Major Depressive Disorder & Ketamine | Fanning the Flame of Hope

Major Depressive Disorder

Hope is a matter of spirit. And it sure as heck helps to have some cold, hard facts to fan the flame. Ketamine has rushed to the possibilities-forefront of major depressive disorder treatment. And I’m here to tell you why, including the very latest…

Tons of flame-fanning to do, folks, so we’re gonna’ jump right in. Good to go? Okay, let’s start with a ketamine thumbnail.

What is Ketamine?

Seems a research team from the Icahn School of Medicine at Mount Sinai (NY) has the first controlled evidence that an intranasal ketamine spray produced an unusually rapid antidepressant effect. That would be within 24 hours. And it proved safe, with minimal dissociative effects or changes in blood circulation.

As you may know, ketamine is used in human and veterinary medicine. In us human-types, it’s used as an anesthetic, as well as for sedation, pain, bronchospasm, complex regional pain syndrome, and more. ‘Course, it’s also used recreationally (“Special K,” etc.) at doses as high as 100 times the typical medical dose. Ketamine produces a dissociative state, with occasional accompanying hallucinations (hitting the “K-Hole”).

The bulk of ketamine’s impact comes from its work as a NMDA glutamate (neurotransmitter) receptor antagonist (blocks or inhibits action). And that’s what puts it at the possibilities-forefront for the treatment of major depressive disorder.

It was discovered in the early-2000s that ketamine put the kibosh on unipolar and bipolar depressive symptoms within two hours of administration. And the effect lasted several days. ‘Course, administration issues and nasty side effects formed a major practicality barrier. Nonetheless, the candle had been lit, and research brainiacs haven’t given up on how to make ketamine a practical treatment for depression.

What’s the Latest on Ketamine and Major Depressive Disorder?

Just three months ago, the results of a hopeful study were published in Biological Psychiatry. Seems a research team from the Icahn School of Medicine at Mount Sinai (NY) has the first controlled evidence that an intranasal ketamine spray produced an unusually rapid antidepressant effect. That would be within 24 hours. And it proved safe, with minimal dissociative effects or changes in blood circulation.

According to principal investigator James W. Murrough, MD…

One of the primary effects of ketamine in the brain is to block the NMDA glutamate receptor. There is an urgent clinical need for new treatments for depression with novel mechanisms of action. With further research and development, this could lay the groundwork for using NMDA targeted treatments for major depressive disorder.

Going forward, the team hopes to examine the mechanism of action, dose ranging, and learn more about how ketamine works by using functional brain imaging.

So, Dr. Murrough mentioned laying the groundwork for using NMDA-targeted treatments for major depressive disorder. I’ve written about GLYX-13 several times here on Chipur. Being developed by Naurex, it also influences NMDA.

Check this out! Data from GLYX-13s Phase 2 clinical trial report a single dose produced statistically significant reductions in depression scores in patients who had failed treatment with current antidepressants. And these reductions were observable within 24 hours of administration, lasting for an average of seven days.

Finally, GLYX-13s antidepressant effect was some 200% greater than that seen with most existing antidepressants after four to six week’s use. Oh, it was well tolerated and didn’t produce even one schizophrenia-like side-effect, often seen with other NMDA receptor modulating agents.

Great news! The FDA has fast-tracked GLYX-13s development.

Okay, now for something published in this month’s issue of Anesthesiology. Researchers from the Intramural Research Program at the National Institute on Aging (US) have identified a compound, hydroxynorketamine (HNK), that may treat symptoms of depression just as effectively and rapidly as ketamine, without the nasty side effects. HNK is one of several different compounds produced when ketamine is metabolized.

From senior investigator Irving Wainer, PhD…

The clinical use of ketamine therapy for depression is limited because the drug is administered intravenously and may produce adverse effects such as hallucinations and sedation to the point of anesthesia. We found that the HNK compound significantly contributes to the anti-depressive effects of ketamine in animals, but doesn’t produce the sedation or anesthesia, which makes HNK an attractive alternative as an antidepressant in humans.

Amazingly, the research team found HNK, like ketamine, not only produced potent and rapid antidepressant effects, but also stimulated neuro-regenerative pathways and initiated the regrowth of neurons in rats’ brains. HNK also appears to have several advantages over ketamine in that it is 1,000 times more potent, does not act as an anesthetic agent, and can be taken by mouth.

So how ‘bout that ketamine?! Or should I say those NMDA receptor antagonists.

That’ll Do It

You know, when it comes to remedies for major depressive disorder, panic attack symptoms, PTSD, stress, etc., I prefer to bring you immediately available goodies.

But I couldn’t resist these ketamine/NMDA developments. I believe the prospects are hot, and I’m thinking “on the shelves” won’t be years and years away. And, by the way, isn’t it heartening to know research folk are working hard to bring relief and healing?

Yeah, fanning the flame of hope….

image credit “Flame from a Burning Candle” by MarcusObalOwn work. Licensed under CC BY-SA 3.0 via Wikimedia Commons.

All sorts of hopeful Chipur titles for your eyeballs. Ya’ gotta’ check ’em out.

  • Cathy | Treatment Talk July 22, 2014, 5:43 pm

    Great news and more hope for those suffering from major depressive disorder, panic attack symptoms, PTSD, stress, etc. It’s nice to know that you are on the cutting edge of the latest developments. Thanks for sharing, Bill.

    • Chipur July 22, 2014, 5:52 pm

      Thanks, Cathy. And thank you for stopping-by. Yeah, this one is pretty huge. Lots of new meds and prospects come and go, but I have a good feeling about the ketamine/NMDA thing. What really excites me is we’re now working with glutamate, as opposed to serotonin, norepinephrine, dopamine. Hey, let’s see what pans out, but I’m holding out hope for this baby.

      Keep comin’ back, k?


  • Megan July 23, 2014, 4:19 am

    Is there anything in the works for anxiety? I feel like they’ve put on a big Xanax label on it and sealed the file.

    • Rich July 23, 2014, 7:34 am

      Megan, ketamine is very effective on anxiety. I’ve had depression since 1978 and started getting ketamine infusions in 2012. For me anxiety is the worst part of my depression and makes life unbearable. I tried many SSRIs but they never helped any of my symptoms, and usually made everything worse. I took benzos for years and they helped the anxiety for a few hours at a time. But after my first ketamine infusions the anxiety disappeared for two full months. The relief feels very different from a benzo. With benzos it feels like there is something on top of the anxiety that is holding it down. I feel medicated. But with ketamine the anxiety simply evaporates. There is no sense of being medicated. The anxiety vanishes with no residue. The only thing left is the personality I always knew I had but could never express. I get infusions about every two months now to keep it under control.

      • Chipur July 23, 2014, 7:46 am

        Man, Rich, thank you for stopping-by and contributing. Would you mind providing some detail on how you came by ketamine, as well as any other info you think may help us?


      • Rich July 23, 2014, 12:19 pm

        Sure. I’ve talked to a lot of other ketamine patients and depression sufferers and I think my story is pretty typical. I was abused continually between the ages of 3 and 17 and grew up in a constant state of fear. The constant anxiety grew into full blown depression by my early 20s. I tried every depression drug and treatment known to science. Except ECT, I’d rather let depression kill me than become an ECT zombie and lose my memory. And many years of psychotherapy. The benzos helped a few hours at a time but only with the anxiety part. But there’s only so much pain a person can endure and eventually my life was reduced to a 24×7 struggle to avoid suicide. I never heard of ketamine but then someone told me about a study at the National Institutes of Health. I spent 3 months there as a lab rat and probably have one of the most highly imaged brains in the world now. They gave me dozens of high power MRIs, magnetoencephalograms, EEGs, and more. I got a ketamine infusion there and after a few hours everything was different. No more anxiety. No self loathing. I could experience emotions and feel happiness. I could sleep through the night and feel rested. Now I see Dr. Glen Brooks in NYC about every two months for maintenance infusions that keep my depression under control. I highly recommend him. The website that Ibim mentioned is a good resource, the guy that runs the ketamine advocacy network knows a lot more than me but the website is hardly ever updated. I also know some people where ketamine did not work but their depression was different from mine in that theirs wasn’t caused by long term stress. Ketamine works for bipolar and PTSD too.

      • Chipur July 23, 2014, 3:20 pm

        Great story and info, Rich. I’m so pleased to have this available for readers. Thank you…


      • Nancy Frye Peden July 24, 2014, 1:22 pm

        I am so glad to see this testimony, thank you, Rich and thanks Bill for the article.
        I tried to get into the NIH studies but no one here in “progressive” Monterey, CA or in CA, was doing it.

        I especially would love something that would help my life long self loathing and my inability to sleep on my own. What a miracle these would be in my life!

        Thanks also Ibim for the ketamine network site address. I signed the petition long ago but maybe I will go there and see if I can sign it again.

        This needs to be available. I sent the article to my psych….wonder what he will say. He is open to many things but works in a very strict hospital (sigh).

        Thanks again all.

      • Chipur July 24, 2014, 3:18 pm

        More than welcome, Nancy. Glad you stopped-by…


      • Clay October 8, 2014, 9:35 pm

        I’ve been researching. Anxiety is definitely the worst part of my depression. All the talk is about MDD, but how exactly do you think it worked on your anxiety? Just looking for thoughts and experiences. Thanks for your time.

      • Chipur October 9, 2014, 10:06 am

        Appreciate your visit and comment, Clay. In addition to Rich’s contribution, check this out


      • Clay October 11, 2014, 10:45 pm

        Great site Bill. And thanks for the link. It looks very promising. My question now is, do you think for those who have the ‘anxious depression’, where anxiety seems to be a daily prevalent symptom, that the action of ketamine hits anxiety to where the happiness lifts depression as well? Does that make sense. I think I read about a study where it said those with anxious depression seem to respond better. Any thoughts?

      • Chipur October 12, 2014, 1:38 pm

        Glad you found the material at the link meaningful, Clay. Yeah, I think what you’re asking does make sense. I think ketamine biochemically hits both anxiety and depression. And I believe the depression would get a double-hit because if the anxiety decreases – heck, that would make anyone’s mood lift. Right? And as we’re chatting ketamine, let’s not forget this med that’s in the pipeline, because it was developed based upon the positive impact of ketamine on depression


      • Clay October 12, 2014, 4:47 pm

        I have seen that Bill. GLYX-13 looks like a great drug. I believe Naurex has a second drug coming behind it, called NRX-1074. It’s supposed to be an even stronger version. I like your site. It’s very informative. You’re doing a great job. I wish I could talk to Rich, or anyone else wok have had success with Ketamine as far as the anxiety portion of it is concerned. There is so much I want to know and learn and see if I can apply this therapy to myself.

      • Chipur October 12, 2014, 6:37 pm

        …and in the meantime, don’t lose the forest for the trees. Step away from that battlefield and live your life, k?


      • Clay October 12, 2014, 7:13 pm

        You got it Bill. Keep up the good work.

    • Chipur July 23, 2014, 7:43 am

      Appreciate your visit and comment, Megan. And how ’bout Rich’s reply?!

  • Chipur July 23, 2014, 7:57 am

    Nice resource, Ibim. Thank you…


    • Megan July 23, 2014, 9:15 am

      Thank you, Rich and Ibim. Closest doctor is in Atlanta,

  • Chipur July 23, 2014, 9:33 am

    Important! In a comment, Ibim provided a link to Rich resource, so be sure to check it out. Even a petition available to sign.


  • Chipur July 23, 2014, 3:16 pm

    Always say – be careful with forums. Just never know what you might see, and who knows about reliability. Just sayin’. Dunno re doses/panic attacks or cost…


  • Beth Wilson July 24, 2014, 5:14 pm

    Hey Bill! Wow! This is great news with the potential to really change the ways in which clinicians and professionals treat folks. So grateful for you and the ways you simplify the info for brains like mine!

    • Chipur July 24, 2014, 6:14 pm

      And I’m grateful to you and others for stopping-by and contributing. Means a lot. Yes, I believe the potential for relief here is great. Glad I could make the info easier to digest, though I’m thinkin’ your brain is mighty strong! ‘Preciate you, Beth…


  • Dr. Herby Bell July 26, 2014, 5:56 pm

    Always pleased by the places you go, Bill. An open inquiry to what actually helps as Dr. Carrie Wilkens of the Center for Motivation and Change might say, “finding hope in hell.” Also like the idea that we can revisit and refine our thinking as human beings. Special K misuse and abuse at one end of the spectrum and a whole new frontier of hope at the other with this powerful agent called Ketamine. Most interesting and appreciated slant here. Thank you!

    • Chipur July 27, 2014, 12:38 pm

      Ah, always venturing into the supposed unknown. Thing is, though, most of what I come up with is, in fact, known – just needs more publicity. And so it is with ketamine and the NMDA receptor neck of the woods. Perhaps if we push hard enough we’ll get even more research and regulatory engagement. Ya’ think? I’m always glad you stop-by, Herby. Having someone with your credentials and background say positive things here brings Chipur credibility. It’s appreciated, my friend…


  • george bowden July 22, 2017, 1:26 pm

    So it’s been three years. Have there been no further developments on the efficacy of HNK?

    • Chipur July 22, 2017, 10:26 pm

      Interest in HNK continues to run high, but it’s still being tested (NIMH, I believe) for how safe it would be in human trials. Once it’s okay’d, perhaps it will be “fast-tracked” through the FDA approval process. Interesting: I’ve seen HNK group buys being organized online. Seems those in charge have found chemical companies willing to synthesize it. (Of course, I’m not recommending.)

      Wish I had better news for you, George. Thank you for visiting and asking…