There's new evidence that a 'party drug' is a rapid-fire treatment for depression
- Ketamine - used legally as an anesthetic and illegally in club settings - is emerging as a potential new treatment for some types of depression.
- A new study found that ketamine was better at curbing suicidal thoughts in depressed patients than a sedative.
- Researchers have called ketamine "the most important discovery in half a century."
- We visited a ketamine clinic that offers 45-minute infusions of the therapy in San Francisco.
After a 45-minute infusion of ketamine, clients at a clinic in San Francisco's Nob Hill neighborhood are not partying.
Instead, they're in a state of quiet contemplation - reclining on cushioned chairs, listening to music, or occasionally striking a tranquil yoga pose.
These clients are patients at one of ten ketamine clinics operated by Actify Neurotherapies, a network that offers the treatments to people diagnosed with severe forms of anxiety and depression. Ketamine is best known for its illegal recreational uses - it is a powerful dissociative that can induce feelings of being separated from one's own body. But it is also one of the safest and most widely used legal anesthetics. And ketamine's utility as an antidepressant has recently started to gain attention.
A new study out of Columbia University Medical Center found that ketamine worked significantly better at curbing suicidal thoughts in depressed patients than a commonly used sedative.
A spate of studies over the past several years have also suggested that ketamine may provide swift and powerful relief to people suffering from some of the hardest-to-treat forms of depression - an illness that is the leading disability worldwide. The findings have been so promising, in fact, that some researchers are calling it "the most important discovery in half a century," though other experts say more research is still needed.
The US Food and Drug Administration has not approved ketamine for the treatment of anxiety or depression, so clinics that offer it for these uses are doing so off-label. Actify Neurotherapies is one of an estimated 50 to 100 such clinics taking the same approach across the US.
The potential promise of ketamine
Actify Neurotherapies' San Francisco office is a cross between clinical and therapeutic. In each treatment room, a reclining clinical chair sits facing a large window. In the corner is a chair decorated with a colorful crocheted blanket.
"We're striking a balance between a clinical setting and a home setting," Steve Levine, a psychiatrist and the CEO of Actify Neurotherapies, told Business Insider.
Each two-hour visit includes 45 minutes of ketamine infusion, 45 minutes of a saline drip, and a consultation with Alison McInnes, a physician who founded a regional ketamine therapy program with Kaiser Permanente.
"Therapy and ketamine go together like peanut butter and chocolate," Levine said. "And with our approach, you have someone with an extensive background in mental health and therapy always present, and talk therapy happens before and after the infusion."
The latest research on ketamine's potential to treat depression - specifically the deadliest complication of the disorder, suicide - was published in December in the American Journal of Psychiatry. The Columbia University researchers found that ketamine did a significantly better job of curbing suicidal thoughts in depressed patients than a commonly prescribed sedative.
Current interventions for people who find themselves thinking of ending their lives are limited to hotlines, sedative drugs, and talk therapy, and 90% of people who die by suicide have a mental illness at the time of their deaths, according to the American Foundation for Suicide Prevention.
So for the latest study, researchers randomly assigned a group of 80 people with depression to either receive the sedative midazolam or ketamine.
Within 24 hours, the patients given ketamine had less suicidal thoughts than those who received the midazolam. They also had greater scores on tests designed to measure their mood and fatigue levels - benefits that, in some of the patients, lasted for more than a month.
That builds on findings from the first large, non-preliminary study of ketamine in people suffering from some of the hardest-to-treat forms of depression. For that study, which was published in the journal Scientific Reports in May, researchers at the University of California, San Diego used an FDA database of 8 million patients and found that those who'd been given ketamine for chronic pain reported symptoms of depression 50% less frequently than those who'd been given other combinations of pain drugs.
"This reduction in depression is specific to ketamine and is known to be much more rapid than current antidepressants," the researchers wrote in their paper, adding that their observations were "very promising" for people with serious depression or thoughts of suicide.
"These patients cannot afford to wait up to six weeks for reductions in their depressive symptoms," they wrote.
Developing ketamine treatments
These results have not gone unnoticed amongst pharmaceutical companies.
Johnson and Johnson is developing a form of ketamine that could be better tolerated and would be marketed as an antidepressant; Allergan is in the last phase of clinical trials with a drug that acts on the same receptor as ketamine.
Still, like any drug, ketamine may have its own risks and side effects. Some studies have suggested these could include kidney and blood pressure complications, for example. Plus, most studies on ketamine use in people with depression have been limited to about two weeks, so it remains unclear how long the benefits last.
Furthermore, such treatments often range from $400 to $1,000 per infusion around the US, a price tag that can leave vulnerable patients paying out of pocket and not getting reimbursed at all. A single infusion at Actify costs $650, and insurance doesn't officially cover any of that, but Levine said his team can typically get providers to reimburse "a lot of it."
For Levine, all those negatives pale in comparison to the host of downsides that can accompany most treatments for depression.
"When you're treating very very ill people, you will have side effects. That's a reality," Levine said, adding, "these are people who've been sick for decades and heard from multiple doctors that there's nothing else they can do. We're enabling them to get back to their normal lives."
Other treatments for depression, like talk therapy and antidepressants, mostly haven't improved since they were introduced in the 1950s. Decades of research suggest that those existing treatments don't work that well for everyone, and may not work at all for some. Yet physicians and psychiatrists have been doling out the same medications to clients for 70 years.
'Why the heck aren't we using this?'
At Actify, most patients receive 10 infusions over the course of 10 weeks - three in the first week, two in the second, and one infusion in the third, fourth, and fifth weeks. The last two infusions are spread between weeks seven and 10.
Levine opened the network's first treatment center in 2011 in Princeton, New Jersey, and the other nine followed between 2015 and 2017. At each facility, doctors track patient progress, and patients fill out a standard depression and anxiety questionnaire before each treatment and the following day. Each Actify clinic has a psychiatrist or mental health professional on staff, though not all clinics offering ketamine infusions do.
Levine said that when he first saw a study about ketamine's impact on people with severe depression, it "spun his head around."
A 2012 review of four preliminary studies in patients with severe depression concluded that approximately 65-70% of patients responded well to ketamine. The other 35-30% either did not have a significant response, or their relief from depression was only short-lived.
"The findings were unanticipated, especially the robustness and rapidity of benefit," the authors wrote in their review. "Ketamine appeared to directly target core depressive symptoms such as sad mood, suicidality, helplessness and worthlessness, rather than inducing a nonspecific mood-elevating effect."
Some scientists seeking a new approach to treating depression have also looked to psychedelics like ayahuasca and magic mushrooms, which appear to reduce depressive symptoms by increasing the connectivity between certain parts of the brain. So it's not a complete surprise that they're also exploring the depression-reducing qualities of ketamine, Levine said.
"Here's an incredibly safe medicine that works within hours," he said. "So my immediate question was, 'Why the heck aren't we using this?'"