Upon request, in the interest of wider circulation, I am putting up as a new thread, slightly modified version of a posting I put up a day or two ago in the ketamine infusions? thread. This is one article that merits all of our attention.
On September 22, 2009, PAIN, the most important journal in the field, anywhere in the world, electronically published a forthcoming article: Outpatient intravenous ketamine for the treatment of complex regional pain syndrome: A double-blind placebo controlled study, Schwartzman RJ, Alexander GM, Grothusen JR, Paylor T, Reichenberger E, Perreault M,
Pain 2009 Sep 22. [Epub ahead of print] a full free text copy of which is now available on the RSDSA Medical Article Achieve page at
http://www.rsds.org/2/library/articl...n_Pain2009.pdf The abstract follows:
Complex regional pain syndrome (CRPS) is a severe chronic pain condition that most often develops following trauma. The pathophysiology of CRPS is not known but both clinical and experimental evidence demonstrate the important of the NMDA receptor and glial activation in its induction and maintenance. Ketamine is the most potent clinically available safe NMDA antagonist that has a well established role in the treatment of acute and chronic pain. This randomized double-blind placebo controlled trial was designed to evaluate the effectiveness of intravenous ketamine in the treatment of CRPS. Before treatment, after informed consent was obtained, each subject was randomized into a ketamine or a placebo infusion group. Study subjects were evaluated for at least 2 weeks prior to treatment and for 3months following treatment. All subjects were infused intravenously with normal saline with or without ketamine for 4h (25ml/h) daily for 10days. The maximum ketamine infusion rate was 0.35mg/kg/h, not to exceed 25mg/h over a 4h period. Subjects in both the ketamine and placebo groups were administered clonidine and versed. This study showed that intravenous ketamine administered in an outpatient setting resulted in statistically significant (p<0.05) reductions in many pain parameters. It also showed that subjects in our placebo group demonstrated no treatment effect in any parameter. The results of this study warrant a larger randomized placebo controlled trial using higher doses of ketamine and a longer follow-up period.
PMID: 19783371 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/1...ubmed_RVDocSum
While it's a small study, finishing up with only 19 participants, its importance cannot be overstated. First, by giving Clonidine and Versed (Midazolam) to all participants, whether they were receiving ketamine or in the control group, were, in the words of the conclusion, "positive placebos" that effected "blinding" on the part of all participants. This it becomes, unbelievably, the first double blinded placebo controlled study of intravenous ketamine in the treatment of CRPS. Granted, one of acknowledged the limitations of the study was its small size, but the robust nature of the results may be enough to secure NIH grants for larger studies. Studies from which WC carriers will hopefully find no escape.
Most surprisingly, the results of the study were obtained from a population of CRPS patients who had been ill for at least six months, and some much longer:
There were no significant differences between those patients with a shorter duration of CRPS (11 patients with an average length of illness of 2.6 years and a range of 0.8–4.2 years) and longstanding patients (8 patients with an average length of illness of 12.2 years and a range of 6.8–20 years).
Although perhaps at the behest of the reviewers, this result is qualified in the conclusion, it should be noted how this is seemingly at variance with a small study undertaken by his German colleagues on which Dr. Schwartzman was listed as the senior author, and in particular the lengthy discussion section at the end of the article. Kiefer RT, Rohr P, Ploppa A, et al, A Pilot Open-Label Study of the Efficacy of Subanesthetic Isometric S(+)-Ketamine in Refractory CRPS Patients,
Pain Med. 2008;9(1):44-54 (among 4 female patients with mean duration of CRPS of 58 ± 20 months, subanesthetic S(+)- ketamine showed no reduction of pain and effected no change in thermo- and mechanical detection or pain thresholds), full text at
http://www.rsds.org/2/library/articl...ohr_Ploppa.pdf
My only disappointment in the new article is that the study design carried over an exclusion criteria for glaucoma from the coma treatments, which made sense in that context where one's eyes apparently "bug out" during the coma, and the doctors feel that they have no means for controlling eye pressures during that time, but it's hard to see how the same rationale applies to sub-anesthetic out-patient infusions. (An issue that caught my attention where I had already purchased - on the last day anything other than full-fare coach prices were available - non-refundable tickets to Germany, before being definitively advised that the exclusion applied even to well controlled "open angle" glaucoma.) But that's just my vantage point. As set forth in the article, there are some other contraindications as well.
The new article is wonderful and the study design is tight. It looks as though all of Dr. Schwartzman's years of toil in the ketamine vineyards may be on the verge of bearing fruit in the manner in which CRPS patients can be treated across North America.
Mike