Ketamine: A Miracle Drug for Depression, or Not?

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A team of researchers funded by the National Institutes of Health (NIH) recently discovered why the drug ketamine may act as a rapid antidepressant.

Ketamine is best known as an illicit, psychedelic club drug. Often referred to as “Special K” or a “horse tranquilizer” by the media, it has been around since the 1960s and is a staple anesthetic in emergency rooms and burn centers. In the last 10 years, studies have shown that it can reverse — sometimes within hours or even minutes — the kind of severe, suicidal depression that traditional antidepressants can’t treat.

Researchers writing in the August 2010 issue of Archives of General Psychiatry reported that people in a small study who had treatment-resistant bipolar disorder experienced relief from depression symptoms in as little as 40 minutes after getting an intravenous dose of ketamine. Eighteen of these people had previously been unsuccessfully treated with at least one antidepressant medication and a mood stabilizer; the average number of medications they had tried unsuccessfully was seven. Within 40 minutes, 9 of 16 (56 percent) of the participants receiving ketamine had at least a 50 percent reduction in symptoms, and 2 of 16 (13 percent) had full remission and became symptom-free. The response lasted an average of about a week.

In a small 2006 NIMH study, one of the first to look at ketamine for depression, 18 treatment-resistant, depressed (unipolar) patients were randomly selected to receive either a single intravenous dose of ketamine or a placebo. Depression symptoms improved within one day in 71 percent of those who were given ketamine, and 29 percent of the patients became nearly symptom-free in a day. Thirty-five percent of patients who received ketamine still showed benefits seven days later.

In the most recent study, reported online in the journal Nature in May 2016, researchers discovered that a chemical byproduct, or metabolite, is created as the body breaks down ketamine. The metabolite reversed depression-like behaviors in mice without triggering any of the anesthetic, dissociative, or addictive side effects associated with ketamine.

“This discovery fundamentally changes our understanding of how this rapid antidepressant mechanism works, and holds promise for development of more robust and safer treatments,” said Carlos Zarate, MD, of the National Institute of Mental Health (NIMH), and a study coauthor and pioneer of research using ketamine to treat depression. “By using a team approach, researchers were able to reverse-engineer ketamine’s workings from the clinic to the lab to pinpoint what makes it so unique.”

In response to the Nature report, Sara Solovitch of The Washington Post wrote that “experts are calling [ketamine] the most significant advance in mental health in more than half a century.” She reported that many academic medical centers, including Yale University, the University of California in San Diego, the Mayo Clinic, and the Cleveland Clinic, have all begun offering ketamine treatments off-label for severe depression.

It all sounds too good to be true, right?

The Drawbacks of Ketamine

The predominant drawback of ketamine is the lack of data.

There haven’t been enough clinical trials on the drug to assure its safety, and there’s a lack of information on the long-term effects of its use.

Ketamine’s effects are also short-lived. To be used as an effective antidepressant, it would need to be administered regularly, which leads to concerns about addiction, tolerance, and, again, long-term effects. The data that we do have on long-term use comes from people who have taken ketamine recreationally, as well as those who have used it to treat chronic pain. One 2014 study published in the British Journal of Clinical Pharmacology included among possible side effects psychedelic symptoms (hallucinations and panic attacks), nausea, cardiovascular stimulation, memory defects, and bladder and renal complications.

Still, the drug holds promise for uncovering new ways of treating depression and offers hope for the most severe and complicated mood disorders that baffle psychiatrists today.

“Unraveling the mechanism mediating ketamine’s antidepressant activity is an important step in the process of drug development,” said Richard J. Hodes, MD, director of the National Institute on Aging, about the most recent NIH study. “New approaches are critical for the treatment of depression, especially for older adults and for patients who do not respond to current medications.”

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Photo: Julia Hiebaum/Alamy

Originally published on Sanity Break.

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22 thoughts on “Ketamine: A Miracle Drug for Depression, or Not?

  1. As a clinical psychologist and long sufferer of depression, I arranged for a series of Ketamine treatments in my office. I knew an anesthesiologist and we set up the treatment protocol based on the research I had reviewed. During each intravenous procedure I felt an intense, what I would describe as a morphine rush. Feeling hot and almost delusional. I kept myself calm, but I wonder how that might effect some people, especially those with a more anxious disposition.

    I had 6, bi-weekly treatments and noticed no clinical benefits whatsoever. There are certainly different kinds of unipolar depression, so generalizing treatments can be problematic. I have responded “OK” to SSRIs over the years, so I would say I am not too atypical. My depression has morphed into a kind of drab dysthymia, which affects my motivation and general ability to enjoy life.

    So I am not convinced by Ketamine treatment. Studies are ongoing, (for over 5 years) and my best guess is that it will remain a back up for certain kinds of depressive conditions. However, we are a long way from figuring these neurobiological variations out.

    1. It’s unfortunate that intravenous ketamine was not effective for you, but I’m sure that your research told you that it has been effective for quite a large number of people. As a clinical psychologist you must also know that judging a treatment of any kind, based on a single patient’s experience is not good science.

      1. Hi Joseph,

        I think I actually addressed your comment in my posting. Yes, (as a clinical psychologist) I am aware that this is my personal response! My whole point is to share with people that this did not work for ME and to raise the very important dilemma that there are multiple different kinds of depression (still emerging) and that we are a long way in research from identifying these brain states. Thus, it is still very hard to predict who will respond to what medication.. Even genetic typing is proving limited in predicting depression medication response.

        I think the whole point of the Blog is to share our personal experiences. This was mine,

          1. It did nothing for me. Clinically we still have very mixed reviews on Ketamine. Some psychiatric researchers I have spoken to are very skeptical that it will ever be useful as an actual treatment. Some in other medical centers seem more positive. Truth is we have years of trials left before (and if) it should go through arduous the FDA approval into general use. Not to mention the problem of addiction and long term use etc. . .

          2. Janssen has been doing trials of an esketamine intranasal spray for a few years. They anticipate having FDA approval in 2019.

            I’ve been doing very extensive research on ketamine. I would say that the majority of people who have tried or are using ketamine and have reported their experiences online, have seen an improvement in their symptoms. All the studies I’ve read report a very high remission rate. This does not last, but neither do any of the other drugs prescribed for depression. I don’t agree that ketamine, under the doses that it is given to treat depression, poses a significant overdose or addiction risk. That’s just not supported by research.

          3. Hi Joe

            Naturally we could go all day about the mixed reviews on K. You have not tried the drug I assume. You have not mentioned your struggle with depression? This always interests me, This is as I mentioned is a key issue in trying to find goodness of fit in medicine. Age of onset, kind of symptoms etc. . I have responded well over time to SSRIs, never had a manic episode, early onset. How have you responded?

          4. I was diagnosed with dysthymia in 1989. Then, in 2010 the diagnosis was changed to MDD. I have tried at least twenty different medications as well as ECT. I’ve undergone several counselling formats. I have not tried ketamine because it is very difficult to find in Canada.

            I don’t believe that the reviews for ketamine are very “mixed”. According to my extensive research, the majority find relief for their symptoms. Ketamine does not appear to “cure” depression, so ongoing treatment is likely required, but that is no worse than the history of other antidepressants.

          5. Joe,

            Lets leave the Ketamine (I could show you evidence and I know you could counter). No point right now. Clearly you are hopeful and that is fine, I have shied away from the ECT but often thought about it. over the years. At this point in my life I have turned to my belief (Catholic) and the role of suffering in life. Job has been an inspiration for me and I have written about him in this context. These things, family and a good relationship with a seasoned psychiatrist. I have learned not to rely on medicine too much but certainly get help from this from time to time. For those like us
            who have this long term pattern, it is a tough journey. For now, let’s see how things pan out with Ketamine and several other meds/procedures in development!

  2. I have been waiting anxiously for a ketamine clinic to open up near me. It seems like a intervention that holds some promise at least for people like myself who have not responded to SSRIs/SNRIs, mood stabilizers, tricyclics, or could not tolerate the side effects of anti-psychotics. I’ve also had a full 36 treatment series of rTMS which helped a lot at first but the effects gradually wore off over time. I’m still not as bad as I used to be, but my anxiety has also increased as well as my rumination and ability to get through a day of work at times. I’ve never been in remission. I wonder if the ketamine might help get me closer if only even for the short term.

  3. I’ve been using intranasal ketamine for about 2 years. It’s been a complete game changer for me!
    It is bar none the most effective and cleanest antidepressant I’ve ever used. I take a relatively small dose about once every 5-6 days and have zero side effects except for five minutes of a weird taste in my throat from a bit of the nasal spray reaching it. It’s effective within about 24 hours, and I’m good for several days. It’s allowed me to cut my regular lamictal dose in half and drop another medicine I was on. I feel so much better overall with less medication in my system, and my depression is under better control. I’m so grateful my doctor was interested in trying out the nasal spray on some of his treatment resistant folks – several of us are doing very well with it.

    1. Hi Rockgal,

      That’s great that you have found benefit. Could you describe the symptoms of your depression (ie Bipolar, or unipolar) and the age of onset of symptoms. I think it will help others gauge whether your symptoms are similar. I had a non response to IV K and nasal, but they are finding new ways of dosing the drug for more efficacy.

      Thanks

      King Crimson

      1. Hello,
        I’ve been wanting to try K for a few years now, but can’t find anyone who administers it here in NC. Duke University Med. Center was supposed to be getting closer to getting a clinic, but no word yet. Where are you receiving treatments?
        Thanks!

        1. Hi,

          I am a developmental psychologist, so being in the health field I actually had an MD prescribe it and paid to have a anesthesiologist friend administer it . To be clear, it did nothing to affect my mood after 6 treatments. I think we are a long way from knowing what works for what kind of mood disorder. Really it’s still trial and error. The nose spray had similarly no effect. That’s why I urge people on this sight to describe their symptoms and age of onset when talking about medication. That helps others who may be considering this or that treatment.
          For me, onset 3 years of age. Long term dysthymia, a few clinical episodes in my 20s (now 50+).

          Take Care

          Rich

      2. Hi King Crimson (Richard),

        I have unipolar depression, although I seem to have better success with the medications used for bipolar disorder (e.g., Lamictal). My depression probably came and went in milder forms earlier in my life, but I got an official diagnosis around 31 or 32. I’m considered treatment resistant. SSRIs either poop out or don’t help, I can’t tolerate tricyclics or Effexor, and Cymbalta made me worse. And so it goes.

        I agree it’s definitely at a stage where psychiatrists are just starting to get some clinical experience with the nasal spray. I have two friends who have tried intranasal ketamine. One found it effective, and it did nothing for the other. Also, from what my doctor said about it working for about half of this patients who’ve tried it, it almost seems binary. It either helps someone a lot, or it does nothing. It was clear right away (like within 24 hours) that it was going to be effective for me, and it took a month or so of experimenting with dosage and frequency to find out what felt the best.

        Anyway, I hope that helps!

        Rockgal

    2. Rockgal,

      It very interesting that some folks have a excellent response to ketamine and others no response.

      For the last year or so I have worked providing anesthesia for oral surgery patents using ketamine. I am thinking about doing research in this area. I have seen that people vary greatly in their response and I wonder if we can determine which people are most likely benefit from this.

      Thank you for sharing your experience with us.

      sincerely,

      CJS

  4. Hi everybody. My name is scum and i am poly-junkie. Thing is that i stop to use opium one month ago and alcohol 1 week ago(thanx to k alcohol became super disgusting thing in my life) but i have big problems with neuro mediators. When took k i feel happy and super smart. My friends who are educated properly r’e reaLy interested to listening me. But there is big side effect in next day. My depression became hmmm… How to describe it?! It gets harder but calmer. I mean i cant speak with people who asks too many questions(gettin a bit rude and saying them that they need think a bit and they will find answer to their question. Im living on street and squats about 4 years now. I know that i am scum and i need serious help with my mental state. But i am self educating all my life from books and internet.
    Ok. Thing is i took yesterday like in 8 hours half gram of k powder (liquid were prepared on pann near to me, clean product for sure.) Every hour. Today i fell shit but calm. I dont see my future normal. I think i wil! Die soon from kidny or heart problems. Maybe someone can help me with advice? I tried sertralina teva 2 years ago and it was a bit strange but effective. Now i tried it again and when i stop course everything became senseless. I dont know what to do. If someone can help with advice ,than write me please. Dderums@gmail.com.
    P.s. pardon for my english. Its not my native language. Wish to everybody be strong no matter what!

  5. I am 78 years old,MDD patient for more than 30 years.was treated with many drugs ,only Paroxetine helped for 6 years.even Ect was beneficial for about 11 years.Status present:I need 24 hours my husband help but both of us want to try K treatment,as chance for a better quality of life.I live in Israel,where this treatment is not available.

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