Veterans sought for PTSD treatment study

September 08, 2017 12:00 am • Last Updated: September 09, 2017 10:08 pm

A new study will examine whether ketamine is a safe and effective treatment for post-traumatic stress disorder, and researchers are looking for veterans in Connecticut to participate.

Commonly prescribed for anesthesia, ketamine is known both as a party drug and a proven and fast treatment for depression. At Yale-New Haven Hospital and a number of other hospitals around the country, ketamine is used to treat depression in patients who haven't responded to typical antidepressant medications and psychotherapy, said Yale University professor John Krystal, the lead researcher for the PTSD study.

Krystal is one of the discovers of the antidepressant effect of ketamine, and a patent that he and other researchers developed for ketamine for depression was licensed by Johnson & Johnson.

Now, early signs show ketamine has unique benefits for treating chronic PTSD. If proven effective, the drug likely would not be used as a so-called frontline treatment such as antidepressants and psychotherapies, but rather for patients who don't respond to those traditional treatment methods.

"PTSD is the most common and the most costly psychiatric disorder for the Department of Veterans Affairs to treat," and yet there very few treatment options, Krystal said. The treatment of chronic PTSD is particularly a challenge, he added.

The study will take place at two main sites: the Department of Veterans Affairs Medical Center in West Haven, which is primarily recruiting veterans to participate, and the Brooke Army Medical Center in San Antonio, Texas, which is recruiting active-duty military personnel. Researchers are looking for more than 100 participants.

This will be one of the first studies to test ketamine as a treatment for PTSD, and the first study of ketamine to include active-duty military personnel, according to Krystal.

Being exposed to chronic stress for a long period of time can result in the loss of semantic connections in the brain — the brain's connections of words, perceptions and actions. Ketamine has shown, through animal research studies and use in the treatment of depression, to rapidly regrow these semantic connections.

"When these semantic connections regrow and the circuits are functioning better, then mood regulation can return to a more normal pattern, and response to psychotherapy gets better and adjustment in life gets better, and basically that overall recovery takes place as long as, in the case of depression, you repeat the ketamine periodically to maintain richness of semantic connections," Krystal said.

Participants will come in twice a week for four weeks to get the treatment. The expectation is that most participants already will have tried antidepressants, and many of them still will be on those antidepressants when they enter the study, Krystal said. Participants randomly will be assigned to one of the three doses: the typical ketamine antidepressant dose, a little less than half the typical ketamine antidepressant dose, or saline.

"We're trying to figure out not only does it work but what’s the right dose," Krystal said.

The study also will include four weeks of follow-up to determine how long the benefits last.

Compared to antidepressants, which are often taken daily, the expectation is that ketamine could be taken more infrequently. When used safely and in clinical practice, "Generally you start receiving it twice a week then you move to once a week. Almost all patients can get to every other week treatments and about 40 percent are maintained with one treatment every month or even less frequently," Krystal said, referring to ketamine's use in treating depression.

Generally, ketamine is safe but there is concern that its immediate benefits may encourage recreational use. The drug can make people hallucinate, among other side effects.

The study has big implications. The VA estimates that 30 percent of Vietnam vets have PTSD, and that the rate for Gulf War vets is 12 percent, and between 11 and 20 percent for post-9/11 vets.

On top of that, research has shown that vets with PTSD are more at risk for suicide. Ketamine has effectively reduced suicidal ideations in depressed patients, according to Krystal.

"The fact that it works so quickly, in other words most people tend to respond to ketamine within 24 hours as opposed to a month or two, then that's particularly important for people who are at risk for self harm," he said.

Ketamine has also proven to be good for physical pain as well as psychological pain in the context of PTSD, Krystal said, noting that there might be an opportunity in the future to study how to jointly manage the physical and the psychological pain, "which could be another important application of ketamine for PTSD."

j.bergman@theday.com