Special K and Depression

Special K - active ingredient ketamine - is an illegal club drug that was originally used as a medical anesthetic. But now scientists are reporting that it might be a useful ally in the fight against depression:

Researchers at the National Institute of Mental Health announced a study recently in which 18 chronically depressed patients infused with low dosages of ketamine improved within two hours. Seventy-one percent improved within a day, and nearly 30 percent were depression-free by that time. In 24 hours! These were people who had been dealing with depression from three to 47 years. They had failed to respond to just about every drug on the market.

Most of them stayed depression-free for up to a week.

I sure wish the FDA and NIH were more open-minded about using illegal drugs for scientific research. These chemicals clearly give people pleasure, and it's time to find out why. I'm not advocating ecstasy or special-K as an over the counter anti-depressant, but perhaps we can fine-tune these substances so that we get the ecstasy in tolerable doses (and without the awful hangover).

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The newspaper report is based on Zarate et al., "A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression", Arch Gen Psychiatry. 2006;63:856-864. You can see the abstract here.

It's a small study, progress was measured subjectively, and despite the claim in the abstract I find it hard to believe that it was really double blind (surely it would have been obvious to the participants who was on the placebo?). So I think a bit of skepticism is in order.

Ketamine is a Schedule II drug -- the same as most narcotic painkillers.

It is commonly used (still) in ER's for certain types of anesthesia -- mostly for setting simple fractures. Its also used in some cases of uncomfortable exams (kinda as a super Nitrous Oxide). It can be legally (and is occassionaly) used in physician offices for certain procedures.

Using it outside of anesthesia would be new, but I don't see it as a huge issue. I doubt however that physicians will want to write scripts for it.

Thanks for the excellent and informative comments. I've modified the post to reflect Dan's note about the continued use of ketamine, and I urge everyone to take Gdr's skepticism into account. He's right about the danger of lending too much credence to a very small study that only measured results subjectively.

The small size is something to keep in mind, but the criticism of "subjective" verification is a red herring, seeing as we are talking about a malady of (subjective) affect, after all*.

surely it would have been obvious to the participants who was on the placebo?

This is probably a problem with "blinded" studies of any rapid-onset psychotropic substances. As the authors say,

"Several factors need to be considered in interpreting these data. Although the sample size was relatively small, 3 different types of analysis showed the significance of ketamine over placebo, and the effect sizes of this study were very large at day 1 and moderate to large at day 7. Consistent with all of the published randomized, placebo controlled studies with ketamine, we also found shortlived perceptual disturbances; such symptoms could have affected study blind. Hence, limitations in preserving study blind may have biased patient reporting by diminishing placebo effects, thereby potentially confounding results. One potential study design in future studies with ketamine might be to include an active comparator such as intravenous amphetamine (a dopamine agonist), which also produces psychotogenic effects.
However, the time of onset and course of antidepressant response (relatively prolonged) after receiving only 1 dose of ketamine was nearly identical for each subject; this pattern suggests that there was indeed a true drug effect. "

*Below are the 'Outcome Measures':

"Subjects were rated 60 minutes prior to the infusion and at 40, 80, 110, and 230 minutes, as well as 1, 2, 3, and 7 days, after the infusion. Rating scales included the 21-item HDRS, which was the primary outcome measure, and the secondary outcome measures: the Beck Depression Inventory (BDI), Brief Psychiatric Rating Scale (BPRS) positive symptoms subscale, Young Mania Rating Scale (YMRS), and the visual analog scale. Raters (research nurses, a physician, and a psychologist), who trained together to establish reliability, performed patient ratings. High interrater reliability for the HDRS (intraclass correlation coefficient=0.81) and the YMRS (intraclass correlation coefficient=0.91) were obtained. Clinical response was defined as a 50% or greater decrease in the HDRS score from baseline and remission was defined as an HDRS score of 7 or lower."

I doubt anyone familiar with ketamine would be fooled by its replacement with amphetamines.