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March 18, 2004


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HARVARD GAZETTE ARCHIVES

Pill to calm traumatic memories

Puts the mind's storehouse in order

By William J. Cromie
Harvard News Office

Every day, people suffer traumatic experiences that scar their minds. Combat, rape, bombings, burns, beatings, and horrific car accidents haunt them with
Wedig, Pitman, Buhlmann
Psychiatrist Roger Pitman checks a simulated test to detect the effects of post-traumatic stress disorder. Ulrike Buhlmann (right), a research fellow, adjusts electrodes on volunteer Michele Wedig which record rapid heartbeats, sweating, muscle twitches, and other signs of stressful memories. (Staff photo Jon Chase/Harvard News Office)
memories impossible to suppress. Such day- and nightmares are part of a problem known as post-traumatic stress disorder, or PTSD.

Psychotherapy - talking it through with a professional - doesn't always bring the peace PTSD sufferers seek. Roger K. Pitman, professor of psychiatry at Harvard Medical School, believes such people can be helped with new drugs that he and others are testing.

"I feel that, sooner or later, we will find a drug that can prevent or substantially reduce PTSD," Pitman says.

He and his colleagues tested a tongue-twister of a drug called propranolol on 41 people who had experienced automobile accidents, assaults, and other traumas serious enough for them to be treated at the emergency room of Massachusetts General Hospital in Boston. The goal was to see if this drug, given within six hours of their mishaps, would prevent terrifying, indelible memories.

Tested three months after an auto accident, one young man, who took a dummy pill as part of the experiment, was still wary about getting into a car. He had nightmares. He sweated, his heart rate jumped, and he felt nervous anytime he got behind the wheel, especially in the area where the accident occurred.

In contrast, others who survived similar accidents and took propranolol had significantly fewer problems.

The most revealing tests were done three months after the traumas, when 22 of the victims returned to Mass General Hospital for evaluation. Eight of these people took propranolol four times a day for 10 days, but had been off the drug for more than two months when tested. Fourteen of the 22 had taken dummy pills, or placebos.

All of them listened to audiotapes on which they had described the incidents that brought them to the emergency room. None of those who took propranolol showed strong responses to the tapes. But eight of the placebo patients were obviously shaken by reliving their traumas. Their heart rates increased, their palms sweated, their muscles twitched - all signs of PTSD.

Living with bad memories

That's a pretty good result. It hints that giving propranolol to soldiers traumatized by combat in Iraq and Afghanistan, to young boys or girls who have been sexually assaulted, to victims of terrorist bombings and rape might be a good idea. But Pitman is a cautious scientist. Before issuing propranolol or any other PTSD drug to military medics, firefighters, police officers, and emergency medical technicians, more testing needs to be done with larger numbers of people.

Why did some of the people who didn't take the drug come out as well as those who did take it? What's the best dosage? What about side effects? To get answers, Pitman and his colleagues have begun a study that will include about 200 people who are treated for trauma in the emergency rooms at Massachusetts General and Brigham and Women's hospitals in Boston. Both hospitals are affiliated with Harvard Medical School.

Pitman's colleagues are testing another drug, paroxetine (Paxil), on burn victims. Paxil has already been approved for treatment of PTSD but not for its prevention. Propranolol is approved for treating hypertension.

Recently, investigators in France reported on experiments showing that propranolol reduces PTSD symptoms. Researchers at the University of California, San Diego, have also been testing propranolol and another drug called guanfacine. They are expected to publish their results soon.

"The object of these drugs is not to make people forget their traumatic experiences," Pitman explains, "but to reduce the intensity of the memories to a more normal level, a level that a person can easily live with."

He sees post-traumatic stress disorder as a perfectly natural process gone amok. Pitman puts it this way: Suppose one of our primitive ancestors, while looking for a good water hole in Africa, is attacked by a crocodile. That person had better remember where the attack took place or he or she stands to be removed from the human gene pool.

Activation of stress hormones like adrenaline in such situations stirs an animal or person to flight or fight. It also sharpens their memory. But, Pitman says, such a response sometimes "can be too much of a good thing. A process I call 'superconditioning' leads to the formation of a deeply engraved traumatic memory that subsequently manifests itself as the intrusive recollections and emotional responses of post-traumatic stress disorder."

Along with deliverance from death and disaster, you get a disorder. Propranolol shows a potential for curing that disease.

A widespread mental illness

According to a national study, about 8 percent of the U.S. population, some 20 million people, get PTSD sometime in their lives. It is the most important mental illness dogging the military. During the Vietnam War, about one of every three people involved in combat developed post-traumatic stress disorder. A surprising number of nurses who treated those soldiers, sailors, and Marines suffered from it, too. Pitman expects the same number of those who experience combat and terrorism in Iraq and Afghanistan to be PTSD casualties.

Giving propranolol to combatants in the field is not an idea that pleases generals, Pitman points out. Its anti-adrenal effect could block the will to fight along with easing heart palpitations and nightmares. But it could be given to those who are being evacuated, if medics have a good idea of who is most likely to suffer the disorder. Pitman's colleague, Scott Orr of Harvard Medical School, is doing experiments with firefighters and police officers to try to identify individuals who are most likely to be traumatized after experiencing intense stress.

That type of know-how would be helpful for people charged with the emergency care of civilians. In such cases, there is the additional problem of obtaining informed consent to administer drugs. Then there's the question of what is the best time to give such drugs. "There must be a critical window of time when PTSD drugs would be most effective," Pitman notes. "In the study at Mass General we gave propranolol within four hours of the trauma, maybe one hour would be better."

Finally, there's the ethical question. Leon Kass, chairman of the President's Council on Bioethics, objects to propranolol's use on the grounds that it medicates away one's conscience. "It's the morning-after pill for just about anything that produces regret, remorse, pain, or guilt," he says.

Pitman, however, thinks that an effective PTSD drug would do a lot more good than harm.







Copyright 2007 by the President and Fellows of Harvard College