Q. I received a ketamine infusion several months ago and it literally saved my life. My 30+ year depression was severe (unable to feel, no relationships, unable to work, extreme anxiety and fatigue, etc). I volunteered for a study at the National Institutes of Health for patients with extreme, treatment-resistant depression, where I was given ketamine.

The effect was instantaneous and miraculous. All symptoms were completely relieved within two hours. The relief lasted about two weeks. Most of my fellow patients at NIH experienced the same. There are many doctors now using ketamine in clinical practice for severe depression. I had no trouble finding one and have since been treated with ketamine for several months.

You cannot imagine the sensation of decades of suffering draining away rapidly. For the first time in my life (age 50) I am finally able to get out of bed in the morning, experience joy, socialize, work, date, etc. Ketamine doesn’t work for every patient, but the response rate is astonishingly high (65-80%). If you are reading this post while suffering long-term, extreme depression: please consider volunteering for a ketamine study or find yourself a doctor who employs it in their practice.

A. Your experience has just been confirmed by new research published in the Journal of Psychopharmacology (online, April 3, 2014). A small study from the UK demonstrated that infusions of ketamine produced dramatic responses in severely depressed patients. Like you, some of these individuals had been suffering for decades.

Unlilke traditional antidepressants, which can take weeks to kick in, ketamine sometimes produces noticeable results within a few hours. The lead investigator, Dr. Rupert McShane, reported to the BBC that “It really is dramatic for some people; it’s the sort of thing really that makes it worth doing psychiatry; it’s a really wonderful thing to
see.”

Although some of the patients had long-lasting benefit, others relapsed. But keep in mind that ketamine is not given daily like typical antidpressants. This study involved three to six infusions over a period of three weeks. One wonders what would happen if the drug were administered orally on a regular basis or over a longer period of time.

Ketamine was originally approved for human use as an injectable general anesthetic in 1970. It is especially helpful when severe pain is involved, such as in burn patients or during emergency surgery. That’s because it is both an anesthetic and an analgesic, meaning that it provides significant pain relief while helping the patient remain unconscious. Because it opens airways, it is especially helpful for asthmatics or patients with COPD (chronic obstructive airway disease). Ketamine is also used by verterinarians for a wide variety of animal surgeries.

Caution about ketamine results in part because of its negative reputation as a club drug. The street name for ketamine is Special K. When taken orally, the drug produces a “dissociative” effect that some describe as detached or distorted. It is a shame that ketamine has been abused, since its antidepressant potential is so exciting. This may have delayed research into this promising treatment.

To learn more about ketamine in the treatment of severe depression, here is a link to an earlier post, “Old Drug Has New Tricks Against Depression.”

Let us know your experience with depression. If you have participated in a ketamine trial, we would love to hear your story. You may also find our Guide to Dealing with Depression of value.

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  1. Ppbear1
    Lewisville, TX
    Reply

    I have had marked problems with bipolar disorder for over 50 years (71 yrs. now). For the past 25 years, I’ve had problems with Complex Regional Pain Syndrome. I have also been diagnosed with Fibromyalgia in the past year. I suffer also from what I can only refer to as Chronic Fatigue Syndrome. As a veteran, I am trying to get help from the VA with no success. Pain doctors here in Texas are ultra conservative. My life has become a nightmare. Your help would be much appreciated.

  2. Laura P.
    Reply

    What is the worst side affect of Ketamine? I hope to try it as I have terrible depression.

  3. jale
    Reply

    Could you please provide an explanation/details about what is meant by a dissociative effect? What does the patient experience and is it lasting or fleeting? Profound depression alienates one from life and family; a lifting of the depression usually (hopefully) allows relationships with spouse and family to be re-established – if a dissociative effect is present might it impact that?
    People’s Pharmacy response: It is hard to describe this effect. It is different for different people. For some it has been described as a separation of body and mind.
    Here are links to Wikipedia descriptions:
    http://en.wikipedia.org/wiki/Dissociative
    http://en.wikipedia.org/wiki/Ketamine

    • Anonymous
      MD
      Reply

      The ketamine dose given in the NIMH study is far less than the amount folks use on the streets, and less than the amount used by anesthesiologists. In the NIMH study, not a single subject (healthy volunteer or patient) has withdrawn from the study due to dissociative side effects, or any other “psychotomimetic” side effects. (Almost 200 have enrolled to date- 10/02/14. )

  4. Helen M
    Reply

    I have read about successful use of ketamine in treating the pain of fibro. However, it, and any drugs used for pain relief need to be monitored, by the DOCTOR, not the government, and we must be careful that we do not deny pain relief to people who need it to function. Like me.
    I started with pain relief meds about 20 years ago, then for the relief of diabetic neuropathy and arthritis. I remember the first time I took a vicodin, it was like my body became 20 years younger. As the years have progressed, four cancers leading to other problems, my pain has grown worse. I now also have fibro. I carefully monitor my use, wherein I have a ceiling, and do not go beyond it. Mostly, I take the same dose day in and day out.
    If I have occasions of great pain, for instance after knee surgery, I monitor my usage by writing it down. As it happens, using more than my everyday dose causes severe constipation.
    At 76 I am not even half the person I was before pain became a part of my everyday life; however, missing certain organs, the medications I take, also have robbed me of ability and stamina.
    Far from the subject of ketamine. Reading your article has piqued my interest and I plan to do further research into this substance. Anything that will curb my appetite and help my pain migth be a good addition to the pharmacy of drugs I take. Now, if there was a way to increase my energy, I would definitely choose that over more pain relief.

  5. Ibim
    Reply

    For a list of doctors who offer ketamine infusions for depression, see the Ketamine Advocacy Network website, http://www.ketaminenetwork.org. It also hosts a discussion forum for ketamine patients, and prospective patients.
    Several of the comments on this page are badly misinformed. I’m not going to argue each point, but do want to point out the following:
    1. The antidepressant effect depends on the ketamine being delivered to the brain at a very precise rate, without being metabolized by the body first. This is the reason IV infusion is used in virtually all the published studies, and by most of the clinical practitioners. Ketamine delivered via an IV infusion is 100% bioavailable, meaning none of it is metabolized by the body before it reaches the brain, and the IV allows it to be delivered at a very precise rate. Both of these are necessary to achieve the full antidepressant effect. If you were to take ketamine orally, about 84% of it will be quickly metabolized into a substance called “norketamine”. When the remaining 16% of the original ketamine reaches the brain, it will be accompanied by a large amount of this norketamine. And the rate at which these combined substances arrive in the brain is quite different than a controlled IV drip. This scenario will not not produce the same antidepressant effect. Nor will intramuscular injection, or intranasal. That’s not to say those routes of administration are useless, because every patient is different. But IV is far and away the most effective and reliable means to achieve the antidepressant effect.
    2. The doses used in depression treatment are far below any anesthetic or recreational dose. The patient never loses consciousness. But yes, many experience a dissociative effect. Most find it tolerable if not pleasant. The most recent paper from NIH (Zarate, et al) published this month demonstrates a correlation between the intensity of the dissociative effect and the resulting antidepressant outcome. In short, the stronger the dissociation, the more likely the patient will experience depression relief in the days/weeks following. (Again, this is in the context of a tiny dose delivered very slowly via IV.)
    3. Giving a benzodiazepine in conjunction with an infusion will reduce or even eliminate the antidepressant effect.
    4. Ketamine is not physically addictive.
    5. The mechanism of action is fairly complicated. Delivering a tiny dose of ketamine at a precisely controlled rate, while avoiding first-pass metabolism, is only the trigger for a cascading sequence of events. Those events culminate in the rapid rise of brain-derived neurotrophic factor (BDNF) in the brain, which in turn stimulates the rapid re-growth of neural dendrites that have previously atrophied. In other words, it causes new synapses to grow. To understand the underlying science, go to PubMed and read the papers by Carlos Zarate, John Murrough, Ron Duman, Gerald Sanacora, Dennis Charney, John Chrystal, and others.

  6. Pam Pudewa
    Reply

    As a Registered Addiction Specialist I am very alarmed at this article. Ketamine is highly addictive. If you recall, Sigmund Freud “pioneered” the use of Cocaine to treat depression. It works really well, for a few minutes. But the crash afterward and the power of the addiction, (addiction or dependence is characterized by tolerance or the need for a higher dose to produce the same effect, and withdrawal or negative physical reaction with the stoppage of use) need to be carefully considered before ketamine or any other drug is released into the market for legal prescription.
    Prescription drug abuse is at an all-time high. I cannot tell you how many clients I see who are addicted to legal drugs, and their problems are no better than those of a street junkie looking for a fix.

  7. ifeoma
    Reply

    It needs monitoring.

  8. TW
    Reply

    What are the side effects? Is it worth it in the long run ( especially for the kidneys and liver)?
    PEOPLE’S PHARMACY RESPONSE:
    Most of the research has been done on injectable ketamine, when used as an anesthetic. That makes it a bit hard to generalize to this new area of research.
    Here are some recognized Ketamine Side Effects:
    Excessive saliva production
    Nausea, loss of appetite
    Changes in heart rate and blood pressure
    Uncontrollable eye “waggles,” double vision
    Confusion/hallucinations/delirium/fearfulness
    Irregular heart rhythms
    Dizziness
    Fasciculation, uncontrollable muscle twitches
    Allergic reactions including anaphylaxis
    Insomnia

  9. PR
    Reply

    Reading this post would lead me to believe as an Anesthesiologist I should use this drug all the time, EXCEPT in many patients it causes a dysphoric reaction when used intravenously. We must use a drug like valium to try and prevent the dysphoric reactions. You do an injustice to your audience by not informing them of that as you make it sound like it only happens when taken orally. Every drug has a side effect, yet you mention none when used this way.
    So if I was a patient with clinical depression why would I want injections that may have side effects so often as this. Unlike chemotherapy there is no end point when using this drug. Perhaps you should also publish the rest of the story.
    PEOPLE’S PHARMACY RESPONSE:
    Dear Dr. P.R.
    Thank you for your comments. You are absolutely correct that ketamine does indeed have some serious “dysphoric” side effects. The dissociative anesthesia is quite uncomfortable for many people, which is why recovery from anesthesia requires care…and sometimes a drug like diazepam (Valium) to reduce the anxiety associated with the unusual “return to body” experience.
    That said, this drug is revolutionizing hard-to-treat depression. We know of no antidepressant (or other treatment for that matter) that has produced such fast results (hours vs. weeks) in selected patients. When someone is in a deep depression and suicide seems like the only solution, we need a fast-acting option and ketamine may be it.
    There is also the fact that hundreds of thousands (perhaps millions) of people are using Special K as a “club drug” on a regular basis. We don’t condone this activity, but clearly a lot of people are taking it orally in a social context. We have been puzzled why investigators have not contemplated an oral route with ketamine in hard-to-treat depression.
    Ultimately, we hope that researchers uncover the mechanism of action of ketamine and create a drug that will not have the dissociative anesthetic properties or other side effects of ketamine. The sooner we can harness the unique action of this old drug in the treatment of severe depression the better, in our opinion. Do you not agree?

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