Time to Ket rid of your depression

Ketamine, a hallucinogenic party drug known as Ket or K, can induce a dream-like, detached state and creates a chilled, happy mood in the user.

Medical ketamine, called esketamine, has been approved by the US Food and Drug Administration (FDA) as an antidepressant with extremely promising prospects.

The club drug may be the fastest-acting antidepressant ever, being able to lift a severe depressive mood in hours. Traditional antidepressants, such as SSRI’s like Prozac and Zoloft, take weeks to treat symptoms. Some patients report feeling better two hours after taking ketamine.

SSRI’s target the brain chemical serotonin, which eventually affects another known as the NMDA receptor. Ketamine skips the serotonin part and goes right to the NMDA receptor. Consequently, esketamine is the first antidepressant to operate on a new mechanism of action in decades.

“It was hard to have any emotions, because I was just numb,” said Robin P, an esketamine clinical trial patient. “When I began treatment with esketamine and my symptoms started to lift, I could see very clearly just how depressed I had been. I’m now able to appreciate a wider range of emotions than when I was depressed. My long-term goals have taken shape and actually seem attainable.”

Esketamine, developed by Janssen Pharmaceuticals, will be used to treat those suffering from treatment-resistant depression (TRD). This is diagnosed when those with major depressive disorder (MDD) fail to respond to two traditional antidepressants. Approximately one-third of US adults with MDD also have TRD.

Suicide is a much greater risk for those suffering from TRD. Due to its fast acting nature, esketamine has the potential to snuff out suicidal thoughts early into treatment. The drug must be taken in a clinic and the patient is then supervised for two hours.

“I’ve got a guy, he eventually got better on standard antidepressants. But it took three weeks; they were the worst three weeks of his life, and mine. That’s the sort of person I might give the esketamine spray, to buy time until the standard treatment works” said Dr. John Lauriello, chair of psychiatry at the University of Missouri School of Medicine, in Columbia to the New York Times.

A 2016 study of 14 found that half of the participants experiencing suicidal thoughts experienced relief after taking infusions of ketamine. These were patients suffering from TRD. Those that experienced relief reported no strong suicidal thoughts after three weeks.

Researchers think that the LHb, a small, central brain region, known as the “disappointment centre”, plays a role in depression and suicidal thoughts. When this centre activates in bursts, it inhibits the brain’s “reward centre”. Ketamine reverses this process.

“I frequently couldn’t even get out of bed,” said Liz Lehmann, a patient in the 2016 study. “There was no escaping it ever. It was all-encompassing. It touched every piece of my life … [Now] I feel wonderful. I feel energized, ready to hit my day.”

The data indicates that ketamine may work on depression in a number of ways. Alan Schatzberg, a psychiatrist at Stanford University in California, suggests that it may jump start the brain in some unknown way and then permanently rewire it by blocking NMDA receptors.

He also suggests that it works like morphine; rapidly binding to opioid receptors in the brain. He points to studies that suggest that it is the out-of-body experience that causes a change, indicating that it may even be ketamine’s recreational function that battles depression.

David Kelly

Image credit: Science News