Elsevier

Biological Psychiatry

Volume 51, Issue 2, 15 January 2002, Pages 189-192
Biological Psychiatry

Brief report
Pilot study of secondary prevention of posttraumatic stress disorder with propranolol

https://doi.org/10.1016/S0006-3223(01)01279-3Get rights and content

Abstract

Background: Preclinical considerations suggest that treatment with a β-adrenergic blocker following an acute psychologically traumatic event may reduce subsequent posttraumatic stress disorder (PTSD) symptoms. This pilot study addressed this hypothesis.

Methods: Patients were randomized to begin, within 6 hours of the event, a 10-day course of double-blind propranolol (n = 18) versus placebo (n = 23) 40 mg four times daily.

Results: The mean (SD) 1-month Clinician-Administered PTSD Scale (CAPS) score of 11 propranolol completers was 27.6 (15.7), with one outlier 5.2 SDs above the others’ mean, and of 20 placebo completers, 35.5 (21.5), t = 1.1, df = 29, p = .15. Two propranolol patients’ scores fell above, and nine below, the placebo group’s median, p = .03 (sign test). Zero of eight propranolol, but six of 14 placebo, patients were physiologic responders during script-driven imagery of the traumatic event when tested 3 months afterward, p = .04 (all p values one-tailed).

Conclusions: These pilot results suggest that acute, posttrauma propranolol may have a preventive effect on subsequent PTSD.

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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