Telehealth startups prescribing ketamine at home are stirring concern

Since the late ’90s, Kathy Wallace has been battling major depression with a series of drugs — first Prozac, then three others, and back again to Prozac. But in the last six months, nothing seemed to be helping. So her psychiatrist recommended something new: Spravato, a nasal spray approved in 2019 that delivers a drug similar to the hallucinogen ketamine.

When the 53-year-old researched nearby clinics, though, she found them out of reach. She’d need someone to drive her to and from the appointment, nearly an hour round-trip from her home in Orange County, Calif. She could have tried a clinic that offers off-label infusions of generic ketamine, which is approved as an anesthetic, to treat depression. Her psychiatrist wasn’t a fan of that option — and at nearly $1,000 out of pocket per infusion, neither was Wallace.

She soon found a third option online. For $500, a telehealth company called Peak could prescribe her five doses of generic ketamine lozenges and deliver them to her home. “For me, at-home seems to be something I can probably stick with and not too much of a stress,” said Wallace. She entered her credit card info, and late this summer, settled in at home for her first dose.

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Peak is one of at least a dozen companies that have recently started prescribing ketamine online, responding to a lucrative opportunity created by the loosening of telehealth regulations during the pandemic. Typically, federal law requires an in-person exam before a patient can get a controlled substance like ketamine online. But the public health emergency triggered an exception in the 2008 law establishing those guardrails, the Ryan Haight Act, sparking a new business model for Peak and competitors like Mindbloom, Nue Life, and Wondermed.

Collectively, they pitch ketamine as a breakthrough solution for everything from treatment-resistant depression and generalized anxiety disorder to more commonplace issues like “stress,” “feeling lost,” and “bad habits.” In ads that appear on Facebook, Instagram, and TikTok, they promise “fast relief and lasting transformation,” reassuring users that the approach is “proven safe, effective and affordable,” at $100 to $300 per ketamine session. “Feel completely normal,” reads an ad from Peak.

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But experts worry that those claims, and their companies’ practices, are rapidly outpacing the science. They see thousands of patients being drawn in by marketing that promises rapid improvements in a wide array of mental health disorders, without transparency into the low level of evidence behind the telehealth practices. And taking ketamine at home without appropriate medical supervision, some emphasize, could leave patients at risk.

“They’re doing something that’s dangerous and unproven,” said Michael Banov, a psychiatrist who administers IV ketamine in his Georgia clinic. “And it’s really trivializing the use of ketamine.”

Despite its reputation as a recreational drug, ketamine and its dissociative properties are being taken more seriously by many psychiatrists, as a growing body of research suggests the generic drug can be effective against treatment-resistant depression. Many clinicians embraced the approval of Spravato, or esketamine, which is chemically related to ketamine. But with clinic waitlists hundreds of patients long, “we cannot possibly meet the demand,” said Cristina Cusin, who co-directs a ketamine clinic at Massachusetts General Hospital. “I understand a patient getting frustrated and trying alternative ways to try to get [ketamine], some out of curiosity, some out of desperation.”

That demand, combined with the pandemic’s allowances for telehealth, drove venture capital investment in at-home ketamine startups, whose leaders often invoke tech companies to characterize their disruptive potential. “The technology that we now have allows us to Uber-ize medicine,” said Roger McIntyre, CEO of Braxia Scientific, which recently acquired at-home ketamine company KetaMD. Mindbloom closed an undisclosed Series B round last September, and Nue Life has brought in more than $25 million in funding.

“What we’re seeing right now, it really is a blue ocean market opportunity,” said Wondermed co-founder and managing director Jose Muñoz Aycart, invoking a business theory that emphasizes the value of new, untapped markets.

But at-home ketamine is so new, in fact, that, “it’s one of those cases where the technology is going faster than the scientific effort,” said Matteo Malgaroli, a digital mental health researcher at New York University who authored a paper with Mindbloom.

Patients may be reassured by websites touting the drug’s “safe and proven” effects, or statements like Nue Life’s claim that “ketamine has full FDA approval.” But patients STAT spoke with for this story weren’t aware that the generic ketamine being prescribed for their at-home use hasn’t been approved to treat any psychiatric disorder — only for anesthesia. And while studies have shown ketamine can be effective in treatment-resistant depression, there is less data to support its use for marketed conditions like anxiety and post-traumatic stress disorder.

There is also relatively little research into the effects of the sublingual form of ketamine typically prescribed by at-home companies and some psychiatrists, a form that the body metabolizes differently from either nasal sprays or intravenous delivery. Sublingual doses of 100 to 1,000 milligrams are typically scaled to a patient’s weight, and are far lower than those used for anesthesia. But how much of the drug is absorbed and used by the body is not as predictable as with intravenous infusions, said Yale psychiatrist Samuel Wilkinson, who has studied the off-label use of generic ketamine to treat psychiatric disorders. Among the still-small field of ketamine providers and researchers, many have financial relationships with Spravato maker Janssen, including Wilkinson, Banov, Cusin, and McIntyre.

Wilkinson added that “no one’s really studying this in a systematic way from a health care delivery perspective.” Research into the safety and efficacy of at-home delivery of ketamine — which involves combining new forms of online screening, remote monitoring during treatments, and follow-up, often with less direct time spent with licensed clinicians — is extremely limited.

In clinics, patients are typically monitored for spikes in blood pressure or dysphoric reactions that can occur in a small number of patients. But very few telehealth companies directly monitor patients during ketamine sessions, and even fewer use licensed providers to sit in virtually. More often, they require patients to take their own blood pressure before or during one or more treatments, have a trusted person present — sometimes requiring video or photographic proof — and call in for a wellness check after the treatment. Some have patients check in with a “guide,” who is usually not a licensed health care provider, to provide proof that they’re taking the intended dose.

“I was shocked with how little monitoring there was,” said Banov, who wrote about two of his patients’ experiences with at-home ketamine companies in a recent Psychiatric Times article. In addition to patient safety concerns, psychiatrists worry that prescription ketamine could be resold and used illegally, or that patients receiving multiple low-dose lozenges for use over time could take them all at once.

“I think a lot of people in this field are trying to crack the code of the balance of safety and also sustainability and making sure it’s accessible financially for people,” said Ben Medrano, Nue Life’s chief medical officer.

Both Nue Life and Mindbloom have recently published research into their approaches to at-home ketamine, concluding that they are safe and effective against anxiety and depression. But providers are unconvinced that the observational research backs up those assertions; in Mindbloom’s paper, for example, more than half of assessed patients were not included in follow-up analyses.

“At no point did Mindbloom say this is the last word on the subject,” said the company’s general counsel Michael Petegorsky. “This is the beginning of additional research that we plan to add to the body of knowledge supporting the efficacy and safety of at-home ketamine therapy.”

There are also questions of whether the patients getting the drug online are those who would stand to benefit most. Marketing language for some at-home ketamine companies emphasizes mental wellness more than treatment of distinct psychiatric disorders: “Find happiness with at-home ketamine therapy,” reads one ad from Choose Ketamine. And while most businesses claim to prescribe ketamine only for patients with depression, anxiety, and post-traumatic stress disorder, others can slip through: One patient of Banov’s who tried at-home ketamine “was not even using it for depression, he was using it really for mind-expanding experiences,” he said. A story from Rolling Stone recently reported that Peak providers wrote prescriptions for patients without depression diagnoses.

Appropriate prescription of ketamine also hinges on how companies screen people. Some tap into existing patient records and check controlled substances registries, while others rely on patients to report accurate medical histories, including potential disqualifiers like a history or psychosis, or uncontrolled high blood pressure. But with so many potential online providers, patients can learn how to game the system. One patient with a history of possible hallucinations who was disqualified by Nue Life later got a telehealth prescription through another provider.

“Ketamine via telehealth has been precarious,” said regulatory compliance lawyer Hilary Bricken, who advises multiple at-home ketamine companies. “To treat yourself remotely, I still think it’s very dicey, even for my most responsible clients.”

Psychiatrists told STAT they are enthusiastic about the potential for ketamine to support patients who have struggled to find relief from their major depression symptoms with existing drugs and therapies. But they agreed that it’s unclear how telehealth practices should balance the risks with the benefits — and feared what would happen to ketamine’s progress if a patient were seriously harmed at home.

“You can’t have a Ferrari in every garage,” said Cusin. “I wish we could, but it’s simply not feasible to have it both ways: wide access for everybody and a super, attention-to-detail luxury package. You have to figure out how to maximize the benefit. I don’t know how low you can go with the standards.”

That’s especially important to figure out as struggling patients seek a long-term solution for their pain. Psychiatrists emphasize the importance of therapy to make the most of ketamine’s potential — and help patients cope if it doesn’t bring relief. But most telehealth companies direct patients to work through the integration of their experience with journal pages to fill out on their own, or send them to sessions conducted in an online group and run by unlicensed “integration specialists.”

“We believe that patients have the ability to take care of their own routines, of changes, of habits,” said Wondermed’s Muñoz Aycart. Others might provide resources for patients to establish their own relationship with a therapist.

“You can have a really interesting ketamine experience and feel better for a couple of days, but if you don’t put the pieces together for why that experience was relieving to you or what you can change in your life in order to suffer less, then I think it’s going to be about as useful as taking an as-needed benzodiazepine,” said Ryan Henner, a psychiatrist at Beth Israel Deaconess Medical Center who provides esketamine therapy.

For all the growth in the last two years, the at-home ketamine industry could come crashing down before it has the chance to address those burning questions. Barring another extension, the public health emergency is set to expire on Jan. 11, 2023 — and with it, the flexibility to prescribe ketamine without an initial in-person consultation.

“A lot of these companies that are doing ketamine treatments via telehealth, they’re going to have to scramble to comply.”

Hilary Bricken, lawyer

“A lot of these companies that are doing ketamine treatments via telehealth, they’re going to have to scramble to comply depending on how the DEA reacts when the party is over,” said Bricken.

Some companies aren’t preparing to make changes to their business, hedging their bets that proposed rules could extend those allowances for certain controlled substances. The Drug Enforcement Administration could also complete a task that’s been on its docket for years: creating a vetted registry of telehealth providers who would be cleared to write virtual prescriptions without an in-person visit.

Others are already planning to partner with brick-and-mortar providers who can establish in-person care and follow up with telehealth prescriptions if no changes are made. “If they fail to pivot,” said Bricken, “someone is going to suffer some incredible enforcement.” Mindbloom has tapped former House energy and commerce chairman Greg Walden to lobby on its behalf to make telehealth-only prescribing permanent.

In the meantime, patients are left to make their own decisions about whether they’re comfortable with a virtual ketamine company’s screening, monitoring, and follow-up care.

When Wallace took her first ketamine dose from Peak this summer, the experience “wasn’t bad,” she said, though it didn’t meaningfully change her symptoms: “I sort of spaced out for a little while, felt kind of floaty.” She wasn’t clear on where to put the lozenge, which is meant to dissolve under her tongue; she ended up swallowing it and getting nauseated.

But when she didn’t hear back from Peak about her four follow-up doses, she started thinking about the interaction differently. In early September, a week after Rolling Stone published its story critical of the company’s practices, she finally got an email: Peak would be shutting down, citing the upcoming regulatory changes.

“Instead of holding out until the very last minute, we wanted to ensure patients have a safe transition period to titrate off medication or transfer to another clinic,” Peak said in an emailed statement.

Wallace was ultimately able to get her money back, but she was soured on the experience. “The way they did things seemed a little dangerous to me,” she said. Her clinical appointment to see if she was eligible for ketamine “didn’t really seem all that thorough.” Now, she’s trying again with Mindbloom, feeling more confident that her medical history was well-vetted.

And at the end of September, just as Peak stopped seeing patients, she received a package in the mail: It was her other four doses of ketamine.

This story has been updated with additional information about Janssen’s financial relationships with ketamine providers and researchers.

Source: STAT