remain in the clinic under provider observation until potential side effects have passed.

Esketamine must be used in conjunction with a conventional antidepressant. The intention is that esketamine provides rapid relief from depression symptoms until the other medication takes effect.

Usually, the treatment is given twice a week for the first month, and then if it is successful it is continued at decreased frequency in a maintenance phase for a few weeks or months with dosing and frequency determined by treatment response. Typically, this might mean a decrease to weekly treatments, then every two weeks, then monthly, etc. 

You and your provider will discuss recommendations. 

Esketamine works in a similar fashion, but unlike other antidepressants it increases levels of glutamate, the most abundant chemical messenger in the brain. The result? A greater impact on more brain cells at one time.

Common antidepressants are slow-acting. It often takes several weeks to make a noticeable difference in how people with depression feel, says Kaplin. On the other hand, esketamine immediately impacts brain cells, offering relief from depressive symptoms within hours.