a sad and depressed woman crying

Doctors are wrestling with the ethical and legal challenges of prescribing ketamine for severely depressed or suicidal patients. The drug may help some people, but doctors worry about the possibility ketamine could be abused or cause side effects (BMC Medical Ethics, Jan. 14, 2016).

That said, severe depression is a life-threatening condition. Suicidal thoughts are a common consequence, especially since there are no quick fixes for this kind of depression. Most approved antidepressant medications take several weeks to start working.

That’s why there is such interest in the fast-acting anesthetic ketamine. An article in Molecular Psychiatry (Jan. 19, 2016) notes that ketamine “elicits antidepressant actions in hours” and that this rapid effect has been transformative.

This reader tells a fascinating story:

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 been confirmed by a surprising number of small studies. One published in the journal Psychological Medicine (online, Aug, 2015) reports on a randomized, controlled trial of ketamine in 24 suicidal patients. Half were given ketamine and the other half received a different anesthetic called midazolam (as a placebo). Within two days the people who received ketamine had a significant reduction in suicidal thoughts compared to midazolam. The researchers concluded:

The current findings provide initial support for the safety and tolerability of ketamine as an intervention for SI [suicidal ideation] in patients who are at elevated risk for suicidal behavior. Larger, well-powered studies are warranted.”

Research published in the Journal of Psychopharmacology (online, April 3, 2014) 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.

Fast Antidepressant Action:

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.

Another study conducted by scientists at the National Institute of Mental Health (Journal of Psychiatric Research, Nov. 2014) found that: Ketamine infusion was associated with significant reductions in suicidal ideation compared to placebo, when controlling for the effects of ketamine on depression and anxiety.”

The History of Ketamine:

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.

Street Names for Ketamine

Caution about ketamine results in part because of its negative reputation as a club drug. The main street name for ketamine is Special K. Other names include “K,” “Cat Valium,” “Kit Kat,” “Super C” and “Green.”

When taken orally, the drug produces a “dissociative” effect that some describe as a detached or distorted sense of reality. 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.

Some investigators are studying the possibility of administering ketamine in a nasal spray (Intranasal Drug Delivery on INDD). A review in the Journal of Clinical Psychiatry (May, 2015) discusses this possibility.

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.”

Should you want to learn more about ketamine research in treating suicide, here is another helpful link.

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.

Revised January 21, 2015

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  1. Marie

    As a mother whose son who took his life at age 29, almost 5 years ago, related to chronic severe depression, I would love to see this drug considered more seriously for treatment of depression and chronic suicidal ideation. As far as it’s possible addictive qualities given in a medical setting by a physician, if what the patient would potentially be addicted to would be some happiness and a desire to live, instead of deep hopelessness and the desire to die, then to me, it’s worth the risk that the patient might get addicted to life! I would love for my son to have had a drug that had a positive effect on his depression. His bright, creative intelligence wasn’t enough to keep him out of the depths of despair. He had been prescribed most of what was available from psychiatric providers, with the meds leaving him feeling drugged and not like himself. Sadly, this is why many patients quit taking their medications or become “non-compliant”. Mental pain is as devastating as physical pain. I hope that this drug can be researched and used appropriately asap. The suicide rate in the US is alarming. Go to a funeral home and ask them about the number of suicides they’ve taken care of over the last 5 to 10 yrs. It’s time to take action. Thanks to People’s Pharmacy for bringing ketamine to light.

  2. Yolanda

    It seems that this should be evaluated on an independent basis. Neurological side effects are often looked over,but can be quite troubling.

    • Dee
      Gulf Coast Florida

      I am sorry to hear about your son. I did not know him but I lost a son he was 37, Side effects of a approved drug killed him. It is such a thin line when you have such severe depression. I have managed to live so far. People who have never had to live or I should say exist with this illness will never understand. People with MDD do not live. The essence of life is turned to rote mannerisms and hollow souls attempting to connect somehow to something that is so far from their grasps. I am alone. I have no insurance. I am 59 and I pray I will have the opportunity to live before I die. I would love to try this. It makes me feel worse knowing there is something that could make a difference and I can not have it because I do not have the money for the extreme price the clinics charge. The drug is cheap. I don’t understand. I would like to see Ketamine readily available and affordable.

  3. Laurel

    Can Ketamine be used for a few weeks while another, more standard/oral antidepressant is added then the ketamine amount be reduced? This would seem to offer the benefit of the quick acting drug to prevent a catastrophic event from happening until the other drug kicks in.

  4. Daniel M.
    Phx. Az.

    I feel so frantically discouraged with someone in control of my body,mind, and ability to feel well enough to re-join life!! Please write and keep on writing about this serious topic. The negative view people who are not affected. Depressed people go hospital to hospital and get drugs that you know won’t work I v ketamine is the only med that helps keep me steady so as not to jump off a bridge. I use IVKetamine.

  5. Ppbear1
    Lewisville, TX

    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.

  6. Laura P.

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

  7. jale

    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:

    • Anonymous

      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. )

  8. Helen M

    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.

  9. Ibim

    For a list of doctors who offer ketamine infusions for depression, see the Ketamine Advocacy Network website. 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.

  10. Pam Pudewa

    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.

  11. ifeoma

    It needs monitoring.

  12. TW

    What are the side effects? Is it worth it in the long run ( especially for the kidneys and liver)?
    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
    Irregular heart rhythms
    Fasciculation, uncontrollable muscle twitches
    Allergic reactions including anaphylaxis

  13. PR

    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.
    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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