The current state of post-traumatic stress disorder (PTSD mental hygiene consists largely of tertiary prevention of limited efficacy. Secondary prevention of PTSD, which to date has received little research attention, involves intervening in the aftermath of a traumatic event to forestall the disorder. Results of pre-clinical and clinical studies suggest that an acute post-traumatic hyperadrenergic state is involved in the pathogenesis of PTSD. Reduction of this hyperadrenergic state by means of beta-adrenergic blockade may prevent this disorder. The objective of the proposed work is to study the effectiveness of propranolol in preventing the development of PTSD in persons presenting to an emergency room (ER) following a traumatic event by means of a double-blind, placebo-controlled study. It is hypothesized that administration of propranolol to acutely traumatized patients in the ER and during the following days will reduce the rate of the PTSD outcome. Patients will be recruited from men and women between the ages of 18 and 65 who present to the Massachusetts General Hospital ER following an acute psychologically traumatic event and show evidence of a hyperadrenergic state as indexed by heart rate> 90. As soon as baseline psychometric and psychobiologic measures have been collected, the patient will receive the first dose of propranolol or placebo, which will be followed by ten days of twice-daily long-acting propranolol or placebo. One and three months following the traumatic event, the patient will undergo psychodiagnostic, psychometric, and psychophysiologic testing for PTSD. The 2 x 2 table of Drug (propranolol versus placebo) and three-month Outcome (PTSD versus no PTSD) will be tested for statistical significance by means of Pearson's Chi Square. Logistic regression will also be performed. Allowing for a 20 percent drop-out rate, 320 participants enrolled over a two and one-half year period and randomized on a 1:1 basis to propranolol or placebo will provide 80 percent power to detect a one-third or greater reduction by propranolol of the probability of the PTSD outcome.
