6 Things to Know About Antidepressant Ketamine

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 antidepressant.

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, Chicago and Los Angeles to Jackson, Wyoming, and Montpelier, Vermont.

The clinics all offer a controversial medical treatment using ketamine infusions for depression. Ketamine is approved by the Food and Drug Administration (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 if it works, 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 uncertainties.

Here are six things you should know about ketamine as a treatment for depression:

1. Antidepressant Ketamine is reserved for the worst cases

Depression is very common in the U.S. A 2019 CDC (Centers for Disease Control and Prevention) survey found that 18.5% of American adults aged 18 and up suffered from depression in the two week period prior to the survey — 21.8% of women and 15% of men. And the COVID-19 pandemic made it worse. Research in 2020 found that the prevalence of depression during the pandemic was more than three times higher than it was from 2017 to 2018, based on CDC data, with severe depression increasing more than five-fold.

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 Cristina Cusin, MD, associate professor of psychiatry and director of the ketamine clinic 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. Research suggests that ketamine infusions may also help improve symptoms of posttraumatic stress disorder (PTSD), a chronic and sometimes disabling syndrome resulting from exposure to a traumatic event. In a 2021 study published in The American Journal of Psychiatry, researchers administered either six ketamine infusions or six infusions of a psychoactive placebo to 30 people with chronic PTSD over a two-week period. Those given ketamine showed significantly greater improvement in PTSD symptoms than the placebo group, with improvements lasting 28 days after the treatment ended. 

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 a clinic or hospital and undergo intravenous  infusion treatments that require time and monitoring.  In March 2019 a nasal spray form of ketamine known as esketamine (Spravato)  was approved by the FDA as a fast-acting treatment for people at risk of suicide due to depression. In a phase III clinical trial sponsored by the drug’s manufacturer Janssen Research & Development, published in 2020, people who were moderately to extremely suicidal were given oral antidepressants and either eskatamine or a placebo nasal spray twice weekly for four weeks. People given esketamine showed greater improvements in depression scores at four hours, 24 hours and at various time points over the four-week study period. Similarly, a study in JAMA Psychiatry showed benefits over placebo in a 16-week study. Some experts have since questioned the efficacy and safety of the drug, in part because in clinical trials three study participants committed suicide after their last dose of esketamine. And some feel that the drug was pushed too quickly through the FDA approval process.

Intravenous (IV) ketamine treatments aren’t the same as the nasal spray or 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 Mark S. George, MD, professor of psychiatry and behavioral sciences at 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 to 30 minutes after a treatment, but patients aren’t allowed to drive home afterward, said Allison Wells, MD, an anesthesiologist at Superior Pain Relief, a pain clinic in The Woodlands, Texas. 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 may not be expensive, but the equipment and monitoring needed to provide infusions are. Patient costs can add up quickly. Intravenous ketamine treatments can cost from $400 to $800 each, and patients often start with six infusions over two weeks.

According to Dr. Wells, the Texas anesthesiologist, “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 2020 report in the journal BMJ General Psychiatry notes that  “the studies that were made for testing ketamine are relatively small and some of the studies made showed considerable risks for abuse and addiction.” 

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.

6. Antidepressant Ketamine comes with a risk of dependence and abuse

The 2020 report in the journal BMJ General Psychiatry also noted that ketamine can be abused in any administered form, intravenously or nasally, and ketamine has a potential risk of abuse by patients self-medicating for depression. According to the U.S. Drug Enforcement Administration ketamine has the potential for abuse and its use may lead to physical or psychological dependence.

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.”

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Tim T

I currently am undergoing regular Ketamine Treatments (I have done dozens) and this article is very misleading, and straight up WRONG in some places:

In point 2 he said “For one thing, ketamine isn’t available as a pill.” YES, it is. The tiniest amount of research would have revealed this. It can be prescribed it in the form of a Troche (a gelatin pill you dissolve in your mouth). I know, because I have a prescription for it, and it costs around $10/treatment without insurance. The author is correct about the prohibitive costs of the intravenous treatments (~$500), but there are also Intramuscular (~$200), and Nasal Spray (Spravato) which is FDA approved and covered by insurance, and has been for 2+ years.

For point 3, the author is mostly correct except that those “better options” have a HUGE list of serious side effects, especially electroconvulsive therapy, which can permanently alter your personality and memory. Ketamine will give you a psychedelic experience (during treatment) and might make you nauseous and dizzy for a few hours, that’s about it.

For point 4. Spravato is FDA approved and covered by most insurance, it seems like the author did little to no research on the topic. They are correct that there are a lot of less reputable clinics pushing the intravenous treatments, which should be avoided, but the costs can be mitigated. I didn’t have insurance and it cost me around $1,500 for my initial treatments, and now have a prescription that is around $40/month. Though at home self-treatment may not be available if you are high risk of abuse or your provider doesn’t feel comfortable with it.

Point 5. “The consequences of long-term use are not known,”… yes they are. The most common being incontinence, but these only become an issue with abuse. Low dose, once a week has almost no long-term side effects. The official studies are still being conducted but if you include the research on Drug abusers and chronic users you can paint a clear picture. It’s extremely safe if taken as directed.

Point 6. Yes, there is a risk of abuse and dependance, but it’s just that a “risk”, not a guarantee. Tylenol comes with a risk of Liver damage, and is one of the safest drugs. If you are responsible and looking for a solution and are willing to be 100% adamant with dosages and following directions, there is little to no risk.

There are 2 big problems with Ketamine, One: The stigma of it being a “Drug” and not a medicine. It’s obvious to me that the author feels this way about it as well. Yes it is a psychedelic, yes it is used as a party drug. Imodium A-D is also used as a party drug, and that’s over-the-counter. Doctors have know that Ketamine helped with PTSD since the Vietnam war, but Nixon’s “War on Drugs” made any research into it illegal because of these biases and stigmas.
The second problem is that it only lasts a week to a month, so it isn’t a long term solution. Psilocybin can last 6 month to years, but the research is still ongoing (I expect it will be approved by the FDA within the next 5 years).

This article is misleading and filled with false information that cursory google searches could debunk. I will repeat, I have and am still undergoing the therapies and they have been life altering. The day after my first treatment I felt positive emotions for the first time in 10+ years, my life wasn’t a miserable hellscape of self-loathing and dread, but a normal life where I could feel happy for once. This article is half-assed, go find better researched ones.

Sherri Carver

Not sure how this statement could be accurate: “ketamine has a potential risk of abuse by patients self-medicating for depression.” Perhaps the author doesn’t understand that ketamine, even the nasal spray version (Spravato), is administered in the doctor’s office, under medical supervision. The patient is not given access to the ketamine to self-administer the medication. Treatments are also expensive. Patients interested in “self-medicating” can surely find cheaper, easier alternatives (alcohol, medical marijuana in some states) that they can use in their own home.

Liz Smith

I have to question the obvious bias the writer has about this treatment. I have worked as a journalist, and as a communications & PR rep. for a Fortune 100 corporation. This article is extremely one-sided. It is truly shameful because so many people suffer debilitating depression and anxiety; those of us who do have been through hell trying different medications, doctors, & therapy. We have high hopes, digest potentially dangerous and expensive prescriptions for at least eight weeks again, and again, and again… to no avail. There are many more positive aspects to ketamine than this article presents. Don’t rely on this as the truth about ketamine.

P. David

The author needs to become better educated on the use of ketamine for sufferers of treatment resistant depression and PTSD. My considerable experience with it via IV, IM, and sublingual troches has been extremely beneficial in dealing with the recent trauma of losing my husband of 30 years to suicide. Antidepressants failed me; intense psychotherapy, while beneficial, was insufficient. I took a leap of faith in trying ketamine and it has likely saved my life.

Ellie Davis

It’s interesting to know that ketamine can help you to deal the worst cases of depressions. My husband and I are thinking about how to deal with his depression problems, and we are looking for advice. I will let him know about your recommendations to choose the right treatment for his depression. https://advancedketamineassociates.com/la-quinta

Anne Malone

I appreciated the small bit on post ketamine & potential booster doses. It would be great to see an expanded article on same , with much attention paid to time frames for boosters.
Even tho its quite individual, any info would be helpful. Most especially, individual experience with booster timelines & recognition of needing a booster. Thank you in advance.
Anne Malone .☮

shahriar khezri

As an anesthesiologist of 20 some years I am so sorry to see all these misinformation about Ketamine by this website!

shahriar khezri

and apparently my comment wont be approved, this website is using censorship which can potentially have legal consequences to the owner/ moderator of the page!

Kim Komar

This article is complete incorrect. Please do not take this at face value. Do your research! I’m so sad that this author is so mis-informed.

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