Pre-clinical and clinical studies suggest that acute, post-trauma (B-adrenergic blockade may abort the development of post-traumatic stress disorder (PTSD). Data from our published pilot study of 43 patients who presented to the Massachusetts General Hospital Emergency Department (ED) following an acute, psychologically traumatic event and who were randomly assigned to receive a 19-day course of either propranolol or placebo double-blind provide strong but inconclusive evidence that propranolol administered shortly after a traumatic event reduces the subsequent intensity of DSM-IV PTSD criterion B.5, viz., """"""""psychophysiological reactivity on exposure to internal ... cues that symbolize or resemble an aspect of the traumatic event."""""""" This pilot data also suggest that propranolol may reduce the rate and severity of the PTSD outcome in general. The primary objective of the proposed work is to perform a larger, placebo-controlled, double-blind study of the effect of post-trauma propranolol on psychophysiologic responses during script-driven imagery of the traumatic event. The secondary objective is to obtain further pilot data regarding the possible preventive effect of propranolol on subsequent PTSD symptom severity in general and the dichotomous diagnostic PTSD outcome. Patients will be men and women between the ages of 18 and 55 who have experienced a psychologically traumatic event meeting the DSM-IV A.1 and A.2 criteria with a heart rate of 80 BPM or greater upon presentation to the ED. As soon as baseline psychometric and psychobiologic measures have been collected, and no longer than six hours after the occurrence of the traumatic event, the patient will receive by mouth 40 mg of short-acting propranolol or placebo, and at the same time 60 mg of long-acting propranolol or placebo, which will be followed by ten days of 120 mg of longacting propranolol or placebo twice-daily as tolerated, with an additional medication taper period of nine days. One and three months following the traumatic event, the patient will undergo psychophysiologic, psychodiagnostic, and psychometric testing for PTSD.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (ZMH1-BRB-S (02))
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Tuma, Farris K
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Massachusetts General Hospital
United States
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Bhuvaneswar, Chaya G; Ruskin, Jeremy N; Katzman, Anna Roglieri et al. (2014) Pilot study of the effect of lipophilic vs. hydrophilic beta-adrenergic blockers being taken at time of intracardiac defibrillator discharge on subsequent PTSD symptoms. Neurobiol Learn Mem 112:248-52
Hoge, Elizabeth A; Worthington, John J; Nagurney, John T et al. (2012) Effect of acute posttrauma propranolol on PTSD outcome and physiological responses during script-driven imagery. CNS Neurosci Ther 18:21-7
Brunet, Alain; Orr, Scott P; Tremblay, Jacques et al. (2008) Effect of post-retrieval propranolol on psychophysiologic responding during subsequent script-driven traumatic imagery in post-traumatic stress disorder. J Psychiatr Res 42:503-6
Pitman, Roger K; Delahanty, Douglas L (2005) Conceptually driven pharmacologic approaches to acute trauma. CNS Spectr 10:99-106