Response to MJA Editorial on ketamine for depression

Ketamine1

Hi, I contacted Dr Varun Jaitly (@varunja) , UK anaesthetist and pain medicine specialist, to invite comment on Professor Loo’s MJA editorial on ketamine for depression. He kindly provided this detailed response.

Comment: A shortened version of this letter was submitted to the MJA .

As an outside observer – I am anaesthetist with an interest in chronic pain who lives on the other side of the planet – the only thing that qualifies me to make some sort of comment on Loo’ s editorial (1) is the fact that I have some clinical experience in dealing with patients who have been taking regular low dose Ketamine for a long time to manage their chronic pain problems.Several years ago I was encouraged to publish my observations and readers can access the fruits of this labour in the open access article I wrote, where I describe my more than 200 patient years of experience with this drug (2).

Readers with the stamina to read the whole paper can then judge for themselve the risks of whether regular low dose sublingual Ketamine is likely to cause significant hepatic
impairment, bladder dysfunction and cognitive impairment. Alternatively they can accept my summary statement that in my series the patient who had been taking it for the longest time has been taking it for 15 years – and generally speaking in my small group of patients, there was no easily observable harm. Compared to the daily doses of abuse described in the literature which can amount to more than several grammes per day(3), most of my patients are prescribed doses well below this – often of the order of 90-120 mg per day. Furthermore, in my series, no patient reported an easily observable abstinence syndrome when they stopped their Ketamine, even if they discontinued their Ketamine after several years of treatment.

It has been difficult to demonstrate the value of Ketamine in patients with chronic pain and Moore et al’s article ” Expect analgesic failure; pursue analgesic success” goes a
long way to explaining the underlying reasons for this (4). Indeed one of the first ever published n-of-1 studies was that of oral Ketamine in chronic pain , and even that study (5) concluded that oral ketamine only gave rise to an extra analgesic response in three out of 21 patients with chronic neuropathic pain (14%). It is a matter of regret that since then, there has not been an explosion of studies in chronic pain to determine the true value of Ketamine in chronic pain.

Whilst clinical equipoise exists, and if the funding can be provided,  a window of opportunity now exists for psychiatrists to investigate the value of Ketamine using best research practice – the roles that can be investigated include its value as an acute antidepressant which acts as bridging therapy until the classical antidepressants start to work, or as an alternative for those who have treatment resistant depression, or in those
difficult to manage agitated patients who don’t settle with classical interventions.

Clearly randomised studies which can explore practical ways of extending the benefit of the drug are needed. For those doctors already convinced of the benefit of Ketamine, perhaps it may be an idea to ask them to participate in some sort of compulsory online National Register scheme which would cease when the RCT data finally became available. This might at least allow some bench marking,clinical oversight and review by clinical
peers as to what good practice should be. Patients who are commencing Ketamine in this latter scenario should be made aware of the limitations of the data.It goes without saying that practitioners should seek to adhere to advice offered by their professional organisations as well as comply with the legislation requirements of the jurisdiction where they practice.

1.Colleen Loo, Med J Aust 2015; 203 (11): 425

2. Jaitly V.K. Sublingual Ketamine in chronic pain : Service evaluation by examining over 200 patient years of data Journal of Observational Pain Medicine – Volume 1, Number 2 (2013) ISSN 2047-0800 (open access)
http://www.joopm.com/index.php?journal=joopm&page=article&op=view&path[]=26(last accessed 15 12 15)

3. http://www.bbc.co.uk/news/resourcesidt-bc7d54e7-88f6-4026-9faa-2a36d3359bb0

4. Moore et al Expect analgesic failure; pursue analgesic success BMJ 2013;346:f2690
http://www.bmj.com/content/346/bmj.f2690 (last accessed 15 12 15)
5. Haines DR, Gaines SP.N of 1 randomised controlled trials of oral ketamine in patients with chronic pain.Pain. 1999 Nov;83(2):283-7.

I as the writer of this letter retain intellectual property right on the content of this letter. This is an open-access letter distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution,and reproduction in any medium, provided the original work is properly cited.

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