Ketamine for Antidepressant-Resistant PTSD

Jan 23, 2017

Although hundreds of thousands of active duty military personnel and veterans suffer from posttraumatic stress disorder, there are only two U.S. Food and Drug Administration-approved medications for treating PTSD. Both of those medications are a type of drug called monoaminergic antidepressants. Unfortunately, approximately 45 percent of PTSD patients do not improve from treatment with antidepressants. Many of those who do respond to antidepressants only show a partial improvement and continue to suffer from significant PTSD symptoms.

Mounting evidence indicates that the anesthetic ketamine produces a rapid and potent improvement in up to 90 percent of patients with severe antidepressant-resistant depression. Pilot evidence and case reports also indicate that ketamine may be effective for treating PTSD, but it has not been tested in active duty military personnel or veterans.

To further understanding of this potential treatment, principal investigator John Krystal, MD, of Yale University School of Medicine has developed a study for the Consortium to Alleviate PTSD. Dr. Krystal and his team of investigators will examine the safety and effectiveness of ketamine in active duty military personnel and veterans with antidepressant-resistant PTSD.

The study also will evaluate:

  • Whether treatment benefits may be extended safely through repeated dosing,
  • Whether different dosage levels affect treatment, and
  • How long the benefit of treatment lasts for those who respond to ketamine treatment.

Dr. Krystal and his research team seek to determine in this multi-site, double-blind clinical trial whether ketamine produces a rapid and sustained reduction in PTSD and depression symptoms, as compared to placebo.

Investigators will conduct the study at the Clinical Neurosciences Division of the U.S. Department of Veterans Affairs’ National Center for PTSD at the VA Medical Center in West Haven, Conn.; at the Minneapolis VA Health Care System; and at the U.S. Army’s San Antonio Military Medical Center. They will randomly place nearly 200 study participants into one of three treatment conditions, consisting of either one of two dosage levels of ketamine administered intravenously or a placebo. After the dosage period ends, investigators will follow up with the study participants for four weeks. All study participants who do not experience significant clinical improvement in PTSD symptoms at the end of the 4-week trial will be given the option of receiving a single dose of ketamine.

The number of participants makes this the largest known clinical trial of ketamine in any population.

Expected benefits

Because many PTSD sufferers do not respond to treatment with antidepressants, other treatment options are needed. If successful, this study will provide valuable data on the potential of ketamine to help antidepressant-resistant PTSD patients.

Investigators also believe that it is the first test of the therapeutic effects of ketamine in the veteran and active duty military population, as well as the first placebo-controlled, multi-site trial to determine the dose-related effects of repeated ketamine on PTSD. That will yield valuable information on the efficacy of a drug that could bring relief to help active duty personnel to resume their military careers, and to help veterans transition to civilian lives without PTSD.