Physicians at the Center for the Study of Traumatic Stress at the Uniformed Health Services University of the Health Sciences in Bethesda, Md., have started a similar study, administering an SSRI to car accident victims days to several weeks after the event. Robert Ursano, M.D., who chairs the department of psychiatry at the university, is optimistic enough about these and other studies that he says that “PTSD may be the first psychiatric illness that we'll be able to prevent.”
Therapeutic Window of Opportunity
A major question faced by investigators concerns the timing of the memory consolidation processes. “We don't know what our window of opportunity is,” Dr. Pitman said. “In the most pessimistic estimate, it takes 30 minutes. And it takes at least 30 minutes for propranolol to be absorbed. Some data suggest, though, that the process may take 8 hours.”
Some physicians think that given these uncertainties–as well as lingering questions about who is most at risk for developing PTSD, and limitations in reaching many people early after trauma–it may be more feasible to intervene later and to work on memories that already have formed.
The idea is to reactivate or retrieve the memory and, while it is briefly vulnerable, attempt to weaken it before the memory is restored.
At the October meeting of the Society of Neuroscience, investigators from the Center for Neural Science at New York University presented preliminary findings from animal and human studies that suggested that propranolol at least partly disrupts the “reconsolidation” of fear memories, via the amygdala, making the memories significantly weaker. One of the studies, led by Jacek Debiec, M.D., of New York University, New York, was published in the October issue of Neuroscience (2004;129:267-72).
Other Research Ventures
NYU physicians have begun working with others at the multi-institutional Center for the Neuroscience of Fear and Anxiety on testing whether propranolol helps PTSD patients who take it after recalling traumatic experiences.
Dr. Pitman also is planning a study with Karim Nader, Ph.D., a neuroscientist at McGill University in Montreal, in which they will invoke traumatic memories of PTSD patients and measure the ability of propranolol to reduce the subsequent strength of the memories.
The notion of “reconsolidation” is still controversial among neuroscientists. It's unclear what exactly happens to memories after they're reawakened, and whether attempts to block reconsolidation processes actually block memory restorage or make memories harder to retrieve.
Ethical questions have been raised, but Dr. Nader maintains that the term “therapeutic forgetting”–a phrase that has helped fuel some of the ethical debate–is misleading.
“Memory erasure isn't what we're aiming for. We know that with reactivation of a memory the mechanisms mediating the intensity of the memory will also undergo reconsolidation, and that's what we're targeting,” he said. “We're trying to affect the intensity of the memory … to turn down the volume.”
Current Clinical Use
In the meantime, it is unclear how many physicians have recommended drugs such as propranolol to try to prevent posttrauma suffering.
Physicians contacted by this newspaper said they're unaware of propranolol being used off label for this purpose. Dr. Pitman, however, said that while he does not condone it, “it's happening … I've heard anecdotal reports.”
“I hope we'll hear more about propranolol, especially with the war, with terrorism,” Dr. Debiec said. “We know the drug, we know it's safe.”
Small Pilot Studies Serve as Backdrop
Dr. Pitman's initial study of propranolol is one of two small pilot studies that have looked at treatment with the drug shortly after a traumatic event.
Forty-one patients were randomized in the emergency department at Massachusetts General Hospital to begin–within 6 hours of a traumatic event–a 10-day course of propranolol (40 mg four times daily) or placebo. Eighteen of the 41 received propranolol.
Patients in the double-blind study were instructed to return 1 and 3 months later for assessment with the Clinician-Administered PTSD Scale (CAPS). At the 3-month follow-up, investigators also measured patients' physiologic responses during script-driven imagery of the traumatic event.
At 1 month, the PTSD rate was 30% in the placebo group (6 of 20 patients who returned for follow-up) and 18% (2 of 11 who returned) in the propranolol group.
At 3 months, the CAPS scores did not differ. However, the psychophysiologic testing results suggested that propranolol had an impact. None of the 8 propranolol patients who participated, but 6 of the 14 participating placebo patients, were physiologic responders, reported Dr. Pitman and his associates (Biol. Psychiatry 2002;51:189-92).
The second study was a nonrandomized study of patients who were treated in the emergency departments of two hospitals in France. Eleven patients received propranolol for 7 days (40 mg three times daily), with the first dose administered 2-20 hours after the trauma and with a taper period of 8-12 days. They were compared with 8 patients who refused propranolol but agreed to participate.