A clinical trial found that six intravenous doses of ketamine spread over 2 weeks significantly reduced the symptoms of post-traumatic stress disorder (PTSD). The effect lasted for about 4 weeks after the final dose.

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Some people who have gone through a shocking, frightening, or dangerous experience develop the chronic and distressing symptoms of PTSD.

According to the National Institute of Mental Health, the symptoms of PTSD can include flashbacks, bad dreams, and frightening thoughts.

Individuals with the disorder often avoid places, objects, or events that remind them of their traumatic experience. They may be easily startled or liable to angry outbursts and have trouble sleeping.

The Department of Veterans Affairs report that about 8 million adults in the United States experience PTSD in any given year. They also estimate that approximately 10% of females and 4% of males will develop PTSD at some point during their lifetime.

Treatment for PTSD may involve selective serotonin reuptake inhibitor (SSRI) antidepressants, psychotherapy, or a combination of both. However, these established treatments can take several weeks to start reducing symptoms, and they may not work for everyone.

In a 2014 clinical trial, researchers at the Icahn School of Medicine at Mount Sinai in New York found that a single injection of ketamine led to significant and rapid improvements in PTSD symptoms.

The same team now reports that a series of six intravenous infusions of ketamine in the space of 2 weeks may significantly improve symptoms for about 4 weeks after the final dose.

“PTSD is an extremely debilitating condition, and we are pleased that our discovery may lead to a treatment option for so many who are in need of relief from their suffering,” says Dr. Dennis S. Charney, senior author of the new paper.

The team’s findings appear in The American Journal of Psychiatry.

Ketamine prevents a signaling molecule called glutamate, which stimulates nerves, from binding to a particular receptor in the brain. The Food and Drug Administration (FDA) originally approved the drug for use as an anesthetic in 1970.

Since then, however, researchers have discovered that subanesthetic doses of the drug can rapidly relieve treatment-resistant depression. In 2019, the FDA approved esketamine — a form of ketamine — for treating this type of depression.

In the new study, the researchers randomly assigned 41 people with severe, chronic PTSD (of whom, 35 completed the study) to receive intravenous infusions of either ketamine or a sedative drug called midazolam. The team chose midazolam because it has similar behavioral effects to ketamine and so could act as a control.

The participants had developed PTSD after exposure to various traumatic events, including sexual assault or molestation, physical assault or abuse, witnessing a violent assault or death, surviving or responding to the 9/11 attacks, and military combat.

Overall, they had been experiencing the symptoms of PTSD for a median of 15 years.

The participants self-rated their depression and PTSD symptoms 24 hours after the first infusion and then at weekly intervals. They also underwent assessment by doctors at these stages.

At 2 weeks after the final infusion, those who received ketamine showed significantly greater improvements in the severity of depression and PTSD symptoms compared with those who received midazolam.

In the ketamine group, 67% of the participants responded to treatment (defined as a 30% reduction in PTSD symptoms) compared with 20% of those in the control group.

Among those who responded to ketamine, improvements occurred 24 hours after the first infusion. The median time before the effects wore off was 27.5 days after the final infusion.

Importantly, the authors report that ketamine was well-tolerated overall without any serious adverse events.

Future studies may investigate whether giving additional doses of ketamine or combining repeated infusions with psychotherapy might prolong the benefits further.

Dr. Adriana Feder, associate professor of psychiatry at the Icahn School of Medicine and the lead author of the study, concluded:

“We want people suffering with PTSD to know that hope is on the horizon, and we are working diligently to collect the information that will help bring them the relief they so desperately need.”

The Icahn School of Medicine have filed several patents in the U.S. and around the world that cover the use of ketamine as a treatment for PTSD. The patents name Dr. Charney and Dr. Feder as co-inventors.