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Ketamine: New Potential as Rapid PTSD Treatment Not Just for Depression Anymore?

Caroline Cassels April 17, 2014


The first evidence from a randomized clinical trial that the anesthetic agent ketamine may provide rapid symptom reduction in patients with chronic posttraumatic stress disorder (PTSD) when delivered intravenously has been published. An N-methyl-D-asparate (NMDA) glutamate receptor, ketamine has made headlines in recent years because several trials conducted by investigators at the Icahn School of Medicine at Mount Sinai in New York City have shown that it delivers a rapid antidepressant effect when delivered intravenously and, most recently, intranasally in spray form. In this latest proof-of-concept study, researchers led by Adriana Feder, MD, found that intravenous (IV) infusion of ketamine hydrochloride (0.5 mg/kg) was associated with significant and rapid reduction of PTSD symptom severity compared with an active control agent. "These findings may lead to novel approaches in the treatment of chronic PTSD ― a condition that affects a broad spectrum of adults in the United States and beyond, including victims of sexual assault, war veterans, those who have witnessed catastrophic events such as the September 11 terror attacks, and others," Dr. Feder, associate professor of psychiatry, Icahn School of Medicine at Mount Sinai, said in a release. "However, this should be viewed as a proof-of-concept study. Additionally, longer-term clinical trials with ketamine will be required to determine if it will be a clinically useful treatment for PTSD," she added. The study was published online April 16 in JAMA Psychiatry. Fast-Acting Antidepressant Few pharmacotherapies have demonstrated sufficient efficacy in the treatment of PTSD, which is chronic and disabling, the investigators note. They add that there is a growing body of evidence showing that glutamate plays a major role in mediating stress response, the formation of traumatic memories, and PTSD pathophysiology. An agent that has been used for anesthesia at 2 mg/kg and analgesia at subanesthetic doses, ketamine has a good safety track record and is superior to other anesthetic agents because it reliably preserves breathing reflexes. The researchers note there have been no randomized clinical trials examining the effect of ketamine in chronic PTSD. The few that have been conducted were either retrospective or nonrandomized. Building on previous research showing that ketamine is effective in treatment-resistant depression, the investigators conducted a proof-of-concept, randomized, double-blind, crossover trial comparing ketamine with an active placebo control, midazolam, another anesthetic agent that has pharmacokinetic parameters and nonspecific behavioral effects that are similar to ketamine. "In recent years, we and others have shown that ketamine could often counter the symptoms of depression in treatment-resistant cases. In the present study, we hypothesized that ketamine would be associated with significantly greater reduction in core PTSD symptom levels 24 hours after a single IV infusion, and that it would also improve comorbid depressive symptoms in patients diagnosed with PTSD," principal investigator Dennis Charney, MD, Anne and Joel Ehrenkranz Dean, Icahn School of Medicine at Mount Sinai, sa