Over the next several years, victims of car accidents, crimes, or other traumas who are treated at Boston's Massachusetts General Hospital will be offered a commonly used heart drug–the β-adrenergic blocker propranolol–to potentially help lessen the intensity and future impact of traumatic memories.
Patients who participate in this study will be part of a wave of new drug trials aimed at intervening early to alter memory processes and prevent posttraumatic stress disorder (PTSD). Other studies are planned to aim at intervening later to treat PTSD by effecting memory “reconsolidation,” the process by which memories that have been reactivated are then restored.
As neurobiologists press on with research to better understand the mechanisms and processes involved in acquiring and storing traumatic memories, clinical investigators say they cannot wait to field-test propranolol and other commonly available drugs, some of which appear to target specific mechanisms of action in fear memory.
And some physicians may not even be waiting for study results. According to anecdotal reports, propranolol is already being used off label sporadically in the immediate wake of traumatic experiences.
Possible Clinical Benefits
“There's a real good possibility [we'll soon be using] more specific medications than we have now that will help us deal with the effects of psychological trauma [on the brain],” said Dennis S. Charney, M.D., dean of research at Mount Sinai School of Medicine, New York.
“We'll likely be able to use medication to facilitate fear extinction, to reduce the consolidation of fear memories, and in a rational way, to use medications to augment the effects of psychotherapy,” he said.
The study at Massachusetts General builds on a pilot study, published in 2002, that suggested that posttrauma administration of propranolol in the emergency room may have a “preventive effect” on subsequent PTSD. (See sidebar.)
Harvard/NIMH Study Design
Roger Pitman, M.D., who led the pilot study and has a $2.5 million grant from the National Institutes of Mental Health to conduct the larger double-blind randomized study, hopes to recruit at least 100 patients who have both experienced a traumatic event and present with tachycardia of at least 80 beats/min.
According to Dr. Pitman, most of the published and soon to be published studies addressing the issue of tachycardia as a predictor of PTSD “have been positive.”
Patients in his study will be randomized to receive, within 6 hours of the event, a 10-day course of placebo or propranolol followed by a 9-day taper period, said Dr. Pitman, professor of psychiatry at Harvard Medical School, Boston.
Propranolol is commonly used to treat high blood pressure and for other cardiovascular purposes. It is also prescribed, albeit less frequently, as an antianxiety therapy adjunct for people with public speaking anxieties, fear of flying, and other phobias. It is the only β-blocker that can cross the blood-brain barrier, Dr. Pitman said.
Possible Mechanism of Action
Dr. Pitman latched onto the idea of testing the drug for PTSD prevention 10 years ago, when Larry Cahill, Ph.D., of the Center for the Neurobiology of Learning and Memory at the University of California, Irvine, reported that in a small study of healthy people, the drug significantly impaired memory of an emotionally arousing story but did not affect memory of an emotionally neutral story (Nature 1994;371:702-4).
The findings backed a long-standing hypothesis that enhanced memory associated with emotional experiences results from activation of the β-adrenergic stress hormone systems, particularly in the amygdala. If β-adrenergic receptors are blocked, the theory goes, the consolidation of emotional memories–the formation and storage of long-term emotional memories–can be toned down. As some neurobiologists like to describe it, “overconsolidation”–and overly strong emotional memories–can be prevented.
“The study bridged the gap,” Dr. Cahill said. “It looked like what we were seeing in animals would hold up in humans.”
Studying SSRIs for PTSD Prevention
Other physicians have their eyes on the use of selective serotonin reuptake inhibitors (SSRIs) for PTSD prevention.
At Massachusetts General, Mark Pollack, M.D., is testing the SSRI Lexapro (escitalopram) “at the next potential point of intervention”–in patients who, within a few weeks after trauma, are experiencing acute stress symptoms but do not meet the full criteria for PTSD.
The possible mechanisms of action of the SSRIs in such cases are not all clear, but the hope is that the drugs will help interrupt the cycle of increased arousal and anxiety that may predispose to full-blown PTSD, said Dr. Pollack, director of the hospital's Anxiety and Traumatic Stress Disorders Program. SSRIs are often used (with moderate success) today to treat syndromal PTSD.