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Why your suicidal patient might benefit from ketamine – the latest evidence

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Over the last month or so, there has been some blogging and podcasting on suicide risk assessment and the topic of suicidality on general. If you have not caught up with this then check it out!
Broomedocs Podcast 3 Suicide with Minh
Broomedocs podcast 10 Suicide assessment with Rob Orman

The US military have of late become more interested in research into rapid antidepressant and antisuicidal therapies due to increased suicides in soldiers in current service.
US army antisuicidal nasal spray

The challenging aspect of managing suicidality in the ED or primary cAre setting, is that we know many will contact us prior to any completed suicide attempt, so there is a window of opportunity to intervene. We know though that our main interventions are very limited and often take a long time to work i.e current antidepressant medications.

We say to ourselves, its not like sepsis management where there are proven interventions that we know that if given early, will improve outcomes rapidly, like IV antibiotics. The Surviving sepsis campaign has been well ingrained in our emergency care thinking!

But what if there was a Surviving Suicide campaign? What if there was an IV therapy that was rapidly effective against suicidal symptoms? What if the earlier you diagnosed and administered this therapy, lives could be saved? What if suicidal state was in fact an inflammatory state of the brain?

Well for those who follow my blog, you would know I have written on the antisuicide properties of ketamine before. This has been recognised increasingly in the last 5 years.

I have noticed this in my prehospital and retrieval experience, with suicidal patients who are agitated, not responding to benzodiazepines, antipsychotic agents like olanzapine, but some IV ketamine seems to resolve the agitation. Of course I assumed this was of the general anaesthetic properties of ketamine, but I noticed it would often take no more than sub anaesthetic doses of ketamine to be effective, 20-40mg IV boluses. It is my conclusion that I have been witnessing now a specific antisuicide quality of ketamine.

Many colleagues are skeptical of this observation as a proposed mechanism for why ketamine should have uniquely antisuicide property has been elusive…

till now..

In an advanced online publication that is open access in the Journal of Neuropsychopharmacology , January 2013, international researchers have measured inflammatory markers in the CSF of patients admitted with suicide attempt and found these interact with NMDA receptors. These inflammatory markers were elevated significantly during the acute suicidal state but declined at 6 month followup. Thats right, they repeated the lumbar puncture at 6 months. They propose that the ketamine rapid antisuicidal effect is due to its NMDA antagonistic effect, opposing the inflammatory stimulation of the NMDA receptors within the Brain.
Its not perfect RCT evidence but it is growing body of evidence that novel pathways of neurobiology in suicidal states may hold promise to developing NMDA active agents, and that a prehospital IV agent like ketamine may one day become the Surviving Suicide campaign early intervention!

Here is the full open access article. Read it!
Connecting inflammation with glutamate agonism in suicidality

7 Comments Post a comment
  1. Minh,
    Do you ever have to give a loading dose of ketamine or go straight to the lower dose boluses? Hope we get to see you at Bond uni ressie!
    Cheers,
    John Roe
    Darwin, NT

    January 17, 2013
    • Hi John! Happy new year and second semester !

      All things being equal if there is significant agitation, I tend to give an adequate IV loading dose as the start of an infusion based protocol. Load and set maintenance rate and observe for five half lives. Thats the retrieval sedation protocol I wrote and use.

      For the suicide research protocols, the most common used is a 0.5-0.75mg/kg IV infusion over 40min, once again, aiming to reach plasma steady state level. No loading or titration in the studies as far as I am aware,

      January 18, 2013
  2. Amy Neilson #

    Minh, this is interesting… and it is not the first I have heard of ketamine as novel management of suicidal patients recently. I am not sure if you are aware but there has been some work on this in a private clinic in Brisbane throughout 2012. Not a trial, but rather some private prescribing that is perhaps hoped to lead to evidence to warrant clinical trials.

    It’s certainly novel, and to that end there must always be caution. But there are also some early potentially promising results – or so I hear.

    What I understand of it is that the use is oral and low dose (0.25-0.75mg/kg) and indeed it is understood/believed that at sedative doses the reduction in suicidality is specifically NOT seen. Wierd, but interesting, and consistent with the doses you are using (though yours are IV, so not a direct comparison).

    Cheap, useful and safe are all good things….

    Clinical trials would be hard to design – certainly among the settings I am aware of in psychiatry. How to placebo control for example?

    Interesting stuff. Thanks for posting the link.
    Cheers,
    Amy

    January 17, 2013
    • thanks Amy for the feedback. I was aware there was a clinical trial in Australia started last year
      http://www.abc.net.au/catalyst/stories/3618352.htm
      but that involved placebo infusion and was administered by an anaesthetist, similar to trial protocols done overseas.

      I came across an article on intranasal outpatient ketamine therapy in teenagers with refractory bipolar illness..once again small case series only and not controlled. But they claim to have obtained FDA approval for a RCT trial
      http://www.childadolescentpsychopharm.com/sample-articles/intranasal-ketamine-examined-for-pediatric-bipolar-disorder

      Oral ketamine has limited bioavailability so not sure of its efficacy in an out patient setting as you describe. The intranasal therapy seems promising with one patient being supposedly well maintained on ketamine via intranasal route for 4 years!

      Lets be clear though. I have never treated depression using ketamine as the primary indicAtion. But I have used it in sedation to manage agitation of those with acute mental health conditions and some of them have been suicidal and depressed. All of them failed to have alleviation of their agitation using firstline agents such as benzodiazepines and antipsychotic agents.

      My point in all this is that the traditional belief and teaching that ketamine is contradindicated in patients with mental health conditions like psychosis, agitated depression etc, is not true. In fact the latest evidence suggests it is beneficial in several mental health conditions!

      January 18, 2013
  3. To the contrary. Ketamine acts on the animal side of the brain the right side and it is soooo muchh more efficient in treating depression because it acts faster i mean minutes to hours than antidepressant which might take weeks… its just hard to admit from fellow doctors or FDA to recognize this unique property of K. i mightself have used it for years on moderate level. because lets not fool each other it does have serious long term effect on ur bladder.
    but if one can control it and get administer IV or IM… you will see depression come down as well as suicadal thoughts.
    Sir you are 100% correct, and i would like to repost this fine article on my blog Fansforcharity.com. thank you

    January 20, 2013
  4. Reblogged this on Fansforcharity.

    January 20, 2013

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