Propranolol for the Treatment of Acute Stress Disorder
Information source: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Stress Disorders, Traumatic, Acute
Intervention: Propranolol (Drug)
Phase: Phase 2
Sponsored by: National Institute of Mental Health (NIMH)
This 10-week study will examine whether propranolol, a medication that blocks the activity
of the stress hormones adrenaline and noradrenaline, can relieve acute stress disorder (ASD)
and symptoms from persisting long-term. ASD is a condition that some people develop soon
after exposure to trauma. They may be anxious, depressed, have trouble sleeping, startle
easily, have difficulties concentrating, and feel as though the event is happening again.
Propranolol has been used for many years to treat high blood pressure and heart disease, and
has been found useful in treating anxiety states such as social phobia and migraine.
Men and women between 18 and 65 years of age who were recently exposed to trauma (between 1
and 3 weeks of evaluation in this study) may be eligible for this study. Candidates must be
diagnosed with ASD and must have been mentally healthy before the traumatic event. They
will be screened for the study with a medical and psychiatric interview, physical
examination, electrocardiogram (EKG), and blood and urine tests.
Participants will be evaluated with the following procedures:
- Neuropsychological tests using pen-and-paper and computer tests to evaluate cognitive
function, particularly memory, learning, attention and concentration, and vocabulary
- Emotion-related performance tasks to determine if the study medication can weaken
emotionally arousing information by blocking the activity of adrenaline and
noradrenaline. Subjects perform emotion-related and neutral tasks, such as looking at
pictures with neutral, pleasant, or unpleasant content, both before and after treatment
with the study medication (see below).
- Traumatic script exposure: Subjects recount the traumatic event that caused them to
develop ASD. The description is summarized, recorded, and played back to the subject.
During the playback, physiological responses, such as heart rate and skin conductance
(sweating), are recorded using electrodes taped to the hand and chest.
- Fear conditioning to evaluate the response to an unpleasant stimulus: Several mild
electrical shocks are delivered to the wrists while the subject looks at colored
squares. Heart rate and skin conductance are measured.
- Magnetic resonance imaging (MRI) to examine brain structure. The subject lies on a
table that is moved into the MRI scanner (a narrow cylinder containing a strong
magnetic field) and must remain still during the actual scanning. Earplugs are worn to
muffle loud noises caused by electrical switching of radio frequency circuits used in
the scanning process.
After the evaluation, participants are randomly assigned to receive either propranolol or
placebo (a look-alike pill with no active ingredient) for 8 weeks During this time they are
seen by a doctor once a week for 4 weeks and then once every other week for the rest of the
study. At the end of the 8-week treatment period, participants undergo the same evaluation
they had before beginning treatment (see above). The decision to continue treatment will
then be decided based on the individual's clinical condition and whether he or she received
propranolol or placebo.
Official title: Propranolol For the Treatment of Acute Stress Disorder
Study design: Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment
The effects of exposure to severe stress differ between individuals. Still, a typical
response pattern consisting of increased anxiety and arousal, sleep difficulties,
preoccupation with and re-experiencing of the traumatic event is the rule. In most trauma
survivors the severity of this condition diminishes within days or weeks. Still, in some
cases psychopathology persists, and can lead to severe and chronic PTSD. The diagnosis of
"Acute Stress Disorder" (ASD) was introduced in DSM-IV, addressing psychopathology between 2
days and 1 month of exposure to trauma. It has been shown that 60%-80% of patients who meet
criteria for ASD will go on and suffer from PTSD. Nevertheless, pharmacological trials in
PTSD have only been performed, with few exceptions, in chronic populations. Chronic PTSD has
emerged as a treatment resistant condition, with only partial response to treatment with
antidepressant and anxiolytic agents. Therefore, the potential benefits of early treatment
intervention in this condition could be immeasurable.
A principal model proposed to explain the initiation and perpetuation of PTSD is the
fear-conditioning model. It assumes that intrusive, involuntary, repetitive, vivid
emotionally laden memories of the trauma are pivotal to the development of the disorder.
Although such memories are a part of the early trauma response, in healthy trauma survivors
these memories gradually lose their intrusive quality and much of their emotional charge,
allowing recovery. In PTSD this process does not occur. The impediment to recovery may
result from deeper encoding and consolidation of the traumatic memories inhibiting the
normal process of extinction that is part of the healthy processing of the traumatic event.
Animal and human research has conclusively shown that emotionally charged stimulation is
remembered better than less emotionally arousing information. Animal and human data show
that catecholamines, particularly norepinephrine, augment consolidation of emotional memory.
Furthermore, administration of catecholamine receptor blockers cancels the enhanced memory
for emotional, compared to non-emotional, information. These data suggest that
administration of catecholamine receptor blockers soon after trauma may obstruct
consolidation of emotional memories, thereby preventing or alleviating posttraumatic
symptomatology. Treatment experience in humans is limited to the administration of
propranolol in single case descriptions and a pilot prevention study that was not
sufficiently powered to allow a definite inference. However, the overall impression from
administration of propranolol in the early time period after trauma is positive. In light of
the neurophysiology and preliminary data presented above, we propose a prospective,
randomized placebo controlled study of propranolol treatment in ASD.
Minimum age: N/A.
Maximum age: N/A.
1. Exposure to trauma between 1 and 3 weeks of evaluation.
2. Traumatic event involving at most minor physical injury (i. e., release from the ER
within 12 hours of admission, without surgical intervention).
3. Mentally healthy prior to trauma exposure.
4. DSM-IV diagnosis of ASD.
5. CAPS score equal or greater than 40.
6. Eighteen-65 years old, in good physical health as confirmed by a complete physical
exam (including normal vital signs), electrocardiogram, neurological exam, and
routine laboratory tests of blood and urine. (However, if patients have had blood
work through the ER or their primary MD within the last 6 months, these results will
be used instead of repeating blood draws for inclusion into the study).
7. Male and female.
8. Capable of providing informed consent, obtained prior to any study procedures.
9. Free of all psychotropic medication for at least 1 week, excluding short-term
1. Any DSM IV Axis I diagnosis preceding exposure to trauma. In order to compare a
homogenous subject group we require all participants to be physically and mentally
healthy before exposure to trauma.
2. Treatment with psychotropic medication other than short acting hypnotic or sedative
medication since exposure to trauma. Allowing such treatment acknowledges patient
distress and ensures administration of minimal level of care. Short acting
medications enables having patients free of medication when absolutely necessary.
3. History of traumatic brain injury involving loss of consciousness for at least 20
minutes or anterograde amnesia for at least 24 hours.
4. Blood pressure over 150/100 or under 100/60 (applicable for either systolic or
diastolic measures). Pulse over 100 or under 60 per minute.
5. Cardiac arrhythmia, coronary artery disease or any cardiac dysfunction with a
potential to develop congestive heart failure.
6. Bronchospastic pulmoray disease, chronic obstructive pulmonary disease or any active
7. Raynaud phenomenon. Potential participants with other immune vasculitis will be
referred to internal medicine consult.
8. Risk factors for coronary artery disease: Family history, diabetes, hyperlipidemia,
hypertension, peripheral vascular disease or physical signs suggestive of cardiac
compromise. Any questionable case will be referred to internal medicine consult.
9. Treatment with any adrenergic compound, prescription or over-the-counter (OTC; for
example, preparations containing yohimbine sold OTC).
10. Unable to comply with study procedures or assessments.
11. Patients at current risk for homicide or suicide.
12. Litigation before or during the study. Seeking compensation so soon after trauma,
before or during any treatment trial, may represent ambivalence in the true
motivation for cure.
13. Patients who meet DSM-IV criteria for substance abuse (alcohol or drugs) or
dependence within 6 months prior to screening.
14. Women of childbearing potential who are not practicing a clinically accepted method
of contraception or who have a positive pregnancy test or who are lactating.
15. Patients suffering from any major chronic physical disorder not specifically
mentioned here, even if stable, will have to be individually approved by the PI or
another participating MD.
Locations and Contacts
National Institute of Mental Health (NIMH), Bethesda, Maryland 20892, United States
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Bryant RA, Sackville T, Dang ST, Moulds M, Guthrie R. Treating acute stress disorder: an evaluation of cognitive behavior therapy and supportive counseling techniques. Am J Psychiatry. 1999 Nov;156(11):1780-6.
Foa EB, Riggs DS, Gershuny BS. Arousal, numbing, and intrusion: symptom structure of PTSD following assault. Am J Psychiatry. 1995 Jan;152(1):116-20.
Starting date: September 2003
Last updated: March 3, 2008