Let's Talk Therapy

The Complete Guide to Ketamine Therapy for Depression, From Someone Who’s Tried It

Ketamine is an anesthetic that's used off-label for depression, but does it work?
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This piece is part of Allure's Let's Talk Therapy series. Read the rest of the series here.

When I entered the ketamine clinic for the first time, I started crying almost immediately. This was for two reasons: First and foremost, I was scared. After watching a documentary that introduced me to the subject and reading several accounts of ketamine infusion therapy, I knew a fair amount about the process. But the experience sounded strange, disorienting, and mysterious. Despite having done my research, I still didn’t feel like I had a good idea of exactly what it would feel like.

I was also crying simply from sadness. I’d been trying for almost 10 years to manage my depression with medications and therapy but felt worse than ever. The many medications I’d been prescribed over the years would work for a little while, then inevitably stop being effective, sending me into a progressive spiral that would worsen every time. I felt like I'd tried everything, but that wasn’t quite true. I hadn’t tried ketamine.

Ketamine has been used as an anesthetic since the1960s. In the 1990s and 2000s, researchers began looking into trying it off-label as an antidepressant. Fairly recently, it has come into use for people with treatment-resistant depression, as well as people with other diagnoses, like bipolar disorder and post-traumatic stress disorder (PTSD). (It’s also used for treating pain.) Ketamine clinics have opened in select states throughout the U.S., including California, where I live.

Ketamine is available in a couple of different forms: It can be administered through an IV or ingested via a nasal spray called esketamine. Esketamine is approved by the FDA for the treatment of treatment-resistant depression. IV ketamine is not, and thus treating depression with ketamine is an off-label use. Ketamine lozenges are also available to some patients.

I was about to give IV ketamine a try, and although I was terrified, the unknown was preferential to continuing on the same path I was used to because it came with a massive potential benefit: finally finding relief from my depression.

What Ketamine Can Do for Depression

Ketamine has been shown to be effective in treating symptoms of depression and can be especially helpful for treatment-resistant depression (TRD), which is generally defined as “inadequate response to at least one antidepressant trial of adequate doses and duration,” according to a study published by Harvard Medical School. If you’ve tried multiple antidepressant medications (possibly in combination with other treatments) without success, you might have treatment-resistant depression.

In several studies at Yale, more than half of the participants who were given ketamine infusions showed a significant decrease in symptoms associated with depression after only 24 hours. These results are significant for two primary reasons: One, these participants were people who had experienced no “meaningful improvement” on other antidepressants. Two, the alleviation of depression symptoms after just 24 hours is extremely fast compared to other antidepressants, which can take weeks to kick in. To a severely depressed person who might be experiencing suicidal ideation, a fast-acting treatment could make all the difference in the world.

John Krystal, the Robert L. McNeil Professor of Translational Research and chair of the Yale department of psychiatry, believes that ketamine is a promising treatment for depression for several reasons. First, it can be effective for people whose depression symptoms have not responded to other treatments. Second, as noted above, the effects are rapid. “People who are severely depressed, suicidal, and might otherwise need hospitalization may get better as quickly as 24 hours after their first dose,” says Krystal.

A third reason is that ongoing ketamine therapy can protect a patient against a return of depression symptoms. “The reason that this is so important is that even after trying many different treatments, as many as 30 percent of patients will remain significantly depressed,” Krystal tells me.

How It Works

Robert C. Meisner is the medical director of the McLean Ketamine Service in the psychiatric neurotherapeutics program at McLean Hospital, the major psychiatric hospital for Harvard Medical School. In an article for Harvard, he writes that experts aren’t exactly sure how ketamine works to combat depression, but that one likely target is N-methyl-D-aspartate (NMDA) receptors in the brain. “By binding to these receptors, ketamine appears to increase the amount of a neurotransmitter called glutamate in the spaces between neurons,” Meisner writes. Then it activates connections in another receptor, called the AMPA receptor.

“Together, the initial blockade of NMDA receptors and activation of AMPA receptors lead to the release of other molecules that help neurons communicate with each other along new pathways,” writes Meisner. This process likely affects mood, thought patterns, and cognition.

Ketamine may also reduce symptoms of depression in other ways, such as reducing signals involved in inflammation. Meisner and other experts theorize that ketamine likely works in several different ways at the same time.

Potential Risks of Ketamine Therapy

I asked Meisner about the risks of ketamine therapy, including whether ketamine can be addictive. “All of us who specialize in this area remain concerned about the potential for physiologic and psychological dependence,” he tells me. At his clinic, for example, a previous history of substance use usually means a patient will not be treated with ketamine (though there are some rare exceptions).

“It’s important to understand that even though you may suffer from treatment-resistant depression, ketamine may not be the wisest choice,” he says.

That said, Meisner and his colleagues have not seen a high volume of patients who show signs of ketamine addiction. “To the best of my knowledge, we have received only one consultation request over the phone in which the caller was seeking treatment with ketamine for reasons consistent with addiction,” he tells Allure. “Moreover, to the best of my knowledge, not a single one of our patients has gone on to develop physiologic or psychologic dependence to ketamine after completing our protocol.”

However, experts remain alert about any potential for abuse. Currently, there is an epidemic of oral ketamine abuse in parts of Asia. Ketamine as a street drug is quite a different experience from ketamine as a treatment for depression (and street drugs carry the risk of being cut with other substances), but epidemics like this are always cause for concern.

In addition, there are some basic physiological changes that happen when ketamine is administered, such as a rise in blood pressure. For many patients, this isn’t a problem, but if you have some preexisting conditions, it may pose a health risk. That’s why it’s so important to find a ketamine clinic that prioritizes safety.

The Financial Cost

Ketamine therapy isn’t cheap. When I was determining where to go for my ketamine infusions, I asked about pricing at several clinics. The range I found in the Los Angeles area was $450 per infusion (the lowest price I could find) to $750 per infusion. Anecdotally, the highest price I’ve heard of is $1,000 per infusion. The clinic I ultimately went with charged $750 for the first two infusions and $600 for all subsequent infusions.

In other U.S. states, the price varies, but it’s never exactly an inexpensive option. (A map of “active clinics in good standing” from the website Ketamine Clinics Directory lists the price of ketamine infusions at clinics across the U.S. The lowest price listed is $250 per infusion, at a clinic in New Jersey.) Many clinics recommend six initial infusions, though of course, they can’t make you do any more than you want to.

The other big question associated with cost is whether health insurance will cover it. All of the clinics I spoke to in Los Angeles billed out of network, meaning that my insurance company might end up covering some of it, but either way, I would have to front the cost. (After many months, I am still waiting to hear back from my insurance company about whether I will be reimbursed for any of my treatments.)

If you have health insurance, you’re at the mercy of your insurance company to determine whether they’ll cover any of your ketamine therapy. To be fair, this is true of most medical procedures that are still considered experimental. I haven’t found a clinic that is an in-network provider for any health insurance plans, although that doesn’t mean they don’t exist. If you don’t have health insurance, of course, you’ll be paying the cost yourself. This can add up to many thousands of dollars, depending on the number of infusions you receive. On the bright side, some ketamine clinics offer payment plans.

If you are able to find an academic center in your area, the pricing may be different. At this time, it’s difficult to find any comprehensive list of prices throughout the U.S., so it’s important to call around and ask for pricing information when you’re doing your research.

What It Feels Like

This remains the most difficult part of the ketamine process to describe. Even after seven sessions, I never got very good at describing what it feels like to undergo a ketamine infusion.

I spoke to a writer, who I’ll call Rebecca for the purposes of anonymity, who was prescribed esketamine after suffering from treatment-resistant depression for many years. She described her first two experiences of esketamine (which were a higher dose than her subsequent doses) thusly: “There was a physical sensation of heaviness but at the same time I felt separated from my body. Or it might be more accurate to say, separated from my consciousness. I was able to view certain things more objectively. Things that were upsetting suddenly seemed less important.”

This description rang true for me. If you’ve ever done a hallucinogen, like LSD or mushrooms, this probably all sounds familiar to you. Ketamine felt similar to other hallucinogens but way more intense, and for me, it lacked any feeling of euphoria, though I did find myself laughing during several of the treatments.

Now, Let's Talk Results

Like almost anything, the effects of ketamine therapy vary greatly from person to person. Studies show that ketamine is associated with a rapid reduction in depression symptoms, including suicidal ideation. Overall, ketamine is promising in terms of its general effectiveness, as well as its fast-acting properties.

However, that doesn’t mean it will be effective for every individual. Like any treatment for depression, there is, unfortunately, no way to test whether it will be effective for a given person. When intravenous ketamine does work, patients usually respond to it within one to three treatments. If a patient doesn’t respond at all to those initial treatments, further infusions are not likely to be effective.

In addition, most experts agree that ketamine works best as part of a larger treatment plan, which usually involves talk therapy and sometimes ongoing use of antidepressant medication. Meisner says it’s important to remember that ketamine is not a magic bullet.

In my case, the first two treatments did not feel effective to me, although I experienced mild euphoria for short periods after each of them. After my third infusion, though, I began to feel significantly better. Many of my symptoms subsided, I felt “lighter,” and I laughed a lot more.

Between my third and sixth infusions, and for about a week afterward, I continued to feel relief from my previous symptoms. Unfortunately, that relief faded quickly. My symptoms returned about a week after I finished my sixth infusion. Ketamine’s effects are known to be relatively short-term; the staff at my ketamine clinic told me that most of their patients feel relief for about three months after completing six infusions. I was one of the people who experienced its effectiveness for a very short time. After trying a seventh infusion, I was prescribed ketamine lozenges, which are supposed to prolong the effects of the ketamine infusions. I do find the lozenges effective, though for very short periods. For me, their effects last about a day.

However, I spoke to other people who reported success with ketamine therapy. Rebecca, who takes esketamine for depression, has experienced a significant reduction in her symptoms.

Her first two doses were eight sprays each, taken under the doctor’s supervision, followed by a “maintenance dose” of two sprays a week. Rebecca told me that she experienced immediate positive effects, that it boosted her energy levels and took the edge off her depressive symptoms. Before the ketamine treatment, her depression was causing her debilitating levels of “brain fog,” negatively affecting her memory and cognition. She feels that the esketamine is helping with that. She says that after about a month and a half of treatment, she’s cautiously optimistic.

How to Seek Out Ketamine Therapy

If you’ve been diagnosed with major depressive disorder (MDD), bipolar, or PTSD (or some other diagnoses, in some cases), and other treatments haven’t helped you, you might be a good candidate for ketamine therapy. However, it’s important to get an opinion from your psychiatrist first as to whether ketamine is a good option for you. “[They] may not be especially familiar with these emerging treatments, but they should understand your response to first-line antidepressants and be able to offer an opinion regarding the likelihood that further trials with more established medications will yield different results,” says Meisner.

Start by researching ketamine clinics in your area. Again, this map is a handy place to start, though it’s not comprehensive, and the quality of each clinic is not guaranteed. If you don’t feel up to doing this research, this is a great project to ask a non-depressed loved one to do for you. The person doing the research should determine a reasonable distance from where you live and call any ketamine clinics in that area. They should ask about price, insurance options, payment plans, and how many initial sessions the clinic recommends.

Many clinics recommend six infusions within a two- or three-week period, so if you do go ahead with treatment, be sure to schedule them when you can spare that time. My infusions lasted 55 minutes each, plus 15 to 20 minutes of recovery time afterward — you need some time before you are steady enough to walk again. You also can’t drive yourself home after an infusion, and you will feel fuzzy and possibly sleepy in the hours afterward, so schedule accordingly. Also worth noting: My clinic instructed me to fast for four hours before each infusion.

What to Look for in a Ketamine Clinic

Additionally, many ketamine clinics will ask to be put in contact with a therapist, psychiatrist, or general practitioner who can confirm your diagnosis, so have that information ready. Meisner also stresses the importance of finding a ketamine clinic that’s evidence-based and data-driven, and that puts safety first. He has a few key recommendations for anyone considering ketamine treatment:

  • Seek out a specialist who is “not only willing — but enthusiastically supports — close collaboration with your outpatient psychiatrist.” Collaboration of this kind can be time-consuming and is often not reimbursed but is extremely important with “emerging treatments” like ketamine.
  • Find a specialist who is willing to be transparent about the uncertainties of ketamine treatment. “This is not a sub-field in which arrogance — of any kind — is a marker for competence,” says Meisner. “If you sense someone is overpromising, they probably are.”
  • Be relentless about ensuring that the clinic has appropriate safety measures in place. “Don't be afraid to ask what specialists are on sight, and why they are qualified for a psychiatric use of a medication typically categorized as an anesthetic,” says Meisner. For example: Are both a psychiatrist and an anesthesiologist present? What sort of training does staff have that qualifies them to administer ketamine? And crucially, what kind of monitoring is in place during treatment?

In all honesty, I wanted ketamine to cure my depression instantly and forever. Deep down, though, I think I knew it couldn’t do that. Ketamine isn’t for everyone, and it isn’t a magic bullet. But it taught me that my brain, as hopelessly entrenched in sadness as it sometimes seems, has the potential to change, and that it’s possible for me to feel better. For those of us who have spent a long time suffering and who have been unable to find an effective treatment, ketamine therapy offers a ray of hope. For some of us, that hope can be life-saving.


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