'Special K' once again wows investigators in small depression study

Yet another research team has pulled off a small study demonstrating the enormous potential of ketamine as a treatment for depression, highlighting again how difficult it has been to push beyond evidence of a rapid-acting treatment to develop a therapy with durable effects.

Mount Sinai Hospital

Ketamine is a generic anesthetic that has taken on a second life as the party drug "Special K," which is associated with some dangerous side effects. Investigators at the Icahn School of Medicine at Mount Sinai say that they developed a low-dose, intranasal formulation of the drug that spurred a clear response among a small group of patients suffering from treatment responsive major depression disorder. Of the 20 patients treated with either intranasal ketamine or saline, "8 met response criteria to ketamine within 24 hours versus one on saline."

That's the third study in just the last three weeks to demonstrate that ketamine, which is known to block the NMDA glutamate receptor, can often produce a sharp, very quick improvement in seriously depressed patients. Just days ago a study at the Oxford Health NHS Foundation Trust demonstrated that out of 28 severely depressed patients treated with low doses of ketamine, 8 showed an improvement and four improved so much they were no longer classified as depressed. The report was heralded by a wide array of mainstream media groups. And just days before that, investigators at Baylor College of Medicine, which has been a center of ketamine research, showed that a low dose of ketamine could quickly resolve suicidal thoughts in depressed patients.

That kind of evidence has caused some people suffering from depression to seek out the drug, even though there has been no proof that it can produce any kind of lasting effect without the danger of side effects. Ketamine's promise in the field has never managed to get beyond these early, small and extremely brief studies, which have been grabbing headlines for years. One of the problems has been that like any party drug, its effect is extraordinary but also of short duration.

Johnson & Johnson ($JNJ) has advanced an intranasal version of the drug, called esketamine, into Phase II. The pharma giant has proclaimed this project as one of their top experimental drugs. And clinicaltrials.gov reveals that a Phase II that started last fall is due to read out in a year. AstraZeneca ($AZN) had a version of ketamine--AZD6765--in Phase II but quickly and quietly killed the project recently after it failed the second of two mid-stage studies. At the time, AstraZeneca offered no detailed explanation of the data or what went wrong with the program.

"One of the primary effects of ketamine in the brain is to block the NMDA [N-methyl-d-aspartate] glutamate receptor," said James W. Murrough, the principal investigator of the latest study at Mount Sinai. "There is an urgent clinical need for new treatments for depression with novel mechanisms of action. With further research and development, this could lay the groundwork for using NMDA-targeted treatments for major depressive disorder."

- here's the release