New Jersey psychiatrist Steven Levine first thought of using ketamine in his practice when a patient came in whose depression could not be lifted by any commercially available antidepressants. After talking to Levine for a while, the patient confessed she felt better when she self medicated with cough syrup. When Levine looked up the active ingredient in the cough syrups the patient used, it was dextromethorphan, which, like ketamine, can induce a dissociative state or a detachment from reality.
You have to be looking in order to find something, says Levine, who is now one of a few practitioners who administer ketamine for depression, along with a few research centers. When he started out, dosing his first patient in 2011, he was as far as he knows the first to offer it outside a research setting. Levine was tired of the available drugs for depression, which have a high side effect profile and are ineffective for some patients.
Only around 45% of patients respond to traditional antidepressants, leaving a huge population that continues to suffer.
Levine was seeing patients who had failed on every class of antidepressants, who had submitted to dramatic last line treatments, like electroconvulsive therapy and transcranial stimulation, and were still depressed.
Unlike with traditional antidepressants, which can take weeks to show any impact, within a few hours, when Levine administered ketamine, it was obvious if it had worked or not. Patients “don’t wake up with a blue bird on their finger”, says Levine, but they do get better.
Since 2011, he has given ketamine to 600 patients. When he administered it only to patients for whom no other treatment had worked, Levine found that 70% got better using ketamine. For the past year he has also been treating patients who have not had any success on two types of antidepressants, and with the addition of that patient population, his success rate is now closer to 80-85%.
While ketamine is not indicated for depression, doctors can prescribe medications off-label at their discretion. Unlike other psychedelic drugs that have also been investigated for their ability to help treat mental illness, like MDMA, ketamine is a legal, widely available and easy to procure medication, says Levine.
Ketamine’s ability to lift people out of severe depression, replicated over and over in research studies, has not gone unnoticed. Unlike in 2011, when Levine first started using it, there are now hundreds of medical studies on ketamine. The American Psychiatric Association (APA) is working on creating official guidelines for administering the drug, which are expected out this year.
Ketamine is administered intravenously to patients. If a patient responds positively to ketamine, they are given a series of doses close together over a couple weeks, followed by spread out maintenance doses. Therapy is recommended in conjunction, to help patients rebuild their lives after depression and maintain their improved state.
Levine is hopeful that after the APA issues its guidelines, insurance coverage will soon follow. He has been speaking with insurance companies, and they have said they would be open to covering the drug when there is an official protocol from the APA.
Ketamine, which has been on the market as an anesthetic for many years, is a generic, inexpensive medication, though its intravenous administration, done at the doctor’s office, does add treatment costs.
Pharmaceutical companies, never one to let a lucrative opportunity pass them by, are attempting to develop easier to administer version of ketamine that have fewer psychedelic effects, as well as exploring other drugs that target the same neurotransmitters and receptors. Johnson & Johnson, which is developing an inhaled version of ketamine, may be the first to reach the market, says Levine.
Ketamine has several mechanisms of action. It promotes neuroplasticity, new learning and has anti-inflammatory properties, explains Levine. But interestingly, the psychedelic impact of the drug may also be part of the reason it works. Attempting to remove it to make a more traditional depression drug may create a diluted, less effective version, he cautions.
Liz Lehmann, one of Levine’s patients, is quick to admit that the dissociative effect of the drug is wonderful. She describes it like being a lava lamp: flowing, warm, tingly, relaxed but energized at the same time. When she is getting a dose she feels like she can breathe easily, she tells me.
Before starting treatment with ketamine, Lehmann says she had trouble getting out of bed and wanted to hide all the time. She was textbook depressed, barely functioning, she explains. She had been in countless hours of therapy and tried a laundry list of medications to treat her depression.
When nothing helped, her psychiatrist at the time recommended she see Levine. Levine tried a few more conventional depression drugs but nothing really made a huge impact in treating Lehmann’s depression. That was when he suggested she try ketamine.
She was taken aback at first. She knew the drug primarily from its reputation as a common animal tranquilizer and a party drug. But after doing some research on it, she decided to give it a try.
The difference in her life before and after the ketamine treatments is striking, she says. Where she stayed in bed and “did the bare minimum” before, she is now learning the guitar and spending time with friends. She recently took the polar bear plunge with her son. She says ketamine gave her back “an interest in life”. When she talks about the difference the treatments made in her life, her voice – already cheerful – becomes boisterous. She jokingly says her family describes her visits to get maintenance doses as “Liz going into the K-hole”, a slang drug term for the dissociative state brought on by ketamine.
Like Levine, Mason Turner, chief of psychiatry at Kaiser Permanente San Francisco Medical Center and assistant regional director of mental health for Kaiser Permanente in Northern California, also sees the dissociative effects of ketamine as integral to its ability to treat depression. The dissociation experienced by the patients on ketamine has something to do with activating the neurotransmitter system and is part of the action of the drug, says Turner. Ketamine clears away the negative thinking of patients with depression and allows them to see life in a more positive way, promoting new learning. “We can reverse years of negative thinking about oneself after one treatment,” he tells me.
He cautions, however, that the medication does not work for everyone. Kaiser has been offering the treatment for a little over a year and has found that about 75% of patients with treatment-resistant depression respond to ketamine, results similar to Levine’s patients.
Ketamine is not the only psychedelic treatment that has a positive impact on depression. There are also studies looking at using psilocybin, the active ingredient in hallucinogenic mushrooms, as a treatment for anxiety and depression. With psilocybin, which is in earlier stages of research than ketamine, the psychedelic experience also seems to have an impact in alleviating depression.
“In general, there is a correlation with patients having a subjective peak experience and reduction in symptoms,” says George Greer, co-founder and medical director of the Heffter Research Institute, who has researched the use of psilocybin in alleviating anxiety in advanced cancer patients. The Heffter Research Institute funds scientific studies using hallucinogens and psychedelics. “Probably both neurobiological effects and subjective experiences are involved in the reduction of depressive symptoms,” says Greer.
It may take some time to get the general public used to the idea of treating mental illness with drugs many associate with destructive behavior and hard partying. The main roadblocks to wider adoption are the necessity of having office-based administration of the drug, says Levine, instead of the convenience of taking a pill at home.
There are also misconceptions around its abuse potential, says Levine. Ketamine is a schedule III drug, along with other drugs like Tylenol with codeine and anabolic steroids. While ketamine is abused as a recreational drug, the doses given to patients for depression are low and in a controlled environment. The intention of a ketamine dose matters, says Levine, adding that he sees no abuse potential when it is administered in a medical setting with no easy access to the drug.
With all the renewed interest in psychedelics, widespread acceptance may not be too far behind. The Heffter Research Institute is planning to support a phase III study needed to get FDA approval for using psilocybin to treat depression and anxiety in cancer patients, says Greer. It is his hope that 20 years from now psilocybin will be commonly used in psychiatric practice. Levine estimates that the first branded version of ketamine for treating depression could be available as soon as 2019.
Turner says it has been gratifying as a psychiatrist to be able to offer a medication that works so well. “We feel like we have saved some people’s lives with this treatment,” he says, referring to ketamine.
Now researchers and doctors have to figure out when to give patients the drug. Is it after they have failed other antidepressant medications and treatments? After patients failed to improve after trying five or 10 or 15 treatments? Or should something this powerful be offered as a first line treatment?
The answer is one that that many sufferers of depression and their families will be anxiously awaiting in the years to come.
guardian.co.uk &169; Guardian News & Media Limited 2010