Ketamine has the potential to prevent post-traumatic stress disorder (PTSD), according to a new study conducted in mice from Columbia University Medical Center (CUMC).
Researchers found that a single dose of ketamine given to a mouse one week prior to a stressful event helped lower its fear response.
The results suggest that ketamine, which is typically used as a general anesthetic or as a fast-acting antidepressant, could be taken prophylactically by those most at-risk for developing PTSD.
"Ketamine is a powerful drug, and we wouldn't advocate widespread use for preventing or reducing PTSD symptoms," said Christine A. Denny, an assistant professor of clinical neurobiology in psychiatry at CUMC who led the study. "But if our results in mice translate to humans, giving a single dose of ketamine in a vaccine-like fashion could have great benefit for people who are highly likely to experience significant stressors, such as members of the military or aid workers going into conflict zones."
But Col. Carl Castro, director of the University of Southern California's Center for Innovation and Research on Veterans and Military Families, and a 33 year U.S. military veteran, is not so confident that the drug is capable of forestalling PTSD symptoms in humans.
"The problem with the entire theory behind [this study] is the assumption that PTSD is due to a fear response, but fear is only a tiny, tiny element of PTSD," Castro told Seeker. "It's a cognitive issue, it's a contextual issue, it's a social support issue, it's a moral issue - none of which these animal models even come close to capturing."
He stressed that one of the problems with using ketamine prophylactically, especially in a military setting, is that you have no way of knowing who will develop PTSD.
"Not everyone gets PTSD following a traumatic event," Castro noted. "Are you going to give a drug to everyone even though most do not develop PTSD? Especially ketamine, which is highly addictive?"
During the CUMC trials, researchers had difficulty knowing how far in advance to administer the ketamine dosage before the mice were exposed to a traumatic event. There were groups that received a single dose of ketamine either one month, one week, or one hour before they were put through a series of small shocks.
Only the mice who had been given the ketamine one week in advance did not exhibit freezing behavior (their typical fear response) when experiencing the shocks, but it's unclear whether there's a window of time between one week and one hour that would be more effective.
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The other issue that Castro sees with a fear-based trial like the CUMC study is that fear is only one component of PTSD's many symptoms. People with PTSD can experience flashbacks to the traumatizing event, hyperreactivity, hyperarousal, and rapid mood changes, as well as physical ailments like headaches. The disorder occurs in about a quarter of people who experience psychological trauma, but the likelihood that it will develop depends on the severity of their experience and how they respond.
"PTSD is a multidimensional disorder, so there's not going to be a single drug that gets at every symptom," Castro said. "Even if ketamine could stop the fear response, what about all the other things that happen? Are you gonna give somebody like 20 drugs? This study takes a very simplistic animal model and then tries to extrapolate it to a very complex human condition. It just doesn't work that way."
The practice of administering pharmaceuticals in the military is not common, but it's not unheard of either.
During WWII, some soldiers were given amphetamine tablets to stave off fatigue and be more alert during battle. As recently as 2003, during the U.S. war in Afghanistan, it was revealed that two Air National Guard pilots were given amphetamines (referred to as "go pills") before they mistakenly bombed Canadian troops. They claimed that the pills had impaired their judgement.
"Pilots are the only group that are allowed to [take amphetamines] by policy," Castro said.
Though he maintains that ketamine is not a solution for PTSD prevention, Castro does believe it could be used as a treatment for other conditions.
"There has been research done with ketamine as an antidote following exposure to nerve agents," he said. "It is highly effective - the data is amazing with ketamine and nerve agent toxicity."
Castro also suggests that ketamine might be effective in reducing phobia, but clarifies that this is different from PTSD.
"What they could use this model for is maybe phobia research, but PTSD is not phobia and people make that mistake as well," he said. "Many people do not deeply understand the mental health disorder that we're talking about."
The CUMC team hopes to begin human trials in the future, but Castro urges that there are other ways of preventing and treating PTSD.
"The most known preventative measure for PTSD is good supportive leadership, which tells you the importance of the social support around you," he said.
Ultimately, there's unlikely to ever be a one-size-fits-all solution to PTSD.
"Some people believe trauma is all the same and has the same underlying biological effect - not true," Castro said. "You're not going to find a single drug that will be effective. It's theoretically and clinically not a relevant idea."
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