Ketamine is emerging as a potential new treatment for some types of depression.

A new review published in the Harvard Review of Psychiatry outlines the promise and limitations of existing ketamine research.



Some researchers have called the drug "the most important discovery in half a century."

It's been called "the most important discovery in half a century," and for some of the people who have tried ketamine, it may feel that way too.

The compound has a reputation as a party drug, but ketamine is increasingly being studied for its potential use as a rapid-fire treatment for depression. In people who live with the disease, thoughts of suicide can strike suddenly and without warning. Fast-acting, successful interventions are hard to come by.

But a spate of recent research suggests that ketamine could provide quick and powerful relief — even to people whose depression has repeatedly failed to respond to other medications and to those who are suicidal.

Experts say they're onto something promising. In a field that hasn't seen a new class of drugs in nearly four decades and in which patients are often desperate and suicidal, that kind of sentiment holds a lot of weight.

"Imagine arriving in the emergency room with severe pain from a kidney stone — pain so bad that you can't think. You'll do anything to make it go away. And the doctors say, 'here's a drug that we've been using for 30 years, it works 50-60% of the time, and it should start to work in 4-6 weeks'" Cristina Cusin, a psychiatrist at Massachusetts General Hospital and an assistant professor at Harvard University, told Business Insider. "That's currently the best we can do" for someone who is suicidal.

Cusin co-authored a large new review of the existing research on ketamine that was published this month in the Harvard Review of Psychiatry. Her findings shed light on the need for new treatments, but she also advises caution for patients.

"We are just scratching the surface of the mechanisms of action with ketamine," Cusin said.

Trying to tackle a uniquely troubling problem

For her review, Cusin looked at almost 40 ketamine studies that involved brain imaging.

Cusin faced challenges in assembling very different studies into one review, but she came up with some key takeaways. For one, she observed that people given ketamine experience measurable brain changes — many of them in areas that have been tied to our ability to process and regulate emotions.

Ketamine also appeared to increase activity in parts of the brain linked with reward processing, which would help to explain some of its antidepressant effects.

Nine out of 10 people who die by suicide have a mental illness at the time of their deaths, according to the American Foundation for Suicide Prevention (AFSP). But current interventions for those who find themselves contemplating suicide are limited to hotlines, sedative drugs, and talk therapy.

Rates of suicide in the US have risen steadily over the past few years, with roughly 123 people dying this way per day, according to the AFSP. Men die by suicide 3.5 times more often than women.

The reasons behind this rise are complex, but two of the biggest problems are a lack of access to mental health care and the stigma that continues to shroud mental illness.

"If you have asthma, it’s not considered your fault. But somehow if part of your brain isn’t functioning, it’s your fault," Cusin said. "It's a residual leftover from more ignorant times."

It's easy to see why the prospect of a new approach would inspire hope.

The promise of a new drug

Physicians and psychiatrists have been doling out the same drugs to people with depression for decades. But research suggests that while antidepressants can work wonders for some people, they don't help everyone. The medications also come with a range of unpleasant side effects that can include weight gain, less interest in sex, anxiety, and insomnia.

Like Cusin, most scientists who work in the space think it's time for a new tactic.

Some of them have found hope in recent months in psychedelic drugs like ayahuasca and magic mushrooms — which appear to reduce depressive symptoms by increasing the connectivity among previously segregated parts of the brain. But those drugs are widely illegal, and many people aren't interested in having a full-blown psychedelic experience.

Several recent studies published over the past few months suggest that ketamine could be the alternative drug people are looking for, since it is legal and also appears to work quickly.

Last December, researchers at Columbia University Medical Center who were working with depressed and suicidal patients found that ketamine worked significantly better at curbing their suicidal thoughts than a commonly used sedative. Most participants in the study saw their moods began to lift within 24 hours. In some people, those effects lasted more than a month.

The authors of a 2012 review of four preliminary studies on ketamine in patients with severe depression expressed surprise at how rapidly the drug appeared to produce positive, precise results.

"The findings were unanticipated, especially the robustness and rapidity of benefit," the authors wrote in their paper. "Ketamine appeared to directly target core depressive symptoms such as sad mood, suicidality, helplessness and worthlessness, rather than inducing a nonspecific mood-elevating effect."

The researchers behind another 2012 study on the drug went called ketamine "the most important discovery in half a century."

Ketamine's promise has not gone unnoticed among pharmaceutical companies. Johnson and Johnson is developing a form of ketamine that could be better tolerated and would be marketed as an antidepressant. And Allergan is in the last phase of clinical trials with a drug that acts on the same receptor as ketamine.

However, Cusin believes we need more research.

The biggest unanswered question: long-term effects

Some people with depression are opting to pay for pricey treatments at a range of clinics currently offering the drug — if they can afford it. Treatments can cost between $400 and $1,000 per infusion, and most clinics recommend that patients receive more than one ketamine infusion to get the maximum benefit.

However, the Food and Drug Administration has not approved the existing drug or any new formulation of it to treat depression. Using ketamine as an antidepressant is therefore considered "off-label," which means it is up to health insurance providers to decide whether to offer patients any reimbursement.

This is a vial of the animal tranquilizing drug ketamine hydrochloride, better known in the drug culture as "Special K." Authorities say that the drug "Special K," which is legal in most states with no penalties for possession, is showing up at teen-age parties all over the country. Several Massachusetts veterinary clinics have been burglarized according to police by thieves searching for the drug. AP Photo/Victoria Arocho

Plus, like any drug, ketamine has risks and side effects; some studies suggest that could include blood pressure complications. Most importantly, we don't have many studies that tell us what happens in the long term after a ketamine infusion. Most existing ketamine and depression studies have been limited to several weeks, so it remains unclear how long the benefits last and what the long-term effects may be.

Because of these complications and unanswered questions, many people wanting to try ketamine for depression are left in a sort of limbo.

But Cusin believes the drug "absolutely has potential."

"In the next few years I'm really hopeful that we’re going to see new drugs that are completely different than what we have now," she said.

