What’s the Best Way to Use Ketamine for Depression?

Doctors say a nasal spray may not be the best way to administer a promising new depression drug

Illustration by George Wylesol

In March, the U.S. Food and Drug Administration (FDA) approved the first new drug for depression in decades, esketamine. The drug — which many experts are calling a groundbreaking new treatment — has the same molecular formula but different chemical structure as ketamine, also known as the illicit party drug, Special K.

Despite its reputation as a club drug, ketamine is increasingly used in medical clinics across the country for people with treatment-resistant depression (TRD), or those with clinical depression who have not been relieved of their symptoms through the use of other drugs or therapy. TRD affects one-third of the estimated 16.2 million Americans who have depression, and it carries a higher risk of suicide. Ketamine is known for acting fast and effectively, and an influential study in 2006 from the National Institute of Mental Health found that 18 people who used the drug reported a drastic shift in mood within hours.

Exactly how ketamine works as an antidepressant is unknown, but experts believe it could be that the drug increases the number of synapses, or connections, in the brain, which can be worn down by stress and depression. It’s…