January 2005 • www.eclinicalpsychiatrynews.com Neuropsychiatric Medicine 67 Propranolol, Other Drugs Eyed to Block PTSD Idea is that blocking ͱ-adrenergic receptors might Therapeutic Window of Opportunity Dr. Pitman also is planning a study with A major question faced by investigators Karim Nader, Ph.D., a neuroscientist at tone down consolidation of emotional memories. concerns the timing of the memory con- McGill University in Montreal, in which solidation processes. “We don’t know they will invoke traumatic memories of BY CHRISTINE KILGORE Pitman, professor of psychiatry at Harvard what our window of opportunity is,” Dr. PTSD patients and measure the ability of Contributing Writer Medical School, Boston. Pitman said. “In the most pessimistic esti- propranolol to reduce the subsequent Propranolol is commonly used to treat mate, it takes 30 minutes. And it takes at strength of the memories. ver the next several years, victims high blood pressure and for other cardio- least 30 minutes for propranolol to be ab- The notion of “reconsolidation” is still of car accidents, crimes, or other vascular purposes. It is also prescribed, al- sorbed. Some data suggest, though, that controversial among neuroscientists. It’s Otraumas who are treated at beit less frequently, as an antianxiety ther- the process may take 8 hours.” unclear what exactly happens to memories Boston’s Massachusetts General Hospital apy adjunct for people with public speaking Some physicians think that given these after they’re reawakened, and whether at- will be offered a commonly used heart anxieties, fear of flying, and other phobias. uncertainties—as well as lingering ques- tempts to block reconsolidation processes drug—the β-adrenergic blocker propra- It is the only β-blocker that can cross the tions about who is most at risk for devel- actually block memory restorage or make nolol—to potentially help lessen the in- blood-brain barrier, Dr. Pitman said. oping PTSD, and limitations in reaching memories harder to retrieve. tensity and future impact of traumatic many people early after trauma—it may Ethical questions have been raised, but memories. Possible Mechanism of Action be more feasible to intervene later and to Dr. Nader maintains that the term “ther- Patients who participate in this study will Dr. Pitman latched onto the idea of test- work on memories that already have apeutic forgetting”—a phrase that has be part of a wave of new drug trials aimed ing the drug for PTSD prevention 10 years formed. helped fuel some of the ethical debate— at intervening early to alter memory ago, when Larry Cahill, Ph.D., of the The idea is to reactivate or retrieve the is misleading. processes and prevent posttraumatic stress Center for the Neurobiology of Learning memory and, while it is briefly vulnerable, “Memory erasure isn’t what we’re aim- disorder (PTSD). Other studies are planned and Memory at the University of Califor- attempt to weaken it before the memory ing for. We know that with reactivation of to aim at intervening later to treat PTSD nia, Irvine, reported that in a small study is restored. a memory the mechanisms mediating the by effecting memory “reconsolidation,” of healthy people, the drug significantly At the October meeting of the Society intensity of the memory will also under- the process by which memories that have impaired memory of an emotionally of Neuroscience, investigators from the go reconsolidation, and that’s what we’re been reactivated are then restored. arousing story but did not affect memory Center for Neural Science at New York targeting,” he said. “We’re trying to affect As neurobiologists press on with re- of an emotionally neutral story (Nature University presented preliminary findings the intensity of the memory ... to turn search to better understand the mecha- 1994;371:702-4). from animal and human studies that sug- down the volume.” nisms and processes involved in acquiring The findings backed a long-standing hy- gested that propranolol at least partly dis- and storing traumatic memories, clinical pothesis that enhanced memory associat- rupts the “reconsolidation” of fear mem- Current Clinical Use investigators say they cannot wait to field- ed with emotional experiences results ories, via the amygdala, making the In the meantime, it is unclear how many test propranolol and other commonly from activation of the β-adrenergic stress memories significantly weaker. One of physicians have recommended drugs such available drugs, some of which appear to hormone systems, particularly in the the studies, led by Jacek Debiec, M.D., of as propranolol to try to prevent posttrau- target specific mechanisms of action in amygdala. If β-adrenergic receptors are New York University, New York, was pub- ma suffering. fear memory. blocked, the theory goes, the consolida- lished in the October issue of Neuro- Physicians contacted by this newspaper And some physicians may not even be tion of emotional memories—the forma- science (2004;129:267-72). said they’re unaware of propranolol being waiting for study results. According to tion and storage of long-term emotional used off label for this purpose. Dr. Pitman, anecdotal reports, propranolol is already memories—can be toned down. As some Other Research Ventures however, said that while he does not con- being used off label sporadically in the im- neurobiologists like to describe it, “over- NYU physicians have begun working with done it, “it’s happening ...I’ve heard anec- mediate wake of traumatic experiences. consolidation”—and overly strong emo- others at the multi-institutional Center dotal reports.” tional memories—can be prevented. for the Neuroscience of Fear and Anxiety “I hope we’ll hear more about propra- Possible Clinical Benefits “The study bridged the gap,” Dr. Cahill on testing whether propranolol helps nolol, especially with the war, with ter- “There’s a real good possibility [we’ll soon said. “It looked like what we were seeing PTSD patients who take it after recalling rorism,” Dr. Debiec said. “We know the be using] more specific medications than in animals would hold up in humans.” traumatic experiences. drug, we know it’s safe.” ■ we have now that will help us deal with the effects of psychological trauma [on the Studying SSRIs for PTSD Prevention brain],” said Dennis S. Charney, M.D., Other physicians have their eyes on the use Small Pilot Studies Serve as Backdrop dean of research at Mount Sinai School of of selective serotonin reuptake inhibitors Medicine, New York. (SSRIs) for PTSD prevention. r. Pitman’s initial study of propra- propranolol patients who participated, “We’ll likely be able to use medication to At Massachusetts General, Mark Pol- Dnolol is one of two small pilot but 6 of the 14 participating placebo facilitate fear extinction, to reduce the con- lack, M.D., is testing the SSRI Lexapro (es- studies that have looked at treatment patients, were physiologic responders, solidation of fear memories, and in a ra- citalopram) “at the next potential point of with the drug shortly after a traumatic reported Dr. Pitman and his associates tional way, to use medications to augment intervention”—in patients who, within a event. (Biol. Psychiatry 2002;51:189-92). the effects of psychotherapy,” he said. few weeks after trauma, are experiencing Forty-one patients were randomized The second study was a nonran- The study at Massachusetts General acute stress symptoms but do not meet in the emergency department at Mass- domized study of patients who were builds on a pilot study, published in 2002, the full criteria for PTSD. achusetts General Hospital to begin— treated in the emergency departments that suggested that posttrauma adminis- The possible mechanisms of action of within 6 hours of a traumatic event—a of two hospitals in France. Eleven pa- tration of propranolol in the emergency the SSRIs in such cases are not all clear, but 10-day course of propranolol (40 mg tients received propranolol for 7 days room may have a “preventive effect” on the hope is that the drugs will help inter- four times daily) or placebo. Eighteen (40 mg three times daily), with the subsequent PTSD. (See sidebar.) rupt the cycle of increased arousal and of the 41 received propranolol. first dose administered 2-20 hours af- anxiety that may predispose to full-blown Patients in the double-blind study ter the trauma and with a taper period Harvard/NIMH Study Design PTSD, said Dr. Pollack, director of the were instructed to return 1 and 3 of 8-12 days. They were compared Roger Pitman, M.D., who led the pilot hospital’s Anxiety and Traumatic Stress months later for assessment with the with 8 patients who refused propra- study and has a $2.5 million grant from Disorders Program. SSRIs are often used Clinician-Administered PTSD Scale nolol but agreed to participate. the National Institutes of Mental Health (with moderate success) today to treat (CAPS). At the 3-month follow-up, in- PTSD rates, as well as PTSD symp- to conduct the larger double-blind ran- syndromal PTSD. vestigators also measured patients’ tom scores, were higher in the patients domized study, hopes to recruit at least Physicians at the Center for the Study of physiologic responses during script-dri- who refused the drug (3 of 8) than in 100 patients who have both experienced Traumatic Stress at the Uniformed Health ven imagery of the traumatic event. patients who took it (1 of 11), report- a traumatic event and present with tachy- Services University of the Health Sciences At 1 month, the PTSD rate was 30% ed Guillaume Vaiva, M.D., of the Uni- cardia of at least 80 beats/min. in Bethesda, Md., have started a similar in the placebo group (6 of 20 patients versity of Lille (France), and his associ- According to Dr.