Optimism about New Treatments: Acting Quickly, in the “Golden Hours”

Optimism about New Treatments: Acting Quickly, in the “Golden Hours”

Posted: August 15, 2014

From The Quarterly, Summer 2014

It’s called “the golden hour:” the first hour after a severe trauma when medical intervention has the greatest chance of saving a victim. Dr. Kerry Ressler, who spent some of his medical training in emergency rooms (ER) and still devotes time to seeing trauma patients, says evidence suggests there is a similar golden period after a trauma during which PTSD can be minimized or even prevented.

This window of intervention is probably a number of hours, although research is still determining how much longer it may be, by which time the trauma memories are formed after a traumatic experience. Whenever possible, clinicians need to act quickly. But doing so for every person reporting a trauma would be logistically daunting, not to mention impossibly costly. This is why Dr. Ressler is determined to identify risk genes, so that in the future, a simple blood test can identify the trauma victim in the ER whose genetic profile makes the chance of PTSD more likely.

While the search for risk genes goes forward, doctors know that it pays to treat trauma victims with a behavioral method called “exposure” therapy. The most effective kind has been tested in clinics with both civilians and veterans, where trauma victims receive a course of psychotherapy that includes virtual reality. By virtually recreating the scene of the trauma in a safe, non-threatening environment, doctors often succeed in desensitizing the victim to cues that set off PTSD symptoms.

Earlier this year, Dr. Ressler and colleagues published results of a double-blind study combining virtual reality exposure therapy with a promising medication called D-cycloserine, or DCS. Designed as an antibiotic, DCS selectively stimulates NMDA receptors* in the brain. The medication is thought to help victims extinguish unwanted trauma memories. Dr. Ressler’s trial showed no advantage post-treatment for soldiers who received virtual exposure therapy combined with DCS vs. placebo. But it showed that those getting DCS had lower levels of cortisol, the stress hormone, during therapy, as well as better scores in the “startle-response” test. This paradigm-shifting work suggests that the medication DCS may improve the effectiveness of exposure therapy by enhancing the biological processes that lead to memory extinction. Although more tests will follow, DCS remains a strong candidate for combination treatment.

Another possible treatment-enhancing medication involves the nerve growth factor BDNF (brain-derived neurotrophic factor). In the fear center of the brain called the amygdala, memories cannot be extinguished without BDNF. This suggests BDNF or a medication that acts just like it might be given to people who are undergoing exposure therapy. In the “golden hours,” a BDNF-blocker also might be given to prevent the formation of a traumatic memory. “I think PTSD is going to be tractable,” Dr. Ressler says. “I expect medications similar to BDNF or DCS will be given in a targeted way, and infrequently, to coincide with the time of memory formation or specific subsequent attempts to extinguish traumatic memories.

More generally, everyone in the field agrees this is a time when discoveries are happening quickly. I’m quite optimistic they will lead to better ways of taking care of people with PTSD and even, in some cases, preventing it altogether.”

Friday, August 15, 2014

From The Quarterly, Summer 2014

It’s called “the golden hour:” the first hour after a severe trauma when medical intervention has the greatest chance of saving a victim. Dr. Kerry Ressler, who spent some of his medical training in emergency rooms (ER) and still devotes time to seeing trauma patients, says evidence suggests there is a similar golden period after a trauma during which PTSD can be minimized or even prevented.

This window of intervention is probably a number of hours, although research is still determining how much longer it may be, by which time the trauma memories are formed after a traumatic experience. Whenever possible, clinicians need to act quickly. But doing so for every person reporting a trauma would be logistically daunting, not to mention impossibly costly. This is why Dr. Ressler is determined to identify risk genes, so that in the future, a simple blood test can identify the trauma victim in the ER whose genetic profile makes the chance of PTSD more likely.

While the search for risk genes goes forward, doctors know that it pays to treat trauma victims with a behavioral method called “exposure” therapy. The most effective kind has been tested in clinics with both civilians and veterans, where trauma victims receive a course of psychotherapy that includes virtual reality. By virtually recreating the scene of the trauma in a safe, non-threatening environment, doctors often succeed in desensitizing the victim to cues that set off PTSD symptoms.

Earlier this year, Dr. Ressler and colleagues published results of a double-blind study combining virtual reality exposure therapy with a promising medication called D-cycloserine, or DCS. Designed as an antibiotic, DCS selectively stimulates NMDA receptors* in the brain. The medication is thought to help victims extinguish unwanted trauma memories. Dr. Ressler’s trial showed no advantage post-treatment for soldiers who received virtual exposure therapy combined with DCS vs. placebo. But it showed that those getting DCS had lower levels of cortisol, the stress hormone, during therapy, as well as better scores in the “startle-response” test. This paradigm-shifting work suggests that the medication DCS may improve the effectiveness of exposure therapy by enhancing the biological processes that lead to memory extinction. Although more tests will follow, DCS remains a strong candidate for combination treatment.

Another possible treatment-enhancing medication involves the nerve growth factor BDNF (brain-derived neurotrophic factor). In the fear center of the brain called the amygdala, memories cannot be extinguished without BDNF. This suggests BDNF or a medication that acts just like it might be given to people who are undergoing exposure therapy. In the “golden hours,” a BDNF-blocker also might be given to prevent the formation of a traumatic memory. “I think PTSD is going to be tractable,” Dr. Ressler says. “I expect medications similar to BDNF or DCS will be given in a targeted way, and infrequently, to coincide with the time of memory formation or specific subsequent attempts to extinguish traumatic memories.

More generally, everyone in the field agrees this is a time when discoveries are happening quickly. I’m quite optimistic they will lead to better ways of taking care of people with PTSD and even, in some cases, preventing it altogether.”