By Tamarra Kemsley
Ketamine, an anesthetic infamous for abuse among club drug users, may actually help to alleviate even the most stubborn cases of depression.
It’s a hypothesis researchers have been testing for years, including as far back as 2006 when a group from the National Institute of Mental Health injected 17 patients with the drug. Those tested had tried an average of six treatments, all of which had failed.1
“These were very treatment-resistant patients,” Dr. Thomas Insel, director of NIMH, commented at the time. By the end of the day, 71 percent had responded to ketamine, roughly a third of which were nearly symptom free.2
A more recent study included 101 individuals, all of whom had been unable to find a therapy to that helped. Of this group, 42 responded to ketamine.3
“The first ketamine infusion literally saved my life,” one patient reported. “I had felt so desperate I was going to end it all.” Following a series of ketamine infusions, however, she was able to return to working full-time, something the patient says “has given me such a boost.”4
Part of ketamine’s allure is the speed at which it works. Whereas traditional therapies often take weeks and months to kick in, ketamine has been shown to alleviate symptoms in a matter of hours. For those struggling with suicidal depression, this kind of response time could mean the difference between life and death.
How It Works
Unlike traditional antidepressants designed to target the neurotransmitter serotonin, ketamine goes after glutamate, the chemical nerve cells use to send signals back and forth.5The drug limits the neurotransmitter that bridges the body and the conscious brain–a phenomenon believed to be at the root of the drug’s efficacy as an anesthetic. When it comes to depression specifically, research shows ketamine reduces the functional connectivity of a part of the brain that controls emotion, among other things. This observation has led researchers to hypothesize the drug essentially acts like a brake pedal for when this part of the brain starts spinning out of control with a person’s emotions in tow.6
Even as it reigns in certain processes, ketamine kickstarts others. According to animal studies, it induces growth in the parts of the neuron responsible for carrying electrical signals.
“Think of a neuron as a tree,” Dr. Rupert McShane, a consultant psychiatrist who leads the ketamine treatment program at Oxford Health NHS Foundation Trust (OHFT) in the United Kingdom, told the BBC. “In the winter of depression, things retract and our thinking is less rich. When spring comes, the tree buds. Ketamine stimulates the production of a nourishing fertilizer and budding.”7
The Risks
Nevertheless, many physicians remain skittish.
One reason is the size of the studies to date. As of March of this year, fewer than 400 individuals had taken the drug as part of a clinical trial.
“That’s pitifully small compared to what a clinical trial would generally be comprised of for FDA approval,” Dr. Charles Nemeroff, chairman of the department of psychiatry and behavioral sciences at the University of Miami Miller School of Medicine, told TIME.8
Then there is the problem of long-term effects, which remain unknown, as well as the potential for abuse. Both of these concerns are particularly relevant given the drug’s transient effects. For most people, the effects wear off in anywhere from a matter of days to a few weeks. As a result, regular IV infusions are required.
Still, for psychiatrists like Dr. Gerard Sanacora, these risks often feel less pressing than the ones presented by severe depression.
“If you have patients that are likely to seriously injure themselves or kill themselves within a short period of time, and they’ve tried the standard treatments, how do you not offer this treatment?” the Yale psychiatry professor told NPR.9
And he’s not alone. All told, more than 3,000 patients have been treated with ketamine across dozens of clinics in the United States and Canada.
Coming Down the Pipeline
Meanwhile, trials are currently underway for a sister drug developed by Johnson &Johnson known as esketamine. The nasal spray has already received two Breakthrough Therapy Designations from the FDA–one in 2013 for its effect on treatment-resistant depression and one in 2016 for those with imminent risk for suicide.10 In the case of the latter, the study included individuals who entered the emergency room because they were a threat to themselves. “They get admitted to the hospital for standard treatment plus or minus esketamine. And what we saw again, within days, a dramatic improvement in the mood of these patients and a decrease in suicide ideology,” Johnson & Johnson’s William Hait told reporters in May of last year.11
If approved, the drug would arguably represent the most revolutionary therapy for depression since Prozac.
As Dr. Jame Murrough of New York’s Mt. Sinai Hospital told NPR: “This is probably the most interesting and exciting new development that I’ve seen in my career, and probably going back over the past 50 to 60 years.”12
1 http://news.bbc.co.uk/2/hi/health/5253800.stm
2 Ibid.
3 http://www.bbc.com/news/health-39501566
4 Ibid.
5 http://www.sciencedirect.com/science/article/pii/S0165178114008610
6 http://www.rollingstone.com/culture/features/ketamine-future-of-depression-treatment-w488998
7 Ibid.
8 http://time.com/4687244/ketamine-club-drug-depression/
11 Ibid.