Ketamine for Treatment Resistant Depression

I do what I do because I love helping people alleviate their suffering and to improve their quality of life. That is why I love going to work every day.

David J. Miller, RPh, PhD, FIACP, FACA Owner and Chief Formulation Scientist

David J. Miller, RPh, PhD, FIACP, FACA
Owner and Chief Formulation Scientist

Recently, I received a telephone call from a friend of mine in Utah. He expressed deep concern for a friend of his since high school who had been suffering from severe, treatment resistant depression for much of his adult life. Ever since high school, Matt looked up to his friend Jim for many reasons. Jim is an extreme athlete, is financially secure with a beautiful home, has model good looks, has a loving, caring, wife and wonderful friends. For some reason, however he said he was constantly unhappy and “struggling” with himself. Matt stated that lately Jim seemed to be taking an even greater downturn in his depression and started “joking” about possibly ending it all. Matt started worrying that Jim may contemplate doing something tragic.

Jim had tried every anti-depressant imaginable from SSRIs like Prozac to SNRI’s like Effexor to Tricyclic agents like Elavil. To date, despite extensive counseling, no single drug or combination of drugs had worked very well for Jim; at best, the combined therapies arguably kept Jim grounded so that he can be functional. Further, the meds Jim was taking had some side effects that often were too embarrassing to talk about. Consequently, Jim’s life still was filled with anxiety, hopelessness, constant feelings of negativity and self-doubt, a weight or pressure if you will, a lack of any pleasure and an increasing general inability to function in life. It all represented a tremendous strain for Jim both at work and on his marriage. Oftentimes, Jim would express anger and frustration about how poorly he was treating his wife. He credited this treatment to his depressed feelings, adding guilt to his anxiety and negativity toward life.

Matt had read numerous articles on the use ketamine for the treatment of treatment resistant depression and asked me what I thought. Ketamine, an FDA approved drug for anesthesia, is well known as the “Special K” psychedelic party drug which has been abused in our culture for decades leading to potential long term adverse side effects of its users. Ketamine is a schedule 3 (III) drug defined by the Controlled Substances Act.

Despite this, I had been very excited about the off label use of ketamine for depression since Dr. John Mulder introduced me to the topic about a year ago. When used under well controlled doses much lower than that abused illegally, I have seen positive results in my own practice with some patients calling the results “life changing.” Matt asked me if I thought ketamine therapy could help Jim. I did not know Jim or his condition, but the scientific literature surrounding ketamine IV infusions for treatment resistant depression demonstrates about an 77% effectiveness with a low side effect profile.

Fast forward a couple weeks: Jim has received three infusions of ketamine. I received a text from him last night stating that he was “Pretty amazed-really quite astonished!” and he reported to Matt that he was “psyched” and “stoked” to describe how both he and his wife felt about his ketamine treatment. Ketamine seems to be working to treat Jim’s depression when all other treatment modalities have failed him.

What is the science behind ketamine and alleviating treatment resistant depression? Much of it is not completely well understood. Ketamine is believed to be an antagonist of a neurotransmitter called N-methyl-D-aspartate (NMDA). We now know that it works on receptors that also are stimulated by glutamic acid. When the brain becomes stressed, “gaps” can develop between the nerves or neurons. This exacerbates the condition of depression and other disorders. Ketamine stimulates brain derived neurotrophic factors and helps neurons to grow and bridge these gaps. This is proposed to be the mechanism behind ketamine’s dramatic effect . This effect can happen very quickly, sometimes within an hour. In contrast, most anti-depressive meds can take weeks if not months before having any beneficial impact.

Ketamine seems to have truly miraculous effects in the treatment of depression. To date, most of the focus around ketamine for treatment resistant depression has focused on intravenous infusions. However, recent research has demonstrated that other treatment modalities are also effective in treating depression. Researchers examining ketamine nasal spray found that patients showed significant improvement in depressive symptoms at 24 hours after ketamine compared to placebo with 8 of 18 patients (44%) receiving relief receiving ketamine compared with 1 of 18 (4%) receiving placebo. They further concluded that intranasal ketamine was well tolerated with minimal side effects . In my pharmacy, we have also used sublingual ketamine in either a liquid form or troche that dissolves under the patients’ tongues with similar results.

Although the field of using ketamine for the treatment of refractory depression is in its infancy and questions of the safety of long term use of ketamine remain, the clinical, scientific and anecdotal evidence is becoming overwhelming that this drug may provide hope for people suffering from various psychiatric maladies where other treatments have failed. Share this article with your health care provider to start the conversation.

Great interview on WZZM 13
[1]Theodore A. Henderson,  Practical application of the neuroregenerative properties of ketamine: real world treatment experience.   AL REGENERATION RESEARCH
February 2016,Volume 11,Issue 2
[1] A Kyle A.B. Lapidus, Cara F. Levitch, Andrew M. Perez, Jess W. Brallier, Michael K. Parides,Laili Soleimani, Adriana Feder, Dan V. Iosifescu, Dennis S. Charney, and James W. Murrough.   Randomized Controlled Trial of Intranasal Ketamine in Major Depressive Disorder.  Biol Psychol 2014 (
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6 Responses to Ketamine for Treatment Resistant Depression

  1. Great article. Can you please provide the social history and exercise history of the patient? Did the patient get food allergy testing? Did the patient go to South America? Any parasites?

    • Keystone says:

      Dr Singh,
      Dr Dave asked me to arrange a meeting so you can both discuss this case and the general context of Ketamine for off label use. He is always thrilled to consult with prescribers on patients and treatment issues that the pharmacy will be involved with. Let me know what your convenience is. He is willing to come to your practice since we are both so close.
      This would be very involved correspondence if email was used.

  2. You completed a number of nice points there. I did a search on the issue and found nearly all people will have the same opinion with your blog.

  3. Having had treatment resistant depression, had ECT, denied TMS, tried every last psych med in the books, been in Pine Rest and Forest View a total of 10 times, had genetic testing, been to Cleveland Clinic and Mayo Clinic, I am super frustrated that a) insurance will not cover a dime of ketamine infusion therapy for treatment resistant depression (and they covered all of the above for me!) and b) there are zero places anywhere near Grand Rapids offering ketamine infusion therapy even if I could raise the cash (because of course they all only take cash.)
    Only the rich in the big cities get to conquer treatment resistant depression.

    • Keystone says:

      We agree with your challenges. Our pharmacy has been looking for providers to partner with for local treatment and have not yet been successful. is a possible model treatment program and we would be a willing partner!

  4. Joe Scheraldi says:

    We live outside of Orlando Florida (zip code is 34711)
    My wife is suffering from severe depression which was triggered by some medication she took for Hep C.
    Hep C is now cured but now she is suffering with this depression.
    Can anyone provide drs , (in our area) who treat with Ketamine and also any compound phramacies in our area?
    Thank You
    Joe Scheraldi

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