Ketamine Inches Closer to FDA Approval To Treat Depression

If approved, esketamine would become the first new treatment for major depression in about 50 years.

Johnson & Johnson recently announced that the Food and Drug Administration (FDA) had given its experimental drug esketamine its second Breakthrough Therapy Designation. This means the FDA will expedite the research and review of the drug—bringing it closer to being approved as a new way to treat major depressive disorder (MDD) for those resistant to other treatments who are at high risk of suicide.

Esketamine is very similar to ketamine—also known as “Special K”—a Schedule III anesthetic that has become known as a "club drug" used recreationally for its ability to produce a dissociative state, as if detached from the body and physical surroundings. It is less commonly known as a date rape drug, given its ability to impair motor function and create a dream-like state.

Ketamine was originally approved in 1970 by the FDA and used during the Vietnam War as a sedative and anesthetic for wounded American soldiers. It continues to be used primarily for anesthesia. The U.S. placed it on its list of controlled substances in 1999. Some doctors already administer ketamine for the treatment of depression, by prescribing it off-label, since it is not currently approved to treat depression by the FDA.

The potential side effects are increased heart rate, nausea and risk of serious respiratory problems. If esketamine is approved by the FDA to treat MDD, it will be one of the first new ways to treat the disorder in the last 50 years.

The Fix spoke with neuroscientist Apryl Pooley for a clearer understanding of how ketamine will work for MDD, if approved.

“Ketamine has been studied for its antidepressant effects for years,” said Pooley. “Researchers at the National Institutes of Health found 10 years ago that injecting ketamine in depressed patients significantly improved their symptoms within two hours and the effect remained for a whole week.”

She explained, “This was huge because the standard antidepressant treatments can take weeks to even begin working, and then they stop working as soon as you stop taking them.” She did point out that the drug only works for 30% to 50% of depressed patients. On the upside, she said that ketamine has also been shown as a potential effective treatment for PTSD.

“Depression and stress can start to damage other systems in the body," said Pooley. "With depression, stress hormones are chronically elevated. Researchers found that this leads to shrinkage of brain cells.”

She added, “There is evidence that depression is associated with chronic inflammation. The inflammatory response works to get toxins out of your body, which is why bug bites flare up. The inflammatory response is working to get rid of those toxins. But, with chronic inflammation, it can actually start attacking your own healthy cells.”

Scientists believe that ketamine can help repair damaged brain cells. Some researchers have also suggested that ketamine can reverse or block tolerance to opioids, but they acknowledge that more research is needed.