From the start of the first lockdowns, people knew the COVID-19 pandemic would be devastating to people’s mental health. The CDC found that from August 2020 to February 2021, the number of Americans reporting symptoms of anxiety or depression increased from 36.4 percent to 41.5 percent. That included 57 percent of adults aged 18–29. Just as rates of depression are on the rise, so is the scramble to find solutions that could help provide relief to millions of Americans. More doctors and patients are pinning their hopes on a relative newcomer to psychiatric treatment: ketamine therapy.
In 2022, ketamine wears many hats. It’s a useful anesthetic; a scandalous club drug; and now a form of fast-acting therapy for depression, particularly when other treatments have shown limited to no success. The FDA approved the drug in a nasal spray form called Spravato in March 2019, and allows off-label prescribing of the drug.
The actual science of ketamine therapy adds up. After the resurgence of research interest in psychedelic drugs (previously abandoned to illegal recreational use in the 1970s), substances like psilocybin, MDMA, LSD, and ketamine finally received the research, funding, and credibility denied for decades.
As a drug “experience,” ketamine produces a dissociative state, allowing the depressed- or anxiety-ridden patient to feel relief from depression symptoms. Although it doesn’t usually produce the typical psychedelic hallucinations and effects as a drug like psilocybin, under a controlled setting and precise dosage ketamine can encourage similar insights. Severely depressed patients often feel relief after the first session.
Adam Kaplin, a neuropsychiatrist at Johns Hopkins University and the chief scientific officer of MyMD Pharmaceuticals, knows this research firsthand. He worked with drug company Janssen Pharmaceuticals to develop Spravato and he’s seen impressive results from supervised ketamine therapy.
“Even after four different trials of different antidepressants, only 60 percent of people have a response to the treatment, which means that there’s about 40 percent of people who don’t respond,” Kaplin told The Daily Beast. “There’s been a huge need for something, and not just something, but a huge need for something new, because we’ve been using the same me-too antidepressants from the 1950s.”
It turns out ketamine filled a much needed treatment gap. “We also needed something that worked quickly. This treatment works in hours to days,” Kaplin said.
This speed is a godsend for desperately depressed people. It’s exciting enough that a rash of ketamine therapy clinics opened up across the country in the last few years (there’s been an underground ketamine treatment network for longer than that). Because the drug can be prescribed by doctors off label, it’s being used for other mental health problems, such as anxiety. And now, since the pandemic, you can even get the therapy online, with the ketamine delivered to your door.
Access in 2022 might be fast and convenient, but it’s also unregulated. Bradley Kramer, a trained physician and lawyer who specializes in catastrophic medical liability at the firm Biklaw Trial Attorneys, likened the current ketamine therapy environment to “the wild, wild West.”
Ketamine Therapy Is Best Under Supervision
Until recently (and still in most cases), ketamine was only administered under very controlled conditions. Patients had to be deemed eligible — meaning they were diagnosed with a treatment-resistant form of depression. They had to have tried at least three rounds of antidepressants (usually SSRIs).
If they passed those requirements, those patients could move on to ketamine. This would be administered intravenously in a hospital setting, under supervision by a doctor or a sitter who could provide support in case emotions run high or anxiety peaked. Afterwards, the session would be thoroughly discussed with a therapist. There would also be a limit on the number of sessions allowed.
The approval of Spravato to treat treatment-resistant depression (TRD) and major depressive disorder has done little to change most of these requirements. It has to be used in conjunction with an oral antidepressant, such as an SSRI. Even though it’s in a convenient nasal spray, it can only be administered in a certified medical setting overseen by health professionals, with a two-hour wait afterward before they can leave the office, a precaution against any potential side effects or negative reactions. All of this, explained Reina Benabou, VP and head of medical affairs at Janssen Neuroscience U.S., falls under a framework called the Spravato Risk Mitigation and Evaluation Strategy (REMS).
These regulations can be really time-consuming for patients, but they also offer control and safety. And they haven’t slowed Spravato’s rise in popularity. Benabou said there are more than 1,200 REMS-certified sites around the country, with more than 396,000 treatments administered so far, and 18,000 patients treated.
Another option is for patients to simply go to a brick-and-mortar ketamine clinic that will prescribe the drug off-label and administer it intravenously under supervision — similar to a hospital visit, but at a site that’s dedicated to ketamine therapy. These are popping up more and more in urban areas over the last few years. The follow-up therapy sessions run with a mental health professional, however, may vary widely from clinic to clinic. Ketamine was originally conceived as part of a long-term treatment plan (and not a cure), aftercare is often touted as equally important. A potentially illuminating drug experience requires interpretation — otherwise it’s just another trip.
Like REMS sites, ketamine clinics are poised to grow fast this decade. Novamind, which owns a Utah-based chain of clinics under the name Cedar Psychiatry, told Forbes in October 2021 that it was seeing two-week wait times at each of its six clinics. It’s expecting to see 65,000 patients in 2022 — a 225 percent increase from last year.
Still, there’s no specific regulatory roadmap in place for ketamine clinics — which is one of the things that concerns both the doctor and the attorney in Kramer.
“The regulations are trailing very much behind these new facilities and management of certain conditions, so they’re operating basically independently,” Kramer said. “My concern is that you’re going to have patients who are going to develop severe reactions or have complications. Or, in the case of sending the medication to the patient’s home, not taking the medication correctly: taking too much, too little, having terrible side effects or death — god forbid. There’s no one there to take care of the patient. It’s bad enough if these patients have complications if they’re in a facility that has oversight. Talk about giving these things to patients with no oversight, that’s just a recipe for disaster.”
The most important factor, though, is having a sitter there just in case something goes awry. A former ketamine therapy patient and current ketamine session sitter who identified himself as Fergus spoke to The Daily Beast about his experience (he declined to give his last name due to concerns about his job security). He said he felt his role as a connector between the patient and the therapist is absolutely vital to the process.
“For some people, the idea of not having connections to body and self is so disorienting that it becomes psychological trauma,” he said. “And that’s why you want to have somebody there, so when it becomes overwhelming, you have an anchor. In my role as a sitter, I’m part of the container. It’s not me doing the therapy with the person, I’m there so that as things get out of control, I can say, ‘OK, let’s return you to your breath.’”
Kaplin, who has witnessed many sessions, stressed that patients display a very wide range of responses to the drug.“I’ve seen people have really frightening effects from it,” he said. “And the majority of people, I’d say certainly 60 percent at least, need to be talked through on the first and second doses. I had one guy who was so distressed that he just beat his hands against the floor and was just in a horrible negative space, and we had to really talk him down.”
Ketamine Therapy On Your Couch
While these practitioners feel in person supervision is essential, there’s a third option to ketamine therapy that has gotten a supercharged boost during the rise of telehealth during covid: remote therapy, which lacks an in person sitter at your session entirely. Startups like Mindbloom and My Ketamine Home do initial screenings of simple mental health questions and residential eligibility before signing clients up for mail delivery of six ketamine lozenges. Patients take the lozenges themselves, at home, and then discuss the experience with an assigned virtual therapist afterward.
Ketamine has one complication that can post a big problem to remote therapy: dosage is tricky to figure out. It took a fair amount of work in clinical studies to ascertain the intravenous dosage that works for most people. And ketamine dosage changes dramatically if it’s not intravenous or intranasal. Oral ketamine must be metabolized through the liver, and thus the dosage must be higher.
This is exacerbated by the fact that the antidepressant effect of ketamine only works in a limited window. “We know that this treatment with ketamine is biphasic — meaning a low dose does nothing, then you get into the sweet spot [as] it goes up and you’re in that Goldilocks range where you get a full antidepressant response,” said Kaplin. “But as you increase the dose more, the response goes down and you lose it. It has to be just right — not too low, not too high.”
That includes the speed at which ketamine enters the bloodstream. Lozenges dissolve slowly in the mouth over 20 minutes — Fergus described the taste as “crushed up aspirin and Drano” — so the odds of a patient trying to binge on them is probably low. While this can prevent an overdose or a misuse of the drug, it can also blunt how much relief a patient can get out of the drug.
“When you give an IV [of ketamine], you have to give it over 40 minutes to have an effect,” said Kaplin. “The chance of someone hitting that with an oral lozenge, just with the drug infused into it by a compounding pharmacy, is remote.”
Outside of dosage concerns, Kaplin is also adamant that supervision is essential. “This [remote therapy] is potentially putting patients at risk,” he said. “You’re better off going and getting an IV from a clinic that can do that.”
Fergus, while completely supportive of remote therapy, isn’t sure it’s being marketed responsibly, calling it “very cavalier.” Mindbloom’s online advertising, for instance, features quotes about ketamine therapy that are general and not specific to the remote route. There may be a big difference between an in person, guided session and one done potentially alone. And, as set and setting are so important for psychedelics, results might vary wildly.
But, Fergus does think that normalizing ketamine therapy, and giving therapists a chance to work with it, is a good idea. When he did his sitter training, he said about a third of the people there were psychiatrists, and they were already prescribing the drug. Companies like Mindbloom could operate as a pairing company for interested patients and ketamine trained psychiatrists, if there were enough of them to fulfill demand.
Remote ketamine therapy, however, might simply have arrived too fast, too soon.
“Within the psychedelic community, Mindbloom isn’t taken very seriously,” said Fergus. “These are the people not playing by the agreed upon rules of not repeating the mistakes of Tim Leary,” referring to the famed psychologist’s “turn on, tune in, drop out” message that seemingly destroyed the credibility of psychedelic therapy for decades.
Ketamine therapy is still young in 2022, but there’s no question it is growing fast. And yet, related issues around medical liability are still in their infancy. Such cases, while not manifesting in courtrooms yet, are probably coming. “I actually had a call two weeks ago about a guy who went to a ketamine clinic, and then 30 days later killed himself,” Kramer said. “Can you blame the ketamine clinic for that? I don’t know. I don’t think there’s been any real oversight as to what they can and can’t do. Because it’s such a new therapy, there’s very few litigations that relate to it.”
So while the ketamine business is poised to boom in 2022, it remains a wild, wild West — risks and all.
This content was originally published here.