Study: Ketamine holds promise for PTSD treatment

A fast acting anesthetic approved more than 40 years ago for American soldiers during the Vietnam War may hold the key to better treatment for posttraumatic stress disorder (PTSD) in the 21st century.

Ketamine has already shown effectiveness in lifting symptoms of deep depression. Researchers at the Yale School of Medicine, the VA Connecticut Healthcare System, Mount Sinai School of Medicine and other research institutions are pursuing more studies to learn more about how ketamine can work within hours to alleviate symptoms

“I don’t think any drug is a miracle drug, but I think that ketamine has produced some very exciting data,” says John H. Krystal, M.D., chair of Yale’s department of psychiatry and chief of psychiatry at Yale-New Haven Hospital.

A Yale pilot study found subjects with severe depression given a low dose of ketamine showed a reduction of symptoms within four hours and were, Krystal says, “by the next morning, basically in remission.”

Compare that to SSRI antidepressants like Paxil, which can take four to six weeks before improvement is evident.

Krystal began working with ketamine in 1989 to study schizophrenia. It was first developed for veterinary medicine before being adopted for battlefield surgery because it does not suppress breathing unlike other anesthetics. Ketamine blocks the n-methyl-D-aspartic acid (NMDA) receptor on the glutamate pathway in the brain involved in memory and mood regulation. Researchers think ketamine’s antidepressant effect comes from restoring synapse connections that may have deteriorated under stress and depression.

Other studies have shown similar results, including a 2006 study by the National Institute of Mental Health in which 70 percent of participants experienced rapid symptom relief with one intravenous dose of ketamine.

A 2008 U.S. Army Institute of Surgical Research study found that Operation Iraqi Freedom/Operation Enduring Freedom service members in treatment for burns who received ketamine during surgery had a lower prevalence of PTSD (27 percent) than those who did not (46 percent). The results occurred despite having larger burns, more serious injuries, more surgeries and spending more time in the ICU.

Mount Sinai School of Medicine is currently conducting a study to investigate the effectiveness of ketamine in PTSD patients led by the school’s dean, Dennis S. Charney, M.D., formerly of Yale and a mentor to Krystal. Charney, through a school spokesman, declined to discuss the study while still underway. He indicated he would be able grant an interview sometime in the fall.

Ketamine is sold as a generic under the brand name Ketalar. Large doses can be dangerously debilitating and produce hallucinations. As a popular nightclub street drug, ketamine is known as Special K. It is listed as a Schedule III drug under the U.S. Controlled Substances Act.

Krystal says ketamine has been studied in such a small population so far and ultimately thinks scientists will learn how it works to develop another, safer antidepressant.

“I think it’s been an interesting and useful tool to identify novel ways to treat depression,” he says.