The anesthetic ketamine is increasingly being used off-label for depression. The drug seems to work rapidly, but its long-term side effects are unknown.
Two decades ago, ketamine was known as two things: an anesthetic used in pet surgery and a party drug nicknamed “special K” that was popular at raves. Now, it’s the hottest new treatment for depression that hasn’t responded despite psychotherapy or antidepressants.
How hot? Very. Dozens of ketamine “clinics” have popped up across the United States over the past few years, offering hope to people whose depression doesn’t respond to treatment. You’ll find them offering infusions everywhere from big cities like New York, Houston and Los Angeles to Boise, Idaho, and Charleston, S.C.
The clinics all offer a controversial medical treatment that’s approved by the FDA only as an anesthetic, not for depression. Ketamine is primarily used for starting and maintaining anesthesia. Your insurance company is unlikely to pay for ketamine infusions, the treatment’s long-term effects are unknown, and it may stop working over time.
So why is it so popular? There are claims that it alleviates depression rapidly – frequently in a matter of hours – though the effect can be temporary. And because those seeking care are often so desperate for relief, they’re willing to accept the risks, cost – a single infusion can cost hundreds of dollars – and the uncertainties.
Here are five things you should know about ketamine as a treatment for depression:
1. Ketamine is reserved for the worst cases
Depression is very common in the U.S. The CDC (Centers for Disease Control and Prevention) estimates that 8% of American adults aged 20 and up suffered from depression at any one time from 2013-2016 – 10% of women and 6% of men.
Ketamine isn’t a first-line treatment for depression. Instead, ketamine clinics focus on a smaller group: patients with so-called “refractory” or “treatment-resistant” depression that doesn’t respond to common treatments like talk therapy and antidepressants.
An estimated one-third of people with depression fall into this category, and their lives can be full of misery and suicidal thoughts. “Most of our patients have been severely disabled and impaired for many years,” said Dr. Cristina Cusin, a psychiatrist who studies ketamine at Massachusetts General Hospital. “A patient can get pretty desperate.”
2. Ketamine isn’t an easy or simple fix
At first glance, the news about the effects of ketamine sounds incredibly promising. Studies suggest treatment with ketamine can relieve depression symptoms in many patients in as few as two hours. It may go on to provide relief for as long as two weeks.
One patient with depression described the effects of ketamine this way in a 2015 National Public Radio report: “I remember I was in my bathroom, and I literally fell to my knees crying because I had no anxiety, I had no depression.”
As Dr. Cusin puts it: “There’s a lot of hope that this is a magic fix.” But ketamine isn’t easy to take, and it isn’t a simple solution even when patients respond.
For one thing, ketamine isn’t available as a pill. Patients must go to clinics and undergo intravenous — injected — treatments that require time and monitoring. A nasal spray form of ketamine known as esketamine is being studied as a fast-acting treatment for people at risk of suicide due to depression. Results from a small Phase 2 trial of the drug sponsored by Janssen, part of Johnson & Johnson, published in April 2018, showed those on esketamine demonstrated a significant reduction in depressive symptoms at four hours and 24 hours after administration, but not after that.
Intravenous ketamine treatments aren’t the same as a normal injection like a flu shot. Patients are hooked up to an IV for perhaps 40 minutes. The immediate effect is “like a light anesthetic,” said psychiatrist Mark S. George, MD, of the Medical University of South Carolina. “It makes you spacey and a little bit dreamy, but most people tolerate it.”
Most of the disorientation tends to lift within 15-30 minutes after a treatment, but patients aren’t allowed to drive home afterward, said Dr. Allison Wells, an anesthesiologist who runs a ketamine clinic in Houston. You may need to get someone to pick you up, although some clinics allow patients to ride home via Uber, she said.
There’s another complication: Ketamine isn’t a solo treatment. It must be used with complex regimens of other psychiatric medications that treat depression and anxiety, Dr. Cusin said. “If the expectation is to stop everything else and take ketamine,” she said, “it does not work this way.”
3. Other treatments may be better options
Ketamine is a good option for some patients, Dr. Cusin said, “but we consider many patients to not be appropriate because they haven’t failed other treatments that would be a good option.”
Alternative treatments include electroconvulsive therapy (formerly known as electroshock therapy), transcranial magnetic stimulation and older types of antidepressants. These are typically used before ketamine since there is more clinical evidence supporting their effectiveness.
Not all ketamine clinics have a psychiatrist or psychologist on staff to ask questions about the treatments you’ve tried. Many clinics are run by anesthesiologists who’ve pioneered the fledgling field of ketamine care, and some don’t have any mental health professionals on their staff. You may want to be wary of these clinics.
Critics don’t think this is a good idea. “It’s malpractice to not have a mental health professional involved if the disease being treated is depression,” Dr. George said.
4. Ketamine costs a lot, and your insurer probably won’t pay a dime
Insurers typically won’t pay for ketamine treatments. That’s because ketamine for depression is considered experimental since it hasn’t been approved for this purpose by the FDA. It’s legal for healthcare professionals to offer ketamine as an “off-label” treatment for depression. It’s not unusual for a doctor to prescribe drugs for a condition for which the FDA has not approved the drug.
Ketamine itself is cheap, but the equipment and monitoring needed to provide infusions are expensive. Patient costs can add up quickly. Intravenous ketamine treatments, which are known as infusions, can cost from $300-$800 each, and patients often start with six infusions over two weeks.
According to Dr. Wells, the Houston psychiatrist, “usually by four to six treatments, a patient can go four to six weeks between infusions.”
5. You might take ketamine forever…or not
How much ketamine should patients take and for how long? Research doesn’t provide much in the way of answers.
A 2017 report in the Journal of the American Medical Association noted that “most published data supporting the use of ketamine as a treatment for mood disorders are based on trials that have followed up patients for just 1 week after a single administration of the drug.”
Some patients have undergone ketamine infusions for years, while others have seen its effects fade over time. “The consequences of long-term use are not known,” Dr. Cusin said.
It’s also not clear if there’s a significant risk of addiction.
Dr. George, the Medical University of South Carolina physician, is so concerned about the various risks of ketamine that he only recommends its use in psychiatric emergencies, such as when a patient is suicidal and needs relief in order to make it to the next day.
Many physicians disagree with Dr. George about the appropriate use of ketamine. But one thing is clear: Even when ketamine works, patients aren’t instantly cured.
The psychological damage of depression — isolation, ruined relationships, loss of jobs — won’t get better on its own, with or without ketamine. “You need a good psychotherapist to work through the grief of everything you’ve lost,” Dr. Cusin said. “The medication isn’t going to fix that.”