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Intranasal Ketamine Confers Rapid Antidepressant Effect in Major Depressive Disorder

Finding may point to new drug class

Researchers at the Icahn School of Medicine at Mount Sinai have published the first controlled evidence showing that an intranasal ketamine spray conferred an unusually rapid antidepressant effect — within 24 hours — and was well tolerated in patients with treatment-resistant major depressive disorder (MDD).

This is the first study to show benefits with an intranasal formulation of ketamine. Results from the study were published online April 2 in Biological Psychiatry.

Of 18 patients completing 2 treatment days with ketamine or saline, eight met response criteria to ketamine within 24 hours compared with one patient given saline. Ketamine proved to be safe, with minimal dissociative effects or changes in hemodynamic dimensions.

The study randomly assigned 20 patients with MDD to receive ketamine (a single 50-mg dose) or saline in a double-blind, crossover design. The change in depression severity was measured using the Montgomery–Åsberg Depression Rating Scale. Secondary outcomes included the durability of response, changes in self-reports of depression, anxiety, and the proportion of responders.

“One of the primary effects of ketamine in the brain is to block the NMDA [N-methyl-d-aspartate] glutamate receptor,” said principal investigator James W. Murrough, MD. “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.”

One of the most common NMDA receptor antagonists, ketamine is an FDA-approved anesthetic. It has been used in animals and humans for years. Ketamine has also been a drug of abuse and can lead to psychiatric or cognitive problems when misused. In low doses, ketamine has shown promise in providing rapid relief of depression, with tolerable side effects.

The researchers hope to examine the mechanism of action, dose range, and use of functional brain imaging to further elucidate how ketamine works.

Source: Mount Sinai Hospital; April 8, 2014.

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