Ketamine and Depression

January 01, 2006  ·  Michael Fumento  ·  American Spectator  ·  Disease

After reading Michael Fumento’s article several points need to be made. In the first place, after clicking the link and reading the study itself, it bears emphasizing that the sample size-18 patients, is extremely small. This by definition makes it difficult to say much with certainty about the validity of the outcomes the authors are trying to measure. In addition, since all of these people failed 6 conventional antidepressants, making them an unusual subset of patients, one can say nothing at all about whether this treatment would be superior to, inferior to, or even work on the vast majority of patients who DO respond to conventional antidepressants. Secondly, Ketamine is far from a benign drug. There are several reasons why it is used primarily in veterinary practice, and only sparingly, if at all, by most anesthesiologists (including myself) in this country. It significantly raises blood pressure and cardiac oxygen demand, making it an increased risk for, if not outright inappropriate to use for those with heart disease. It also causes unpleasant, and often extremely unpleasant, visual, auditory, or proprioceptive hallucinations in the immediate post dose period and subsequent nightmares in as many as 30% of patients. The resource Mr. Fumento cites somewhat glosses over this difficulty, claiming that the delirium and dreams go away in 24 hours, however, this need not be the case, and there is much anecdotal evidence which indicates that harrowing nightmares may persist for weeks or even months after a single dose. Thirdly, one of the circumscribed areas of anesthetic practice where Ketamine is popular is in severe burn cases, which often have to be seen to surgically multiple times over a period of weeks. Anyone who has done this notes that a marked tolerance develops, requiring continuously increased doses to achieve the same therapeutic effects. While there is nothing in the study to suggest this would be the case in treating depression, since the patients did not receive long term treatment, there is nothing to rule it out. The test subjects received half of the dose required to induce the low end of general anesthesia, meaning there is not a lot of wiggle room to increase the dose if tolerance is indeed an issue. Having said all of that, it IS an interesting avenue for further research. However, the tone of the piece suggests that a possible cure for depression is just around the corner. This somewhat akin to saying "Hey, some guys just figured out how to make a wheel out of wood, lets start building an interstate system."

B.J.M. M.D.

Michael Fumento responds:

Dr. B.J.M. appears to be looking for an argument, a la the fellow in the Monty Python skit who keeps looking for the argument room but just ends up getting contradiction and abuse. For example, he says he had to click on the link I provided to see how many people were in the study (as if it were a major revelation) when I said so in the body of the article. He also ignores my mention of a previous small study with similar results. There are also animal studies which had similar results and therefore led to the human ones.

I suggested that if ketamine be used in its present injectable form, it only be used for extreme cases. To this B.J.M says the study at hand is of limited value because all the participants were extreme cases. Huh? It also obviates his argument about whether the results would apply to non-extreme cases although I can’t imagine why it would only work on the brains of people who are resistant to traditional therapy.

When it comes to side effects, Dr. B.J.M. is talking about the much-higher doses used in anesthesia. Normally smaller doses lead to fewer and lesser side effects. Certainly in the aforementioned trials the effects he describes were not found. I don’t think ”glossed over ” is fair. Nor is it fair for him to rely on "anecdotal evidence." Where’s the science?

Finally, I hardly implied a cure for depression is right around the corner for two reasons. First, the aforementioned trials were promising treatments but just that; a treatment is not a cure. Second, it would take at least five years to bring such drugs to the market unless by happy coincidence a company happens to have something sitting on the shelf that’s already undergone safety testing for something else, as indeed is the case with injected ketamine. What should be around the corner is what I said: ”What we need is for the pharmaceutical industry to take this tantalizing research and run with it. ” It will be too late for my brother-in-law but sadly there are many more like him that with current medicines will follow his fatal path.