While the study involved a small number of subjects, its results are encouraging, says its senior author, Charles Marmar, MD, associate chief of staff for mental health at the San Francisco VA Medical Center and professor and vice chair of psychiatry at University of California, San Francisco.
"The study is based on the new theory that PTSD is most likely to occur in patients who experience a particularly severe and prolonged response to trauma. If this model proves accurate after five or ten replications of studies like this one, it could have very profound ramifications. From a public health perspective, if you could identify the subgroup of people who are susceptible to PTSD, giving them this course of medication -- which is brief, very well tolerated and inexpensive -- could be very effective prevention [following major trauma] and may have great social relevance." The study appears in the November 1 issue of Biological Psychiatry.
All people confronted by a life-threatening situation, such as a car accident or physical assault, react by releasing a rush of stress hormones, including adrenalin and noradrenalin, which are produced in the adrenal glands, located atop the kidneys. This response, known as "adrenergic activation," initiates the reactions that quicken the heart rate, constrict the vasculature to prevent bleeding to death, and provide energy to the muscles, priming the body to "fight, flee, or freeze." The hormonal flood also strengthens the brain's ability to form and retain emotional memories. The longer the duration of the adrenergic activation, the more vivid and tenacious are the memories of the event. In most people, after minutes to hours the reaction begins to subside.
In some 25 percent of people, however, the hormonal response continues for hours, days, or even a week or longer. The working hypothesis of the new model is that these are the people who are at greatest risk for developing post-traumatic stress disorder, in which a person experiences recurring emotional attacks, for months, years or decades following the inciting event. PTSD patients experience such symptoms as insomnia, difficulty concentrating, persistent reliving of the traumatic event, and reactions of panic or fear when confronted with reminders of the event.
A diagnosis of PTSD is usually made when such symptoms persist at least four weeks following the trauma. For those who suffer from PTSD, memories can be so dogged and intense that they can be triggered years later by details of scenery, smells or sounds associated with the trauma. Some Vietnam veterans with PTSD, for example, feel more anxious on hot and humid days, because these conditions evoke their memories of jungle warfare.
The model now being explored by both basic and clinical researchers predicts that the more quickly a person calms down and regains a sense of safety and composure following trauma, the less vividly the event will be etched in memory, making him or her less likely to develop phobias of objects or actions related to the trauma, and such potent reminders of the trauma will be less likely to trigger panic and fear responses. Recent research involving accident victims in Australia and people exposed to the World Trade Center attacks support this hypothesis.
"Our working model is that if you experience a more intense panic reaction in a life-threatening situation and it takes you a longer period of time to calm down afterwards than most people, you are having a sustained adrenergic reaction and you are more likely to be among those 25 percent of people who are at risk of developing PTSD," Marmar says.
Thus, two important steps in early prevention of PTSD may be to identify the 25 percent of trauma victims who are at greatest risk of developing the disorder and to calm them as quickly as possible in order to block their adrenergic activity.
In the study, doctors in the emergency departments of two hospitals in France evaluated victims of physical assault or auto accidents for symptoms of prolonged panic reactions within two to twenty hours of the traumatic injury. Because one reliable indication of a sustained panic reaction is tachycardia, or elevated heart rate, the doctors chose patients for the study who were medically stable and had heart rates higher than 90 beats per minute measured after they had been lying down for 20 minutes. These patients were offered propranolol, a common drug also known by its brand name, Inderal, which is often prescribed for tachycardia, high blood pressure or anxiety. Those who accepted the drug were given an immediate dose of 40 mg and were then asked to take three daily doses of 40 mg for seven days, followed by a tapering off period of eight to twelve days.
When evaluated with a battery of psychological tests two months following the traumatic event, almost all patients exhibited some degree of symptoms associated with PTSD, but severity of symptoms was twice as high among patients who had not taken propranolol. Only one of 11 propranolol patients had symptoms severe enough to warrant a diagnosis of PTSD, while three of eight patients who declined the drug were diagnosed with the disorder.
Propranolol is one of a class of drugs known as beta-adrenergic antagonists that can control many of the physical symptoms of panic attacks, such as trembling, sweating, tachycardia and heart palpitations. The drug has also been shown to reduce memory for emotional events by blocking adrenergic pathways. For example, when either propranolol or a placebo were given to college students before they were shown disturbing films, the propranolol decreased the students' anxiety both while they watched the film and weeks later when descriptions of the film were read to them.
Treatments for PTSD that have been shown to be beneficial are antidepressant medications and cognitive behavioral therapy -- a form of psychotherapy that works on changing a person's patterns of thinking in order to curb unwanted thoughts and feelings. But the longer PTSD persists, the more difficult it is to treat. Without the benefit of skilled intervention, about a third of those people who have PTSD for a year or longer will suffer from it for many years or even decades. Moreover, many people do not recognize symptoms of the disorder, so they delay seeking treatments. Others are reluctant to ask for treatment for what may be perceived as an emotional disorder, and, in many places, specialized treatment resources are scarce. Given such problems in treating PTSD, many researchers are now looking for ways to prevent or reduce occurrence of the disorder.
Although not a randomized study, the propranolol and control groups did not differ significantly in characteristics such as age (all subjects were 21 to 30 years old), gender, employment, and marital status, degree of exposure, physical injury, or level of terror at the time of the assault or accident. All were medically screened, were free of cardiovascular complications from their exposure, and otherwise in good physical health. No one was enrolled in the study who had lost consciousness during the trauma, sustained serious brain injuries, had injuries compromising cardiovascular function, or who had a history of heart disease, asthma or PTSD.
This is the second study in which propranolol was promptly administered following traumatic injury. The first was conducted by Roger Pitman and colleagues at Harvard and published in 2002. In that investigation, 31 trauma victims who were evaluated in the first hours after traumatic exposure were randomly assigned to take propranolol or a placebo. Pitman's team did not find fewer cases of PTSD in the propranalol group, but propranolol patients experienced lower measures of stress (lower heart rates and skin conductance measurements) than the placebo group when they listened to a vivid narrative of their traumatic event three months after its occurrence.
The first author of the study is Guillaume Vaiva, MD, PhD, at the Clinical School of Psychiatry, University of Lille Medical School, Lille, France. Co-authors are Drs. François Ducrocq, Karine Jezequel, Benoit Averland and Philippe Lestavel, all at University of Lille, and Dr. Alain Brunet, Department of Psychiatry, McGill University and the Douglas Hospital Research Center in Montreal, Canada.
The research was supported by funds from the French Institute of Health and Medical Research.