Can ketamine stop suicides? A neuroscientist’s perspective

Scott Thompson (University of Maryland, School of Medicine) discusses the current evidence for ketamine as a psychiatric treatment for severe depression, the unknown risks of long-term use and both the promises and risks of the newly approved esketamine nasal spray.

To learn more, check out our article, “Listening to ketamine.”

Video Transcript:

Scott Thompson (PhD and chair of physiology, University of Maryland): “It’s been a tough week. We’ve lost two of the teenagers that survived the Parkland school shooting. We lost the father of one of the Sandy Hook shooting victims.”

Since the 1980s, new drug development for depression has stagnated.

Scott Thompson: “Right now we have nothing to offer for patients with acute suicidal thinking. I run a laboratory that’s dedicated to understanding what goes wrong in the brains of people with depression and what we can do to treat the symptoms of depression. In my laboratory we use rats and mice to advance our studies.

“The standard of care for treating depression right now has been the selective serotonin reuptake inhibitors — Prozac. These drugs act slowly, six to eight weeks typically in patients before they begin to feel relief of their symptoms. That’s a huge problem.”

For some patients the wait for relief is life-threatening.

Eighteen years ago, a small dose of ketamine was administered to seven patients suffering with treatment-resistant depression.

Scott Thompson: “The finding that ketamine produced a rapid relief of depressive symptoms really revolutionized the field, revolutionized the way we think about the pathology of depression and also the treatment of depression. Ketamine is an anesthetic drug. If you bring your kid to the emergency room they’re very likely to get ketamine as an anesthetic. It also produces a mildly hallucinatory dissociative state, which has led to its branding as ‘Special K’ and its adoption in the rave culture, for example.

“The finding of the rapid antidepressant action of ketamine in 2000 was a bit of a surprise. What hasn’t gotten as much attention is the anti-suicidal action. Now we have a drug that acts within hours to relieve their suicidal thinking in a way that will have a persistent benefit after they leave the clinical setting. That is a fantastic ability that we did not have before now. This is revolutionary — it’s going to save thousands of lives.

“Why is it taking 19 years for ketamine to finally reach patients? One of the limitations is that the formulation that was available could only be administered through an intravenous drip. That’s a little bit of a nuisance. That’s not something that most psychiatrists would feel comfortable doing in their offices. Another factor that limited ketamine’s widespread adoption

was the fear of many people in psychiatry that these mildly hallucinatory side effects of ketamine would in fact trigger some psychosis-like state in patients who were repeatedly administered ketamine.”

Despite many unknowns, ketamine is finally going to market as an antidepressant.

Scott Thompson: “There’s been a lot of excitement in the last weeks because the FDA has now approved a nasally administered form of ketamine called esketamine. The nasal administration route has some pros and cons. The pros: It’s easy to administer. Every psychiatrist can do it in their doctor’s office. That’s great, that will increase availability, increase the likelihood that patients can benefit from its rapid antidepressant actions.

“Of course, the negative side of making it easily accessible and widespread is the risk for abuse. The same week that the FDA approved the use of ketamine, with its uncertain risk for addiction, an article was published by the American Medical Association that really established that although controls were put in place when fentanyl was made readily accessible — in the form of lollipops, for example — that those controls failed. Are we letting the same genie out of the bottle by creating a nasally administered form of esketamine? We don’t know.

“Everything we know about ketamine now has been from short administrations in defined periods of time. We really don’t know anything about chronic long-term ketamine use even in a clinical setting. Is it safe for the brain? Is it good for mental health? Are there people who are going to be susceptible to chronic administration of ketamine?”

Knowing all the risks, would a neuroscientist still use it?

Scott Thompson: “All the evidence that we know of now does indicate that ketamine is safe and effective. If I had a loved one with a severe acute incidence of depression or suicidal thinking, I do think that ketamine would be the drug of choice.”