Propranolol, a beta-blocker that cuts heart rate, could silence the disastrous events on repeat in the minds of millions of people with PTSD.
The boom of the plane hitting the towers, the gray pieces floating in the air, and the people jumping out were parts of the scene replayed in physician Margaret Dessau's mind for years after the 9/11 disaster. She remembers looking out her apartment window to see a "guy with this white towel, and he's waving it." After he jumps, she hears children scream from a nearby school.
Nearly 10 years later, she described these memories as part of her post-traumatic stress disorder, or PTSD, to writer Anemona Hartacollis for the New York Times. Many PTSD sufferers replay disastrous events as memories that intrude on everyday life -- intrusive memories -- or in nightmares. They complain of not sleeping or concentrating. They may overreact to loud noises, become excessively alert and hypervigilant, and avoid reminders of the disaster. Dessau, who witnessed the attacks from her window, avoids looking at the skyline.
Intrusive memories are only part of a larger picture that often includes a sense of isolation, hopelessness, anger, and emotional numbness.
These symptoms have made the news for years, but less is known about effective treatment. If disturbing memories can be calmed by drug-enhanced treatment, millions of people who suffer from PTSD might benefit. This affects millions of adults in the U.S., including 9/11 survivors and combat veterans. Now Dr. Alain Brunet, a clinical psychologist at McGill University in Montreal, and his collaborators are halfway through a clinical trial to see if propranolol, a beta-blocker that reduces heart rate and blood pressure -- and has been proven to calm musicians facing stage fright -- can also reduce the strength of long-standing traumatic memories.
"I hear a woman scream ... there was a woman across the street from us, and we thought she had dynamite and was going to kill us. So I killed her."
They are giving the drug just before having people describe their memories in several sessions. Adrenaline and its cousin noradrenaline, the same chemicals that trigger the fight-or-flight response, enhance the storage of fearful memories. Propranolol may block these actions on a cluster of nerve cells deep inside the brain.
Don't try this at home. Propranolol requires medical supervision to be used safely.
I spoke with Brunet about the state of research on propranolol-enhanced treatment. He and his colleagues administered propranolol 75 minutes before the reactivation of frightening memories in 40 patients. "It really did wonders," he told me. "After six sessions, 70 percent of patients no longer met the clinical criteria for PTSD." His recent study with Dr. Roger Pitman, a Harvard psychiatrist who directs the PTSD and Psychophysiology Laboratory at the Massachusetts General Hospital, and others appeared in the 2011 Journal of Clinical Psychopharmacology. Their patients were victims of trauma such as accidents, rape, and spousal abuse, and most had symptoms for years or decades. Symptom relief compared favorably to generally lengthier treatment with psychotherapy alone as reported in earlier studies.
Their current international study, funded by both Canadian and U.S. agencies, is designed to show whether this treatment works even when patients are randomly assigned to either propranolol or a placebo.
In an earlier placebo-controlled study, Pitman reported in Biological Psychiatry that patients treated with propranolol in the emergency room hours after a physical trauma, like an auto accident, were much less likely to show physical reactions to recalling their experience three months later. Here the treatment appeared to reduce the formation of new memories.
The PTSD burden on combat veterans is huge. One said that every night "I hear a woman scream ... there was a woman across the street from us, and we thought she had dynamite and was going to kill us. So I killed her," he told psychologist Paula J. Caplan for the Washington Post. It turned out that she did have dynamite and was planning to kill them. "But every night," he continued, "I hear her scream, because, well, I wasn't raised to kill."
Given the extent of the problem, there is some satisfaction that we can point to a location for disturbing memories. When medical students study the human brain, they identify a small cluster of nerve cells deep inside, called the amygdala from a Greek word based on its resemblance to an almond. This structure plays a key role in a fear network, storing memories of emotionally-charged experiences. Imagine it as a special memory stick for your computer where you save video clips of frightening events.
The location of the amygdala in the brain can be roughly visualized using your right hand with a forefinger curled around the thumb. The amygdala would be a small object at the tip of your thumb. The forefinger in front of the thumb represents the prefrontal cortex, the most advanced part of the human brain in primate evolution, located just behind the forehead.
The prefrontal cortex normally keeps the amygdala operating normally. But if it loses control, emotional memories and reactions can get out of hand. In fact, Pitman told me by phone, "probably the best-documented findings in PTSD show underactivity in the prefrontal cortex."
Normal emergency reactions lead to a release of adrenaline and noradrenaline, chemicals that help increase heart rate and open tiny bronchioles that bring air into the lung. These reactions can help the body deal with emergencies by enhancing the oxygen supply to the muscles. (Adrenaline is also known as epinephrine, a drug used in the Epi-Pen in treating severe allergic reactions.)
Within the brain, adrenaline and noradrenaline can activate structures on the surface of nerve cells called adrenergic receptors. The type known as beta-adrenergic receptors seem to enhance the amygdala's ability to store memories of frightening events. During evolution, the ability to store memories of dangerous situations and react accordingly could be life-saving.
But as we see in the symptoms of the 9/11 witness and the war veteran, these reactions can become excessive and cause suffering for years after the emergency has passed. Since propranolol blocks beta-adrenergic receptors -- it's a beta blocker -- researchers predicted that it might prevent traumatic memories from solidifying. When emotionally-charged memories are reactivated, they are in a more fluid state, neuroscience models suggested. Propranolol given within a specific time-window can interfere with their ability to solidify again. In more scientific terms, it can block the reconsolidation of threatening memories.
The drug-enhanced behavioral treatment studied by Brunet, Pitman, and their colleagues is not yet widely available outside a research setting. How close is the method to clinical practice? Right now, Pitman said, "physicians are able to prescribe a drug for a new indication if in their judgment it would be helpful.... If we get a positive result, people may be inclined to try it for that purpose. But I personally would like to see a replication before it's used more widely. It would be a great beginning ... a step down a path toward eventual application."
Today, cognitive-behavioral treatment alone, targeted at thoughts and emotional reactions, can provide significant help. Current guidelines for effective PTSD treatment describe controlled exposure to troubling memories in a therapeutic setting to regain cognitive mastery, and strategies to help people correct maladaptive thoughts about the event -- thinking they were guilty for not saving others, for example.
Furthermore, stress-inoculation training teaches methods to reduce anxiety such as calm breathing and muscle relaxation. Symptomatic improvement can be assisted with antidepressant medications such as Prozac and other medications for insomnia.
The witness to 9/11 through her window, the combat veteran, and millions of others who suffer PTSD symptoms would benefit if an effective drug-enhanced treatment were available in addition to these treatments. Propranolol is a major candidate for such a drug, but others are being tried that target different memory mechanisms. We can be cautiously optimistic that greater relief for intrusive memories may be in sight.
Images: 1. Straight 8 Photography/Shutterstock; 2. Robert Lavine, adapted from Dorling Kindersley/Getty.
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