Intended for healthcare professionals

Rapid response to:

Clinical Review

Post-traumatic stress disorder

BMJ 2015; 351 doi: https://doi.org/10.1136/bmj.h6161 (Published 26 November 2015) Cite this as: BMJ 2015;351:h6161

Rapid Response:

Re: Post-traumatic stress disorder

I appreciate that a CPD article intended for general medical readers has to be brief, as evidence based as possible, and highlight the main points. Readers wishing to broaden their interest in Post Traumatic Stress Disorder (PTSD) may wish to be aware of the possible emerging role of Ketamine in treating PTSD and indeed may wish to be aware that there is an animal study which suggests that Ketamine may have a prophylactic role in preventing the condition from occuring.

Whilst many caveats apply to observational studies, in one observational study investigating the prevalence of PTSD in Operation Iraqi Freedom/Operation Enduring Freedom service members who were treated for burns in a military treatment center it was found that among 119 patients who received ketamine during surgery and 28 who did not the prevalence of PTSD was 27% (32 of 119) versus 46% (13 of 28), respectively - almost a 20% reduction (1).

In a randomized, double-blind, crossover trial comparing ketamine with an active placebo control, midazolam, conducted at a single site involving forty-one patients with chronic PTSD intravenous infusion of ketamine hydrochloride (0.5 mg/kg) was associated with significant and rapid reduction in PTSD symptom severity, compared with midazolam, when assessed 24 hours after infusion (mean difference in Impact of Event Scale–Revised score, 12.7 [95% CI, 2.5-22.8]; P = .02). Greater reduction of PTSD symptoms following treatment with ketamine was evident in both crossover and first-period analyses, and remained significant after adjusting for baseline and 24-hour depressive symptom severity. Ketamine was also associated with reduction in comorbid depressive symptoms and with improvement in overall clinical presentation. Ketamine was generally well tolerated without clinically significant persistent dissociative symptoms.The authors concluded that their study provided the first evidence for rapid reduction in symptom severity following ketamine infusion in patients with chronic PTSD, which if replicated might lead to novel approaches to the pharmacologic treatment of patients with this disabling condition(2).

The role of Ketamine in enhancing stress resilience was tested using a chronic social defeat (SD) stress model, learned helplessness (LH) model and a chronic corticosterone (CORT) model in mice. Mice were administered a single dose of saline or ketamine and then 1 week later were subjected to 2 weeks of SD, LH training, or 3 weeks of CORT. Mice treated with prophylactic ketamine were protected against the deleterious effects of SD in the forced swim test and in the dominant interaction test. The effects were confirmed in the LH and the CORT model. In the LH model, latency to escape was increased following training, and this effect was prevented by ketamine. In the CORT model, a single dose of ketamine blocked stress-induced behavior in the forced swim test, novelty suppressed feeding paradigm, and the sucrose splash test. These authors concluded that ketamine can induce persistent stress resilience and, therefore, may be useful in protecting against stress-induced disorders (3). Furthermore, according to the authors "If this research translates to humans,ketamine could be used as a prophylactic against stress-induced psychiatric disorders, a use of pharmacotherapy not even considered previously” (4).

As one enthusiastic advocate has termed it: Ketamine : the new penicillin of psychiatry (5) and whilst not directly related to PTSD, another has stated that “The rapid therapeutic response of ketamine in treatment-resistant patients is the biggest breakthrough in depression research in a half century”(6)

1. McGhee et al,The Correlation Between Ketamine and Posttraumatic Stress
Disorder in Burned Service Members The Journal of TRAUMA Injury, Infection, and Critical Care 2008;64:S195–S199

2. Feder et al, Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress DisorderA Randomized Clinical Trial JAMA Psychiatry. 2014;71(6):681-688. doi:10.1001/jamapsychiatry.2014.62

3. Brachman RA et al, Ketamine as a Prophylactic Against Stress-Induced Depressive-Like Behavior Biol Psychiatry. 2015 May 4. pii: S0006-3223(15)00360-1. doi: 10.1016/j.biopsych.2015.04.022

4. http://newsroom.cumc.columbia.edu/blog/2015/07/02/could-a-dose-of-ketami... last accessed 26 11 15

5. http://prehospitalmed.com/2015/09/19/ketamine-the-new-penicillin-of-psyc... last accessed 26 11 15

6. http://news.yale.edu/2012/10/04/yale-scientists-explain-how-ketamine-van... last accessed 26 11 15

Competing interests: Over the years I have attended meetings and had lunches/dinners sponsored by a range of pharmaceutical firms and equipment manufacturers. My work on Ketamine is frequently referenced in the book "Ketamine for Depression" written by Dr Stephen J Hyde which is where I first came across accounts of the use of Ketamine in PTSD.

26 November 2015
Varun K Jaitly
Consultant Anaesthetist with an interest in Pain Medicine
Wrightington Wigan and Leigh NHS Foundation Trust
Department of Anaesthesia, Royal Albert Edward Infirmary, Wigan Lane, Wigan WN1 1NN