New Findings on Ketamine

Ketamine, a drug approved for use as a general anesthetic and sedative, also appears to provide significant relief to patients with major depressive disorder, and those with chronic post-traumatic stress disorder (PTSD), according to two separate studies conducted by researchers at Icahn School of Medicine at Mount Sinai.

In the first study, which appeared online in the April 2 issue of Biological Psychiatry, Mount Sinai researchers found that using an intranasal ketamine spray worked within 24 hours to relieve depressive symptoms in patients previously considered treatment-resistant. Traditional antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), can take weeks, or even months, to reduce symptoms of depression.

The second study, published online on April 16 in JAMA Psychiatry, showed that an IV infusion of ketamine provided rapid relief to patients with moderate-to-severe post-traumatic stress disorder. The low-dose intranasal spray and IV infusions appeared to be safe and well tolerated by patients in the short term.

“One of the primary effects of ketamine in the brain is to block the activity of the NMDA (N-methyl-D-aspartate) glutamate receptor,” says James W. Murrough, MD, Assistant Professor of Psychiatry and Neuroscience, and Associate Director of the Mood and Anxiety Disorders Program at Icahn School of Medicine, who was the principal investigator of the study on major depression. “There is an urgent need to identify new treatments for depression that have novel mechanisms of action in the brain.” As many as 40 percent of depressed individuals, or 112 million people worldwide, are believed to be resistant to conventional therapies.

Adriana Feder, MD, Associate Professor of Psychiatry at Icahn School of Medicine, and a lead author on the study involving patients with PTSD, says her research “should be viewed as a proof of concept study. Longer-term clinical trials with ketamine will be required to determine if ketamine will be a clinically useful treatment for PTSD.” Mount Sinai’s was the first randomized study to demonstrate the rapid effect of ketamine on patients with PTSD.

“In recent years, we and others have shown that ketamine could often counter the symptoms of depression in treatment-resistant cases,” says Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, and President for Academic Affairs, Mount Sinai Health System. “Now we have shown that ketamine is associated with significantly greater reduction in core PTSD symptom levels 24 hours after a single IV infusion.

We hope to see this line of research developed further.” In 2000, Dr. Charney and John H. Krystal, MD, Chair of the Department of Psychiatry at the Yale School of Medicine, published the first controlled study showing that intravenous infusions of ketamine produced rapid antidepressant effects.

Dr. Dennis Charney and Icahn School of Medicine at Mount Sinai have been named on a use patent on ketamine for the treatment of depression. The Icahn School of Medicine at Mount Sinai has entered into a licensing agreement for the use of ketamine as therapy for treatment-resistant depression. Dr. Charney and Icahn School of Medicine at Mount Sinai could potentially benefit from the results of the study. In addition, Dr. Charney and Dr. Adriana Feder are named co-inventors on a use patent application filed by Mount Sinai for the use of ketamine as a treatment for PTSD. If ketamine were shown to be effective in the treatment of PTSD and received approval from the U.S. Food and Drug Administration (FDA) for this indication, Dr. Charney, Dr. Feder, and the Icahn School of Medicine at Mount Sinai could benefit financially.

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