Just 24 hours after receiving intranasal ketamine, patients with treatment-resistant major depressive disorder showed significant improvement in symptoms with minimal adverse effects, according to researchers from the Icahn School of Medicine at Mount Sinai, New York City.
Their findings, which provide the first controlled evidence to document the rapid antidepressant effects of intranasal ketamine, were published in the online Biological Psychiatry.
"One of the primary effects of ketamine in the brain is to block the NMDA [N-methyl-d-aspartate] glutamate receptor," said lead researcher James W. Murrough, MD, Assistant Professor of Psychiatry and Neuroscience and Associate Director of the Mood and Anxiety Disorders Program.
"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."
The randomized, double-blind, crossover study involved 18 patients with major depression who underwent two treatment days with a 50-mg dose of intranasal ketamine hydrochloride or a saline solution placebo.
When researchers administered the Montgomery-Asberg Depression Rating Scale 24 hours following ketamine or placebo administration, they found significant improvement in depression symptoms of eight patients after intranasal ketamine. Only one patient showed significant improvement following placebo.
In addition, intranasal ketamine was well-tolerated in participants, causing minimal dissociative effects or changes in hemodynamic dimensions, researchers reported.
“If replicated,” the researchers concluded, “these findings may lead to novel approaches to the pharmacologic treatment of patients with major depression.”
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