Ketamine Rapidly Relieves Depression by Restoring Brain Connections 10/05/2012 — Nancy Sajben MD

Ketamine Rapidly Relieves Depression by Restoring Brain Connections

10/05/2012 — Nancy Sajben MD

This research is one of the most dramatic findings in the field of depression and mood disorders. It was published in Science by researchers from Yale and the National Institute of Mental Health, discussed by PBS here.

The speed with which ketamine can relieve major depression is deeply moving to witness. In my experience prescribing nasal ketamine it works almost 100% of the time. I have discussed ketamine and previous publications on it for Major Depression and PTSD. It is also effective for suicidal and bipolar depression patients.

Ronald S. Duman, PhD, the lead scientist, reviews his group’s research in this 2011 video:

Stress and depression leads to structural changes in the brain and these structural changes are reversible.

Depression affects 17% of the population, almost one in five of the population. Only one third of patients are effectively treated by existing antidepressants, even after many weeks. Nerve growth factors, in particular BDNF, are decreased by stress, with a very significant loss in depressed patients. BDNF produces antidepressant behavior in rodent models of depression.

BDNF is important for influencing the survival and function of neurons.

There are certain neurogenic zones in the brain that produce new neurons. Stress decreases the number of new neurons. Chronic antidepressant use increases the numbers and proliferation of these new neurons. Antidepressant treatment increases neurogenesis and this is dependent upon BDNF, this neurotrophic factor.

[His slide shows] Exercise, Prozac, ECT, antipsychotics, antidepressants increase neurogenesis.

Not only are there more synapses made by ketamine, but they are a larger size which is indicative of ones that are more functionally connected. Antidepressants take many weeks. A single dose of ketaminerapidly reverses depressive behaviors and loss of connections and completely reverses the decrements that had occurred over several weeks.

In suicidal patients given ketamine at Yale in the Emergency Room, within a matter of hours, the suicidality is completely reversed. These people are better for weeks after a single dose of ketamine treatment. [emphasis mine]

Therapeutically ketamine is even more rapidly acting than ECT.

Ketamine increases BDNF. But research shows its effects are blocked in mice that are deficient in BDNF. Riluzole also influences BDNF, but the side effect profile is so serious that I would not consider prescribing it without more data on safety.

Safety concerns are often raised in publications regarding chronic ketamine use. Most of my patients have no side effects at all. It is one of the safest medications we have and only a small percentage experience transient side effects. The favorable side effect profile, simplicity and low cost is key. The results for nasal ketamine are not 100%, neither is IV ketamine, but I have patients who respond to nasal spray when they failed IV ketamine. More importantly, they can carry it in their pocket and use as needed.

My experience prescribing ketamine goes back almost to the year 2000 for persons with chronic pain who have used ketamine several times daily, and since Spring 2012 for Major Depression. Its effect for depression lasts longer than for chronic intractable pain where it is short lasting. In the past, I prescribed it orally, by mouth, but since late 2011 I have prescribed it in a nasal spray and that form works for depression.

The neuroprotective action of ketamine has been published since at least 1988.

Patients can use nasal ketamine as needed. Schedules vary, everyone is different. It is short acting, but it does not stop working.

However, the use of other adjuvants, such as glial modulators, in treatment of depression is essential to understand, and is now work in progress. The role of inflammation and glia in the pathogenesis of depression has been well established since 2000, and discussedhere.

Does ketamine also restore brain connections in patients with chronic pain? Chronic pain and major depression both lead to brain atrophy and memory loss. Both cause the same imbalance in glial cytokines. Both may respond to glial modulators, e.g. low dose naltrexone among others that have worked in some patients.

“The original link between ketamine and relief of depression was made at the Connecticut Mental Health Center in New Haven by John Krystal, chair of the department of psychiatry at Yale, and Dennis Charney, now dean of Mt. Sinai School of Medicine, who helped launch clinical trials of ketamine while at the National Institute of Mental Health,” reported by Yale  here.

I hope to add new approaches to treatment of anxiety that has failed to respond to other interventions.

Original Article-


4 thoughts on “Ketamine Rapidly Relieves Depression by Restoring Brain Connections 10/05/2012 — Nancy Sajben MD

  1. Hello, I have had RSD/CRPS for 6+ yrs now. I was bedridden for the first 4 years from it. After countless injections, surgeries/procedures, different medication combinations etc., I finally had a pain pump implanted. This allowed me to get a minimal sort of living my life back. I could’ve stayed on Social Security Disability (SSD) for the rest of my life, but I was miserable feeling like I had no purpose in the world. I decided n was lucky enough to be able to go back to work, which was huge in helping my depression n mental health. It’s been 13+ months (started September 14th, 2011) since I’ve been working full-time again. I am finding that it is getting harder n harder to get through each day. It is both a physical n mental fight every second of every day n then I have to wake up n do the same thing the next day.
    When I first had the pump implant n was still out on SSD, it worked well n kept my pain to a minimum, but I was off my feet most of the time. Now that I’m forced to be on my feet more each day, my pain is once again out of control! I’m so used to dealing with extraordinary amounts of pain these days that each work day I’m able to put a smile on my face n try my best to act like all is well because I KNOW that no one understands what I’m dealing with, which in turn, makes me feel like I’m all alone in my own little world. My life becomes more n more miserable with each passing day. So much so that the most comforting thought that I have these days is knowing that I can choose to end my life at any point if I choose to do so if I decide I cannot tolerate this awful pain anymore. Not that I’m actually planning to do so, but the mere thought gives me comfort knowing that at least I have some sort of control over this terrible illness ultimately. It. Has only been 13+ months n I already feel like I cannot continue to work n push myself the way I am anymore. I seriously don’t think there is a high possibility for me to sustain this much longer n little to no chance to sustain it long term. The decision is a catch 22. I’m not sure what’s worse; working n being miserable from the high pain levels, or not working n being miserable feeling like I have no purpose in the world again. Though I’m starting to think that not working will give me a better quality of life, however, I do not want to give up my fight n let the RSD beat me!
    Anyway, I have been researching n looking into Ketamine as an option to help with both my pain n the severe depression I deal with daily. I saw in this post (above) that Yale University Medical Center’s ER uses Ketamine. I was wondering if I would be able to set up an appointment with a Doctor at Yale to learn about the possibility of getting proper treatment. If u are able, could u please get back to me with a few Dr’s names n contact info so I can go about seeking Ketamine treatment at Yale University or elsewhere if u know of other treatment centers. I live in Northern NJ, but am willing to travel to ANY state in America to get the help I so desperately need. I would be eternally grateful n extremely appreciative. Thank you in advance for ANY direction, advise or info you are able to provide.
    Best Regards,
    Robert Alfieri
    Cell #- 862.686.1097


  2. Dear Dr Sajben,
    I suffer from chronic treatment resistant depression that hasn’t responded to many medications. I live in London, UK. Would you be able to prescribe the nasal spray to me? And if not do you know of anyone prescribing it in the UK….Very best wishes…I finally have some hope that Ketamine could help me. Thank you.


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