Ketamine (street name Special K) has been used in a variety of ways legal and illegal, in both animals and humans. Its primary use is general anesthesia and sedation of animals. As a recreational drug it is known for its hallucinogenic properties, although it never attained the popularity of other street drugs like LSD, cocaine or ecstasy.
Now, based on studies conducted in 2007 by Dennis S. Charney, MD Mount Sinai Hospital, in collaboration with John H. Krystal, MD, of Yale University, ketamine is being investigated by a number of groups as a new type of antidepressant one with a novel mode of action that sets it apart from the currently most prescribed class of such drugs known as the selective-serotonin reuptake inhibitors (SSRIs).
SSRIs (e.g. Prozac, Lexapro, others) are effective for many patients, but they have significant drawbacks lack of efficacy in many patients, and significant side effects, including sexual dysfunction, nausea, weight gain and insomnia. Perhaps more importantly, they can take a month or more to work, and most patients need to try more than one drug to find what works best for them. Thus, it is not uncommon for depressed patients to suffer for months from the awful condition. And some patients fail to respond to any SSRIs.
But a newly reported study led by Dan Iosifescu, MD and James Murrough, MD at Mount Sinai Hospital, and Sanjay Mathew, MD, at Baylor College of Medicine gives real hope to depression sufferers. Seventy-two patients with refractory depression (failed to achieve relief from at least two different antidepressants) showed some remarkable responses to a single ketamine treatment.
Subjects received a one-dose infusion of ketamine, and were interviewed 24 hours later. This group experienced an astonishing 64% response rate after one day, and this effect lasted for at least one week in 46% of those patients. The group receiving a placebo reported response rates of 28 and 18 percent respectively typical numbers for placebo controls in psychiatric pharmaceutical studies.
ACSH s Dr. Josh Bloom says, Ketamine works by a completely different mechanism from modern antidepressants. Instead of targeting the serotonin pathway, it works via interaction with the glutamine pathway in the brain, which is responsible for the release of multiple neurotransmitters. He continues, If these results hold up in larger trials, Drs. Charney and Krystal ought to be checking airfares to Stockholm. This could be one of the most important medical discoveries in many years.
ACSH s Dr. Gilbert Ross noted the enthusiasm generated by this study, and agreed that refractory depression is a terrible disease indeed. However, rather than writing their Nobel Prize speeches quite yet, I d like to see a much, much larger prospective controlled trial with monitoring of the effects, and possible side-effects, after months of observation. I d term this study a preliminary or pilot study, and look forward to more data which will hopefully confirm the initial excitement.
ACSH friend, Dr. Derek Lowe has a nice discussion in his In the Pipeline blog about ketamine and other drugs that work by similar mechanisms, and their potential as antidepressants. You can read his analysis here.