This article originally appeared on Tonic Netherlands.
We've known for a long time that ketamine could be a more effective treatment for depression than traditional antidepressants. American psychiatrists and scientists came to this conclusion in 2013, after they found out that the positive after effects of the drug lingered in the body a week after use, which wasn’t the case with regular antidepressants.
Now, Dutch researcher Jurriaan Strous wants to take things a step further with a new study in which he's hoping to find out if the drug can also help stop acute suicidal thoughts. Recently, Strous spoke at a gathering of Kleine Hans, a Dutch committee that specializes in child psychiatry. He talked about his research, which focuses on ketamine as a treatment method for acute suicidal tendencies.
Two months ago, Strous also finished up his training as a psychiatrist at teaching hospital Amsterdams Medisch Centrum (AMC) in the Dutch capital. He became intrigued by ketamine when he read an article about the drug as a treatment for depression. “At some point I heard that people were being treated with ketamine, but suspected this was quackery,” he says.
“Surprisingly, this article presented hard evidence. I was especially intrigued by the fact that [ketamine] works so quickly, and that the positive effect lingers even after the drug stops working.” In the Netherlands, some 100,000 people survive a suicide attempt on a yearly basis. Most of these people suffer from depression. A treatment method that kicks in right away is necessary for people who need immediate help, for instance after a failed suicide attempt or because they have strong suicidal thoughts. Ketamine would provide exactly that.
Strous’ research is financed by the Dutch foundation for health research and care innovation (ZonMW). The trial compares the effects of ketamine and Midazolam (a common anesthetic) on acute suicidal thoughts. Strous suspects that Midazolam doesn’t actually help when somebody is suicidal, though just like ketamine, it can make people groggy. “Some of the people who we’ve asked to participate in the study, we found in the emergency room of university hospitals in Leiden and Groningen after a failed suicide attempt,” says Strous. These people meet with a psychiatrist as soon as they are admitted, and he or she then asks the patient if they are interested in the trial treatment. “During most research projects about ketamine and depression, ketamine was administered through an IV. Because we need it to work even faster, we’ve decided on a nasal spray.”
During the trial, participants get a one-time dose of either ketamine and Midazolam, in order to determine if ketamine works adequately. “Later on, we want to figure out how we can reduce suicidal tendencies for a prolonged period. We don’t just monitor patients when they’re in the hospital, but continue to do so for over six months after they are discharged,” he says.
Based on previous trials, Strous knows that patients will soon start to feel better. Their personality doesn’t change and they won’t feel instantly happy, but the problem they were facing before will seem a bit less overwhelming. “It’s striking that ketamine doesn’t only have an instantaneous calming, paralyzing effect, but that this sensation doesn’t stop once the drug leaves the bloodstream. This indicates that something changes on a biological level,” he explains.
What's important to note, according to Strous, is how little research has been done about the side effects of ketamine. “We know about a few studies in China, where they use ketamine a lot. They did MRI scans and cognitive tests on people who used a lot of ketamine over a number of years—several grams a week. As a result you see big cognitive issues, in addition to problems with the liver and bladder. Even though our dosage isn’t nearly as high, we have no idea of knowing what the effects will be ten years from now.”
Strous also points out that there is a risk of abuse. Currently, ketamine abuse isn’t a problem in the Netherlands, but Strous says that we need to be very aware of possible addition issues, if the drug becomes a treatment option in the Netherlands.
Remko Koopman, a 43-year-old visual artist from the Dutch city of Leiden calls the drug "life changing." He was given ketamine for the first time last year, when he ended up in the hospital with a broken foot.
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“When I was already in the hospital, it turned out that they had to postpone the operation because the fracture was so severe. Due to the swelling [in my foot], they couldn’t operate safely. So I had to wait for a week. I was already feeling a bit down back then, but when I found myself in bed for days at a time, my mind really started spinning: How would I be able to make my living as a freelancer?” Remko became depressed and his condition didn’t improve. During a visit, a friend gave him a sketch book so he could distract himself, but it didn’t work.
“After my operation, I woke up with terrible pain. I was afraid something had gone wrong. The doctor told me that I responded to pain stimuli even during my actual surgery, and that the anesthesia possibly didn’t work as well because I drink alcohol. I was already using the maximum amount [of pain medication], so they had to come up with something else.”
The doctor suggested a minimal amount of ketamine, mixed in with morphine. Remko agreed immediately: “Anything to not feel this pain.” He was hooked up to an IV and was able to administer the drugs to himself through a special machine. The result was a dreamlike state, described by the artist himself as “living inside the womb.” “It was like I had access to a different world. It was a haze, and within it I felt like I was swimming in a sea of oil.”
People who use ketamine for party purposes snort between 20 and 30 milligrams in one night. The nasal spray Strous will be testing contains a surprisingly large amount: 75 milligrams. People might definitely feel something, he says. “Ketamine will work for about two hours. Some people might hallucinate slightly. Sounds could be perceived differently, as could shapes. Those are the so-called psychotomimetic side effects.”
Ketamine is hardly ever prescribed in the Netherlands. University hospital Leids Universitair Medisch Centrum (LUMC) in Leiden sometimes does, “but only when all other options have been exhausted,” Strous says. According to the current template for treating depression, patients first need to try five different antidepressants, psychotherapy, and electroshock therapy. “Using ketamine earlier on in that process might be easier on the patient.”
Remko was on his special IV for two weeks. He filled the previously disregarded sketch book with drawings. “The first drawings were these vague, floating shapes. As if you have a fever dream. Later on, they became more concrete and autobiographical, even. I made a drawing of myself in the sea of oil. I kept on drawing, even after I was discharged. Ultimately, I put all of my sketches together in a book called Door de dubbele deur ("Through the double door," in English).
Remko was never suicidal. He does believe that his experience with ketamine was able to cure his depression, because the effect of the drug lingered for weeks after he took it. “It’s very personal, you know. I still notice that when I talk about it. But I look back on it in a positive light. Because of ketamine, I started—and kept—drawing, and this allowed me to work through my trauma.”
Not everyone in the medical field is pro-ketamine. The pharmaceutical industry, for instance, has little interest in the drug because it’s not profitable, explains Strous. Researchers, psychiatrists and doctors have expressed doubts. “Many people don’t believe in it yet. On one hand they have a hard time dealing with change, especially when it comes to using illegal drugs. This is a taboo, of course. It goes against what people know and against their experience, and when it comes to that most people are conservative. On the other hand, clinical trials still have to prove how effective it is in the long term.”
“What matters right now is the effect size—how big of an effect ketamine has. Currently, we already know that it’s about thee to four times the size of regular antidepressants. This is why it has a lot of potential to relieve people with suicidal thoughts for a longer period of time. In the future, we will end up in a situation,” Strous says, “in which we have to ask ourselves if it’s ethical to not prescribe ketamine.
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