Brief reportPilot study of secondary prevention of posttraumatic stress disorder with propranolol
Introduction
Pharmacologic secondary prevention of posttraumatic stress disorder (PTSD) (i.e., intervening after a traumatic event to forestall PTSD’s development), is a topic of current medical interest that has received little investigation (Larkin 1999). Preclinical research has shown that epinephrine, exogenously administered or endogenously released, after a learning task strengthens memory consolidation and fear conditioning. This seems to be an adaptive mechanism whereby the significance of an experience facilitates its remembrance. The locus of this effect seems to be the amygdala (McGaugh 1990). The β-adrenergic blocker propranolol, which crosses the blood-brain barrier, administered pre- (Roozendaal et al 1997) or post- (Cahill et al 2000) training, abolishes this effect in animals and humans (Cahill et al 1994). The β-adrenergic blocker nadolol, which does not cross the blood--brain barrier, does not (van Stegeren et al 1998).
We have postulated that an excess of epinephrine release at the time of a psychologically traumatic event leads to overly strong emotional memory and fear conditioning that subsequently manifest themselves as PTSD symptoms (Pitman 1989). If this theory is correct, then administering propranolol soon enough after a traumatic event to block β-adrenergic receptors might have a preventive effect. We report here the results of a double-blind, placebo-controlled pilot study addressing this hypothesis.
Section snippets
Subjects
We recruited 41 Emergency Department (ED) patients who (a) had just experienced a traumatic event that met the DSM-IV PTSD A.1 (stressor) and A.2 (response) criteria; (b) had a heart rate (HR) of 80 beats per minute (BPM) or greater at the time of ED presentation; (c) were without serious physical injury, systolic blood pressure under 100 mm Hg, substance intoxication, pregnancy or lifetime history of congestive heart failure, heart block or bronchial asthma; (d) upon mental status examination
Pre-medication variables
Of 18 patients randomized to propranolol, eight (44%) were males and 13 (72%) had a motor vehicle accident (MVA) event. Of 23 patients randomized to placebo, 12 (52%) were males and 16 (70%) had a MVA event. Propranolol versus placebo group means (SDs) included: age (years), 34.3 (11.1) versus 34.3 (10.2); self-rated event severity (0–10 scale), 5.3 (1.5) versus 5.6 (2.2); self-rated response intensity (0–10 scale), 8.0 (1.7) versus 7.5 (2.8); time between traumatic event and first dose of
Discussion
The results of this pilot study support the clinical feasibility of testing the hypothesis that a course of propranolol begun shortly following an acute traumatic event is efficacious in reducing PTSD symptoms 1 month later. The pilot results also offer initial promise for this hypothesis, although conclusions must await adequately powered studies with larger samples. The observation that HR decrease from pre- to poststudy medication in the ED was comparable in the propranolol (11.8 BPM) versus
Acknowledgements
This work was supported by U.S. Public Health Service Grant #mxMH58671. The authors thank Drs. Yuchiao Chang, James McGaugh, Robert Parker, Scott Rauch and Rachel Yehuda for helpful suggestions and John Vetrano for pharmaceutical assistance.
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