Ketamine gives hope to patients with severe depression, reports a Stat News investigation. But usage in the US is booming, with clinics hyping its benefits and using marketing gimmicks such as 'proprietary blends'.
Walk into Kalypso Wellness Centres in San Antonio, Texas, and you might be treated with one of five “proprietary blends” of ketamine. According to a Stat News report, they’re not cheap and not covered by insurance, but the company offers a “monthly” membership programme to cut costs and advertises discounts for members of the military and first responders.
The report says Kalypso promotes ketamine, long used as an anaesthetic 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 anaesthesiologist Dr Bryan Clifton.
The report says that Kalypso’s sweeping claims are hardly uncommon in the booming ketamine treatment business. Dozens of free-standing clinics have opened across the US 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.
The report says it 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; and clinics sometimes over-hype 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,” Dr Jeffrey Lieberman, psychiatrist-in-chief of Columbia University Medical Centre is quoted in the report as saying. 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 said in the report that they try to work with a patient’s mental health provider or another physician.
The report says 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.
The report says 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 fuelled 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 US Food and Drug Administration. But they say in the report that 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.”
The report says 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 behavioural therapy. “The pace of ketamine treatment in real-world practices has outstripped what researchers are able to do and publish,” Calabrese said.
The report says 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 – the report says 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.
“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.
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 anaesthesiologist 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.
The report says in many cases, ketamine providers aren’t qualified to provide mental health care on their own. They’re often anaesthesiologists or pain physicians, and in some cases, nurse practitioners and a review of staffing found that many clinics have no mental health providers on staff.
The APA says that whoever is providing ketamine treatment needs to be trained in how to address behavioural health problems, because ketamine can cause dissociative effects such as hallucinations. The organisation also says it’s critical that clinics have caregivers qualified to make sure patients aren’t at risk for behavioural problems – including experiencing suicidal thoughts – before they’re sent home.
Anaesthesiologists, in turn, argue that psychiatrists aren’t qualified to provide ketamine treatment on their own. They’re not prepared the same way anaesthesiologists are to deal with problems that could crop up during an infusion, such as an irregular heart rhythm or more serious cardiac issues.
The report says 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 Massachusetts 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.
The report says studies vary but have found response rates to ketamine as high as 70% 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.
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 report says 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.
The report says 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 sure-fire fixes, the report says. Ketamine can still be offered off-label to patients with a range of conditions. And as clinics continue to crop up, experts are sceptical that use of ketamine will become standardised any time soon.
“Whose job is it to rein this in?” Lieberman said. “Nobody’s gonna come down on them unless something happens.”
[link url="https://www.statnews.com/2018/09/24/ketamine-clinics-severe-depression-treatment/"]Stat News report[/link]