Patients who received a short course of propranolol in the wake of a traumatic event were less likely than placebo recipients to have a physiological response when thinking about their trauma, according to findings from a recent pilot study. Although the rate of posttraumatic stress disorder (PTSD) per se did not significantly differ between the two study groups, the findings do suggest that further exploration of preventive pharmacology for PTSD is warranted.

In many respects PTSD is an excellent choice for pharmacological prevention efforts. It is precipitated by a discrete, easily identifiable event, and preliminary psychophysiological studies have made gains in identifying which trauma patients are at risk for later PTSD (eg, those with elevated heart rates). Moreover, pharmacological treatment initiated after symptoms develop has shown only modest efficacy.

In 1996, a team of Israeli researchers reported that a course of benzodiazepine initiated within one to two weeks of a trauma did not prevent PTSD. However, a more viable candidate for PTSD prevention may be beta-adrenergic blockers such as propranolol. The reason, notes Roger K. Pitman, MD, Associate Professor of Psychiatry at Harvard Medical School and Massachusetts General Hospital in Boston, is that epinephrine (injected or endogenous) strengthens memory consolidation. Animal and human studies have shown that beta blockers hinder this process and thus might reduce the likelihood that epinephrine-laden trauma survivors will have recurrent, distressing memories of their experience. “The preclinical [literature] is really tight,” Dr. Pitman noted in an interview. “The question is the degree of applicability in a clinical setting, which we’re just starting to look at.”

10 DAYS OF TREATMENT

In the new study, reported in the January 15 issue of Biological Psychiatry, Dr. Pitman and colleagues randomly assigned 41 trauma victims to receive either propranolol (40 mg qid) or placebo for 10 days, followed by a nine-day taper. Treatment was initiated within six hours of the traumatic event; patients also received “supportive counseling” and were free to pursue other psychiatric or psychological care if they desired. All patients had a heart rate of at least 80 upon admission to the hospital emergency department but did not have severe physical injuries.

At a one-month follow-up evaluation (by which time some subjects had already dropped out), scores on the Clinician-Administered PTSD Scale were slightly lower in the propranolol group (27.6) than in the control group (35.5), though the difference was not statistically significant. However, nine of the 11 propranolol patients who remained in the study had a score below the placebo group median (P = .03). Two patients in the propranolol group (18%) and six of the 20 remaining placebo recipients (30%) met full criteria for PTSD.

Perhaps the most intriguing data came from a three-month follow-up session. Participants listened to their own taped verbal descriptions of the trauma and then imagined the event for 30 seconds; the researchers, meanwhile, measured subjects’ physiological response (heart rate, skin conductance, and electromyography). In this evaluation, six of the 14 placebo recipients (43%) but none of the propranolol recipients were “physiological responders” to mental imagery. Thus, although the study does not provide robust evidence of PTSD prevention, it does suggest that post-exposure treatment can attenuate the psychophysiological response to trauma.

It is possible that higher doses of propranolol would have yielded better results, the researchers noted. Moreover, the boundaries of the treatment window remain uncertain. “The traumatization doesn’t occur all at once,” Dr. Pitman pointed out. “People rehearse in their minds over and over again the traumatic events in the days and weeks following the trauma, and each time they do that they may further release adrenaline, which further consolidates the memory. If that’s the case, you may have a much longer window of opportunity.”

Dr. Pitman currently has a grant proposal under review to replicate the study using a much larger patient sample. “But as potentially exciting as this is,” he said, “the idea of secondary prevention of PTSD doesn’t hold a candle to primary intervention, which is preventing awful traumatic events from happening in the first place.”

—Peter Doskoch

Suggested Reading
1. Pitman RK, Sanders KM, Zusman RM, et al. Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry. 2002;51:189-192.

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