A study led by Massachusetts General Hospital (MGH) investigators identifies two subanesthetic dosage levels of the anesthetic drug ketamine that appear to provide significant symptom relief to patients with treatment-resistant depression. In the October 2018 issue of Molecular Psychiatry they describe finding that single intravenous doses of 0.5 mg/kg and 1.0 mg/kg were more effective than an active placebo in reducing depression symptoms over a three-day period. Two lower dosage levels that were tested did not provide significant symptom relief, although some improvement was noted with the lowest 0.1 mg/kg dose.

“Treatment resistance in depression is a major issue, with more than half of patients not responding adequately to standard, appropriate antidepressant treatment,” says Maurizio Fava, MD, executive director of the Clinical Trials Network & Institute in the MGH Department of Psychiatry and senior author of the Molecular Psychiatry paper. “There are only a few approved therapies that can help some patients with treatment-resistant depression, so we critically need more options to choose from.”

Long used as a general anesthetic drug, ketamine has been found in several studies to rapidly relieve depression symptoms when given at low, subanesthetic doses. Most of those studies used a standard 0.5 mg/kg intravenous dose, leaving determination of the optimal dosage unclear. To investigate that question, the study tested four different ketamine dosages – 0.1 mg/kg, 0.2 mg/kg, 0.5 mg/kg and 1.0 mg/kg – compared with an “active” placebo, a drug that induces side effects, the lack of which could lead participants to realize they are not receiving the medication being tested, potentially biasing their perception of symptom improvement.

The study enrolled 99 adults with treatment-resistant depression at six research centers – MGH, Baylor College of Medicine/Debakey VA Medical Center, Icahn School of Medicine at Mt. Sinai, Stanford University School of Medicine, University of Texas/Southwestern Medical Center, and Yale University. Participants were randomized into five groups – the four dosage levels and the active control group, with neither they nor the research staff aware of group assignments – and continued taking their previously prescribed antidepressants during the study period.

Participants were assessed with a standard depression rating scale the day they received the infusion and 2, 3, 5, 7, 14 and 30 days later. Additional instruments measured aspects of mood and suicidal thought. Dissociative symptoms such as memory loss and feelings of detachment from reality were assessed during and after ketamine infusion, and vital signs were measured after treatment and at all follow-up visits.

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On the standard depression scale, participants receiving ketamine had significantly greater symptom improvement during the three days after infusion than did those in the active control group. Comparison of dosage levels, after adjusting for multiple comparisons, found statistically significant improvement compared to the control group only for participants receiving 0.5 mg/kg and 1.0 mg/kg doses. The low 0.1 mg/kg dose produced significant relief only prior to adjustment, and the 0.2 mg/kg dose did not show any significant benefits. It is possible that the lack of efficacy at the 0.2 mg/kg level could reflect the small size of treatment groups and the fact that participants in that group tended to be more treatment resistant to begin with, the authors note.

For most participants in the higher-dose groups, the benefits of ketamine treatment began to decrease on the third day after treatment and were no longer detectable after five days. There were no significant differences in the occurrence of adverse events among all study participants.

Co-author Cristina Cusin, MD, who directs the MGH Psychiatry ketamine clinic, says “These results support the clinical observation that one size – in this case the most studied dose of 0.5 mg/kg – does not fit all, as some patients may require a lower-than-average dose; and each patient needs a tailored treatment plan that may include ketamine, together with other medications and talk therapy. We still do not understand which factors play a role in determining lack of response to treatments or which is the best possible strategy for patients suffering from severe depression.”

Fava, the Slater Family Professor of Psychiatry at Harvard Medical School, adds, “Along with supporting the efficacy of intravenous ketamine for patients with treatment-resistant depression, our study also suggests that even lower doses may be effective in some patients. Further investigation should examine the efficacy of repeat doses of ketamine, as well as whether higher doses may require less frequent administration.”

[Read the Original Article]

By MEGAN THIELKING @meggophone

OCTOBER 11, 2018

As ketamine clinics pop up across the U.S. to offer experimental infusions for depression, anxiety, and a slew of other conditions, training programs to teach providers how to run these businesses have also started to appear. They promise to teach everyone from anesthesiologists to advanced practice nurses the ins and outs of ketamine, which has been used for decades as an anesthetic but is still under study as a therapy for psychiatric disorders.

The doctors and nurse anesthetists offering the courses say they’re urgently needed to try to bring some standardization to the booming ketamine treatment business. “I think [ketamine] is going to get wider spread use in one capacity or another. I’d like to see that be done appropriately,” said Dr. Gerald Grass, an anesthesiologist who runs the Ketamine Institute, a training program run out of the Sarasota, Fla., practice where he also treats patients with ketamine. But some mental health experts say there isn’t yet enough evidence about how to use ketamine to offer training. They fear some of those signing up for the programs might be trying to break into the business to make a quick buck.

“If I thought there was a standard protocol … then I think [training] could be very useful. But I’m not sure we have that yet,” said Dr. Gerard Sanacora, a psychiatrist, professor, and the director of the Yale Depression Research Program. “There is a real limited amount of data. It’s ethically a challenging and clinically a challenging situation.”

Sanacora said he understands, however, the growing interest in ketamine: Many patients who haven’t benefited from conventional depression treatments are in desperate need of relief.Related: Do you have an experience with ketamine treatment? Share your story with us

Studies suggest that the drug holds potential as a treatment for major depression in some — though nowhere near all — patients. A dose much smaller than what’s used for anesthesia, given through an IV, stems symptoms of severe depression in some patients with treatment-resistant depression, often within hours.

But there are gaping holes in the data on long-term effects of ketamine, potential risks down the road, and the best way to integrate the drug into a broader mental health care plan.

A STAT investigation published last month found wide-ranging inconsistencies among clinics. Some clinics don’t thoroughly screen patients, and experts worry they’re offering the drug to anyone who can afford it. Providers charge anywhere from $350 to close to $1,000 per infusion and many patients get at least six rounds of the treatment. Some clinics, too, offer ketamine for uses that haven’t been well-studied, overhype its efficacy, and tout special blends that experts say aren’t supported by published evidence.

The Ketamine Institute offers two classes. The first, a $4,950 fundamentals course, is “directed to physicians who wish to quickly get the basic training necessary to [safely] and effectively provide ketamine infusion therapy to their patients,” according to the institute’s website. Grass said that course is targeted at providers who might want more information on the research and clinical care, but are familiar with starting IVs. The second, an $8,950 comprehensive course, takes a much deeper dive into the weeds of running a clinic and also gives physicians hands-on experience with patients.Related: Ketamine gives hope to patients with severe depression. But some clinics stray from the science and hype its benefits

Grass said he gets eight to 10 inquiries about the training courses each month. The number of people he’s actually trained: seven. He generally only trains psychiatrists and anesthesiologists and requires applicants to submit a statement about their intentions.

“There are people out there that are looking for alternate streams of revenue,” he said.

He gets inquiries from everyone from cosmetic dermatologists and chiropractors to venture capitalists. He even heard from a provider who was running an alternative weight loss program and wanted to add ketamine “to motivate his patients,” Grass said.

“People will read one or two research papers, see the protocol, and think, ‘Oh, my God, this is easy. I can do this in my office,’” Grass said.

To train under Grass, providers can spend several days shadowing at his clinic. Dr. Ricardo Febres Landauro, a psychiatrist in Austria, flew thousands of miles to take a course in January. He observed patient interactions, pored over his own cases with Grass, and left with a binder stuffed with information on ketamine’s effects, indications, and contraindications.

“After [training] with him, I felt confident,” Landauro said, adding that the course “was a magnificent experience.”STAT Plus: Access to exclusive, in-depth pharma, biotech, business and policy coverage. Join now.

Grass said he trains providers using the evidence in consensus statements published by the American Psychiatric Association and the American Society of Anesthesiologists. In his own practice, however, he deviates in some instances from published research and treatment protocols. He offers a proprietary product called the “Restore Ultra-Rapid Infusion,” which includes three treatments in three days and which the clinic claims lasts longer and is more effective than other ketamine infusions. His clinic promotes the infusions to treat anxiety, depression, PTSD, and “burnout syndrome.” Grass said physicians just starting to use ketamine might not be experienced enough to deviate from the standard.

“It behooves them to learn how to do the standard protocol effectively and safely,” he said.

Another training program, Colorado-based Ketamine Consulting, promotes on its website “turnkey, comprehensive services that propel clients towards success” in establishing their own ketamine clinics. It promises clients will come away with a “profit-generating ketamine clinic, a renewed love of medicine, and the independence that all physicians crave.”

That program is led by Dr. Roman Langston, an anesthesiologist who also provides ketamine to patients at his Denver clinic. Langston said he taps into his own background to give guidance on treatment, but Ketamine Consulting also serves as a one-stop shop for the business side of a clinic. It builds a client’s website, brainstorms branding, creates logos, and sets up a presence on Facebook, Twitter, and LinkedIn. He charges $1,500 a month for a six-month contract.NEWSLETTERS

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Providers are keen on the idea of formal training and a helping hand in launching their clinics. Since starting his consulting practice in summer 2017, Langston has had about 10 clients. Jason Duprat, who runs an online training program called the Ketamine Academy, said roughly 100 people have signed up for the course in just over a year.

“One of my goals was to increase the number of providers,” he said.

The cost of his program: $2,499 upfront, or three payments of $999. Like the Ketamine Institute, Duprat’s online tutorials cover the evidence on treatment protocols and contraindications when using ketamine. His course also emphasizes the business aspects, from the paperwork to set up your own private practice to the best ways to design a website.

“Some of the most common questions are on the business side of things,” Duprat said. The bulk of his clients are nurse anesthetists, like him, or nurse practitioners, Duprat said. That means they don’t necessarily have the know-how to get a clinic off the ground.Related: Companies are racing to develop fast-acting depression drugs — but the process is tricky

Christy Hatcher, a certified registered nurse anesthetist and advanced practice nurse in Minnesota, found that material particularly useful, along with the information on patient care. She signed up for the Ketamine Academy when she was starting the process of opening a clinic in Maple Grove, Minn. She had spent 17 years working in a Minnesota hospital when she decided to open a ketamine practice with another CRNA. They bought the course earlier this year as an “investment” in their clinic.

“It took a lot of the information that is out there and it put it all together for you,” she said. It also led them to bring a mental health nurse practitioner on board.

Their clinic will open in early November. Patients are already calling for appointments.

[Read the Original Article Here]

Walk into Kalypso Wellness Centers in San Antonio, Texas, and you might be treated with one of five “proprietary blends” of ketamine. They’re not cheap — $495 per infusion — and not covered by insurance, but the company offers a “monthly” membership program to cut costs and advertises discounts for members of the military and first responders.

Kalypso promotes ketamine, long used as an anesthetic during surgery and more recently as a club drug, as a treatment for more than two dozen conditions, including depression, chronic pain, and migraines. “Congratulations on resetting your life!!!” it cheerily tells patients on a form they’re handed after an infusion.

Starting with just one office 19 months ago, Kalypso has expanded rapidly to meet surging patient demand for ketamine and now oversees two other Texas clinics and offices in North Carolina and New York. It recruits customers through online ads and radio spots, and even by visiting support groups for pain patients, people with depression, first responders, and grieving parents who have lost children.

“You name it, we’ve done it,” said clinic co-founder and anesthesiologist Dr. Bryan Clifton.

An investigation by STAT shows that Kalypso’s sweeping claims are hardly uncommon in the booming ketamine treatment business. Dozens of free-standing clinics have opened across the U.S. in recent years to provide the drug to patients who are desperate for an effective therapy and hopeful ketamine can help. But the investigation found wide-ranging inconsistencies among clinics, from the screening of patients to the dose and frequency of infusions to the coordination with patients’ mental health providers. A number of clinics stray from recommendations issued last year by the American Psychiatric Association.

STAT interviewed ketamine clinic owners, psychiatrists, and patients and reviewed online staff pages and screening protocols for dozens of ketamine clinics to gauge how patients are selected and treated. Among the findings:

• Some clinics don’t thoroughly screen patients, and experts worry they’re offering the drug to anyone who can afford it. Clinics can charge anywhere from $350 to close to $1,000 per infusion and many patients get at least six rounds of the treatment.
• In many cases, clinics don’t have a psychiatrist or other mental health professional on staff, though they are working with challenging patients who haven’t responded to other treatments and may have suicidal thoughts. And not all clinics collaborate closely with a patient’s own mental health provider or even require patients to have one throughout treatment.
• Clinics sometimes overhype the efficacy of ketamine, offer it for uses that haven’t been well-studied, and tout special blends that experts say aren’t supported by published evidence.

Patients are “getting treatments they may not need or that don’t work, or they’re getting more than they needed,” said Dr. Jeffrey Lieberman, psychiatrist-in-chief of Columbia University Medical Center. One of the biggest risks from the explosion in ketamine use, he added, is “people getting fleeced.”

Clifton said Kalypso works closely with referring physicians or mental health providers and makes sure that anyone who seeks treatment for suicidal thoughts “has adequate mental health care.” Other clinics told STAT that they try to work with a patient’s mental health provider or another physician.

There’s a clear need for new treatments for major depressive disorder, and experts agree that ketamine holds potential to rapidly treat depression and possibly other mental health conditions in some — though nowhere near all — patients. Drug companies are testing similar medications for depression, suicidality, and bipolar disorder, but it hasn’t yet been approved for these conditions.

That fact hasn’t diminished patients’ desire to try ketamine. Actify Neurotherapies, which oversees 10 clinics that provide the drug, said it has received nearly 28,000 inquiries through a call center or online request form — just since January.

“Ketamine has become this phenomenon,” said Lieberman. Continual media coverage has fueled the excitement, generating significant interest and optimism among patients and physicians alike.

Mental health specialists don’t begrudge providers for opening their doors and offering a potentially beneficial treatment to patients eager for relief before it’s approved by the Food and Drug Administration. But they say some clinics are going too far in their promises — and not caring appropriately for patients.

“This is not snake oil. It’s not something that has to be stamped out,” Lieberman said. “It’s something that has to be reined in.”

Seeing hope in an experimental therapy

Rory Basurto knows the date of his first ketamine treatment by heart: Oct. 17, 2017. For more than a decade, he had suffered from devastating depression and thick anxiety that felt “like walking around with a wet blanket on all the time.” The 36-year-old can rattle off a laundry list of treatments he’s tried: Paxil, Lexapro, Zoloft, Ritalin, klonopin, neurofeedback, psychotherapy.

“It helped until it didn’t. Until I completely broke down,” said Basurto, who lives in Encinitas, Calif. That was last fall, when he had to quit his job working with a family business and attempted suicide.

Basurto, like many patients contending with major depression, needed another option. Many don’t respond to conventional antidepressants, such as the SSRIs. And for others, the drugs just don’t work quickly enough, taking weeks to kick in.

“Patients are getting more and more frustrated because the help that they’re getting failed them,” said Dr. Lori Calabrese, a psychiatrist who treats patients with ketamine at her clinic in South Windsor, Conn.

Ketamine has started to fill that breach. Since the early 2000s, small studies have suggested that it might have potential as a depression drug. Unlike traditional antidepressants that target the brain’s serotonin and noradrenaline systems, ketamine appears to block a receptor called NMDA, which is activated by the neurotransmitter glutamate.

The evidence is promising: A dose much smaller than what’s used for anesthesia — given through an IV — stems symptoms of severe depression in some patients with treatment-resistant depression, often within hours.

In Basurto’s case, he read about ketamine online after his suicide attempt. He reached out to South Coast TMS and Ketamine, an Encinitas clinic opened in 2016 by Dr. Drew Belnap, an anesthesiologist. Belnap consulted with Basurto’s therapist, who confirmed Basurto has anxiety and depression.

Since October, Basurto has undergone nearly two dozen ketamine infusions, paying between $450 and $500 per treatment. About once a month, he heads into the clinic, fills out a questionnaire about his symptoms, and settles into a zero-gravity chair. A staff member monitors Basurto as the ketamine drips into his bloodstream. He watches nature videos on a TV during the roughly 50-minute treatment.

He said the drug has changed how he grapples with the everyday challenges that used to knock the wind out of him, often leaving him sad or angry.

“Before, something happened and it was the end of the world. I still go through that, but it’s a lot quicker now,” he said.

Drug companies are racing to create a rapid-acting antidepressant that can produce effects similar to ketamine. Janssen, a division of Johnson & Johnson, is testing a nasal spray of esketamine, a ketamine-derived drug. When combined with an oral antidepressant, it has shown promise in quickly curbing symptoms of serious depression, and is also being tested in patients at risk of suicide. Allergan is developing its own experimental rapid-acting antidepressant, rapastinel. Like ketamine, it works on the NMDA receptor, which is involved in learning and memory.

But there are clear limitations to the data on ketamine. There aren’t data on long-term effects or potential risks down the road. There’s no clear consensus between the providers currently offering it on optimal dosing, how to go about maintaining the drug’s effects, or the best kind of care to complement ketamine treatment, such as cognitive behavioral therapy.

“The pace of ketamine treatment in real-world practices has outstripped what researchers are able to do and publish,” Calabrese said.

Seeing an “urgent need for some guidance,” an American Psychiatric Association task force issued a consensus statement in April 2017 that laid out the medical evidence on ketamine, the kind of training it thought physicians should have, and advice for thoroughly screening patients. Because ketamine can possibly affect heart rate or blood pressure in some patients, it recommended clinicians who provide treatment have advanced cardiac life support certification.

The panel said the screening process for every single patient should include a comprehensive diagnostic assessment, an in-depth look at a patient’s history of depression treatments, a careful review of medical and psychiatric records, and a clear informed consent process that walks a patient through the risks and limitations of ketamine treatment.

It’s clear that some clinics aren’t sticking to those suggestions.

Minimal screening and untrained providers

Screening practices and the extent of collaboration with mental health providers vary wildly from one ketamine clinic to the next. That means some patients might not get the support they need, particularly if they don’t respond to ketamine, experts said.

At Actify Neurotherapies, people first talk to a “patient care coordinator” who asks a few questions to make sure there aren’t any big red flags, like psychosis. “It’s intended to be a sieve with large holes,” said the CEO, Dr. Steven Levine. A patient then has a consultation with a psychiatrist on staff.

At Calabrese’s clinic, she requests records from each patient’s psychiatrist and primary care doctor, then does a lengthy intake. But at other clinics, the intake process is quicker and leans heavily on a screening tool such as the PHQ-9 questionnaire, which is commonly used to diagnose symptoms of depression. That’s fueled concern that any patient who can fork over hundreds of dollars for each infusion might be offered ketamine treatment, whether or not it’s the right course of action.

“Where is the bar where they determine a patient is not appropriate for ketamine treatment if they can pay?” said Dr. Cristina Cusin, co-director of a ketamine clinic at Massachusetts General Hospital. Cusin, who is also a psychiatry professor at Harvard Medical School, has run several studies on ketamine for treatment-resistant mood disorders.

One patient, a 28-year-old graduate student in California who didn’t want to be named out of concern being identified could affect her job hunt, told STAT said that since the start of this year, she has seen four different ketamine providers. All agreed to treat her with the drug for her severe depression, anxiety, and panic attacks, even though her response to the treatment varied and it didn’t always help.

Experts also express concern about the coordination of care between clinics and a patient’s usual providers. Some clinics say they’ll work with a patient’s mental health provider if he or she wants them to do so. Levine said each of Actify’s clinics “engages the person’s outside primary team” throughout the course of treatment. At Kalypso, co-founder Clifton said staff follow up with a referring provider if there is one or will work with a patient’s primary care provider unless the patient specifically requests that they don’t.

At Ketamine Clinics of Los Angeles, co-founder and anesthesiologist Dr. Steven Mandel said contact with a mental health provider “ranges from no contact to two or three times” a week. Sam Mandel, an entrepreneur who opened the clinic with his father, Steven, and now serves as chief operating officer, said the only reasons the clinic wouldn’t stay in contact with patients’ mental health provider is if they don’t make themselves available or if a patient doesn’t have one, in which case the staff works with the primary care provider.

Many clinics don’t require patients to continue seeing a mental health provider, which means that ketamine becomes the sole source of mental health care for patients who can be among the most complicated to treat. “When there’s no sort of collaborative involvement, that’s worrisome,” Lieberman said.

Dr. Nora Janeway, a primary care doctor in New Hampshire, recently found out that a young patient had just received a series of infusions at a ketamine clinic run by two nurse practitioners.

Her heart sank: This was a particularly complex patient who first came to Janeway’s office a few months ago on a slew of psychiatric prescription drugs, including two benzodiazepines, an antipsychotic, a mood-stabilizing medication, and a stimulant. Janeway wanted the patient to connect to a psychiatrist to manage those medications, but that hadn’t happened yet when the patient started receiving ketamine. Janeway said she was never contacted for records or notified of her patient’s treatment.

“There’s no sense of obligation [in regards to] continuity or follow-up of the patient,” she said.

Basurto, the patient who has received nearly two dozen ketamine infusions since last October, hasn’t seen a mental health provider in six months, he said. Belnap, the anesthesiologist who oversees Basurto’s treatment, said he strongly encourages patients to see an outside mental health care provider, but he can’t force them to do so. He noted that many patients taking traditional SSRI antidepressants for long periods aren’t undergoing psychotherapy either.

In many cases, ketamine providers aren’t qualified to provide mental health care on their own. They’re often anesthesiologists or pain physicians, and in some cases, nurse practitioners. STAT’s review of staffing found that many clinics have no mental health providers on staff. Clifton and his three co-founders are each in the San Antonio office one day a week — and on Tuesdays, a physician assistant staffs the office. Two of Kalypso’s affiliated clinics are run by physician assistants, another is run by a primary care doctor, and the last by a pain physician. Clifton and his co-founders train those providers for a few days and then oversee the care at those clinics through a management service agreement, he said.

The APA says that whoever is providing ketamine treatment needs to be trained in how to address behavioral health problems, because ketamine can cause dissociative effects such as hallucinations. The organization also says it’s critical that clinics have caregivers qualified to make sure patients aren’t at risk for behavioral problems — including experiencing suicidal thoughts — before they’re sent home.

Anesthesiologists, in turn, argue that psychiatrists aren’t qualified to provide ketamine treatment on their own. They’re not prepared the same way anesthesiologists are to deal with problems that could crop up during an infusion, such as an irregular heart rhythm or more serious cardiac issues.

Belnap noted that the safety information included in every box of ketamine says that the physician administering ketamine should be trained in using anesthetics and managing problems with a patient’s airway.

“I’m not saying psychiatrists can’t [administer ketamine], but they need to have someone in the room or in the clinic who knows ketamine — because they don’t,” Belnap said.

One thing is clear: Collaboration is critical.

“You don’t treat an advanced disease with just an infusion and a ‘see you next time,’” Cusin said. “If [doctors] replace your knee but don’t do physical therapy, you don’t walk again.”

But in some clinics, that appears to be the case, experts said.

Even in her clinic at Mass. General, staffed with experts used to dealing with complicated mental health issues, Cusin won’t allow a patient to receive ketamine if that person doesn’t have a primary mental health provider. She and her colleagues can’t provide both ketamine treatment and comprehensive psychiatric care themselves.

“It’s hard. It’s unrelenting. There’s always someone relapsing,” she said.

Studies vary but have found response rates to ketamine as high as 70 percent among people with major depression who have failed a few other antidepressants, Cusin said. But the rate is lower for patients with extremely treatment-resistant depression, and how long any improvement lasts varies from one patient to the next. Cusin carefully explains what patients can expect during the informed consent process, and also talks with their therapist. Not all clinics lay such a thorough foundation.

The stakes couldn’t be higher for patients, Cusin said: “Imagine if you take out a loan for $5,000 or $6,000 for treatment, and it doesn’t work. That could be heartbreaking.”

‘They’re throwing bait in the water’

A number of clinics’ websites pump up the promise of ketamine with the same four-year-old quote from Dr. Thomas Insel, the former director of the National Institute of Mental Health: “Recent data suggest that ketamine, given intravenously, might be the most important breakthrough in antidepressant treatment in decades.”

They neglect to include another line that appears a few paragraphs down in Insel’s 2014 blog post about ketamine: “There are still a number of questions to resolve about the best dose, the mechanism, and the long-term efficacy and safety of ketamine.”

Asked recently by STAT whether he was concerned about the use of his truncated quote in the promotional material, Insel responded by noting many caveats when it comes to ketamine treatment for mental health conditions, but said he had “no regrets’’ about the post.

Insel, now president of Mindstrong Health, a medical technology company based in Palo Alto, Calif., said “optimal care for someone with a depressive disorder requires careful diagnosis and comprehensive treatment.”

“I suspect that does not happen in every ketamine clinic,” he added.

The use of Insel’s quote is a prime example of the way some clinics aggressively promote the potential of ketamine while underselling its risks and limitations. Victory Medical, a ketamine provider in Texas, for example, says on its site that “the path to happiness begins with the first session.” The website for Sierra Ketamine Clinics in Nevada proclaims that “patients who have lost hope and thought they would remain in the grips of chronic pain and mental illness for the rest of their lives have emerged across the country with renewed spirit and joy.”

Mental health specialists said they’re troubled by the way such glowing language might appeal to patients in need of help.

“They’re fishing. They’re throwing bait in the water and trying to lure people in,” Lieberman said.

Like Kalypso, some clinics offer special blends they say can curb side effects. But without published data, experts said there isn’t robust evidence to support those claims. Others make statements that similarly aren’t supported by strong, published evidence, including that their treatment plans work better than protocols published in scientific journals or that they can treat a slew of conditions with ketamine.

On its website, Kalypso says that it has a 91 percent success rate. Clifton told STAT the company offers ketamine for 32 conditions, including lupus and cancer-related pain. When asked whether there was evidence to support each of those uses, Clifton said “absolutely” and said the company is “compiling all of our data to be able to publish it all.”

At the top of its website, the company also prominently highlights its $199 genetic testing services to determine the “right formulation” of ketamine. But experts said genetic testing hasn’t been proven to offer any meaningful information about ketamine treatment at this point.

“We are currently still researching how to best use this test for patient therapy,” Clifton said.

Many clinics use social media to reach patients. To mark National Suicide Prevention Awareness Month, Rocky Mountain Mind & Body clinic in Colorado tweeted to its followers that it was offering a “special”: After patients finish an initial infusion series, they’ll get their first maintenance infusion free.

Some patients said they felt pressured to try ketamine, despite being unsure whether it was the right treatment for them. Alexia Taylor, a 41-year-old who has depression, called the New England Center for Healthy Minds in Acton, Mass., in February to ask about ketamine treatment.

She was floored to find out it would cost thousands and said she wasn’t interested.

“They didn’t want me to get off the phone,” she said. “They said, wouldn’t you like to feel better?”

The New England Center for Healthy Minds said that the screening and scheduling of patients is handled by an outside company called Neuragain, a network of ketamine providers. Julie Lassner, who works with patient and provider services at Neuragain, said the company’s receptionists only collect basic formation needed to secure an appointment, and then formal screening is conducted by the the Center for Health Minds.

All the providers STAT interviewed were quick to say they’re not prescribing ketamine to get rich. Clinics charge anywhere from $350 to upward of $1,000 for a single treatment — with a generic drug. Much of that money covers the significant overhead of running a clinic, providers said.

Most clinics offer a series of six infusions over two to three weeks, and many offer “boosters” as patients feel their symptoms creep back. It’s not clear whether all these infusions are necessary. According to the APA’s review of the research, the evidence is limited on the benefits and risks of longer-term treatment, such as monthly booster infusions.

Some patients scrimp and save for months to afford the treatments. Others ask friends and family to help them, put it on credit cards, or dip into their savings.

Insurers don’t yet cover ketamine treatment for major depressive disorder, because it hasn’t been approved by the FDA for a psychiatric indication. Levine, the Actify Neurotherapies CEO, said an estimated 40 percent of people who contact the company don’t end up scheduling an appointment due to cost. That, critics say, points to another possible issue: the high price will exacerbate health care disparities.

“The problem is, the patients who most need the treatment are the patients who can’t afford it,” Cusin said.

‘Whose job is it to rein this in?’

So what will it take to rein in rogue practices?

Mental health experts called for professional societies to follow in the APA’s footsteps and issue recommendations outlining training requirements and screening protocols for providers who treat mood disorders with ketamine.

The APA also strongly recommended that every clinic come up with standard operating procedures based on the best evidence available. That plan should outline clear steps for screening and obtaining informed consent; assessment of a patient’s physical and mental status before, during, and after infusions; and a plan for managing problems that crop up during or after treatment.

Another idea: create a registry to collect data on every patient who receives ketamine treatment for mood disorders. That will help provide more evidence on outcomes, both in the short-term and the long run.

Experts have pinned some hope — but not too much — on the FDA approving one of the new treatments in the works. A drug approval would mean clear information on dosing, treatment protocol, and indications for which a treatment is approved. And it could clear the path for insurance coverage; if insurers are involved, screening might be more stringent and more people would be able to afford treatments.

None of those are surefire fixes. Ketamine can still be offered off-label to patients with a range of conditions. As clinics continue to crop up, experts are skeptical that use of ketamine will become standardized any time soon.

“Whose job is it to rein this in?” Lieberman said. “Nobody’s gonna come down on them unless something happens.”

[Read the Original Post Here]