Evidence-Based Reviews

Can medications prevent PTSD in trauma victims?

Current Psychiatry. 2007 September;6(9):47-55

Murray W. R. Bennett, MD, FRCPC

Douglas Zatzick, MD

Peter Roy-Byrne, MD

Extinguishing the process that trauma sets in motion may avoid chronic anxiety.

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References

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Posttraumatic stress disorder (PTSD) is a preventable mental illness—without trauma, the illness does not occur. Primary prevention (such as eliminating war, rape, physical assaults, child abuse, or motor vehicle accidents) would be effective but is an unrealistic goal. Secondary prevention (such as preventing PTSD after individuals have been exposed to trauma) may be attainable.

No medication is FDA-approved to prevent PTSD, but patients recently exposed to trauma might benefit from drugs approved for other indications. Possibilities include noradrenergics such as propranolol, corticosteroids that affect the hypothalamic-pituitary-adrenal (HPA) axis, opioids, benzodiazepines, and antidepressants. Some investigational agents also might block the process that turns a traumatic experience into PTSD.

This article discusses these intriguing ideas and suggests which trauma victims might benefit now from acute pharmacologic PTSD prevention.

Who might be treated?

An estimated 8% to 10% of the U.S. population experiences PTSD at some point in life (Box 1).^1,2 A person’s risk of developing PTSD after a traumatic event depends on the type of trauma. For example, 10% of motor vehicle accident survivors develop PTSD, compared with 60% of rape survivors.¹

Targeting anyone who has experienced trauma for secondary PTSD prevention would expose large groups of people to medications they do not need. Targeting selected persons who are at the highest risk would be more efficient and cost-effective. In a group of acute trauma-exposed persons, 2 selection criteria could be considered simultaneously:

Which patients may be most predisposed to PTSD?
Which patients are showing early symptoms that may predict PTSD?

Box 1

PTSD: From short-term to chronic distress

More than half of all American adults have been exposed to at least one traumatic event at some point in their lives.¹ In most persons, the posttraumatic stress reaction causes short-term distress, with hyperarousal, agitation, intrusive memories, and exaggerated startle. Although these symptoms usually subside relatively quickly, they persist and evolve into posttraumatic stress disorder (PTSD) in a substantial number of trauma victims.

An estimated 8% to 10% of the U.S. population experiences PTSD at some point in life.² Emotional distress, social and occupational disability, and persistent decrements in quality of life make PTSD a major public health problem.

Risk factors and resiliency. Certain factors have been shown to increase a person’s vulnerability for PTSD (Table 1).³ Other proposed risk factors include:

personality types⁴
psychophysiologic factors such as reactivity, conditionability, and resistance to extinction/habituation.⁵

Clinical Point

Trauma-related predictors of PTSD appear to include acute excessive arousal and fear, dissociation, and depression

Strong evidence also indicates that acute trauma-related symptoms—including excessive arousal and fear,⁶ peritraumatic dissociation, and depression—predict the later development of PTSD.

Once identified, individuals predisposed to developing PTSD could be given treatment to increase their resiliency after they have been exposed to trauma. Early evidence suggests that you also could consider giving these patients medications as secondary prevention (Table 2).

Table 1

Who develops PTSD? Risk and resiliency factors

Risk factors that may increase vulnerability for PTSD Diminished cognitive ability History of difficult childhood trauma, such as loss of a parent Genetic endowment History of abuse and neglect Trauma severity Limited social support Continued exposure to stress and trauma
Resiliency factors that may protect against PTSD Self-efficacy Cognitive ability and flexibility Optimism Moral compass or strong set of beliefs Faith and spirituality
Source: Reference 3

Table 2

Medications being studied for PTSD prevention

Mechanism of action	Medication		FDA-approved indications
			Psychiatric	Nonpsychiatric
Noradrenergic	Clonidine		No	Yes
	Guanfacine		No	Yes
	Prazosin		No	Yes
	Propranolol		No	Yes
Hypothalamic-pituitary-adrenal axis	Hydrocortisone		No	Yes
Opioid	Morphine		No	Yes
Antidepressant	Dual action	Duloxetine	Yes	Yes
	Dual action	Venlafaxine	Yes	No
	SSRIs	Citalopram	Yes	No
		Fluoxetine	Yes	No
		Paroxetine	Yes	No
		Sertraline	Yes	No
	TCAs	Amitriptyline	Yes	No
	TCAs	Imipramine	Yes	No
GABA-benzodiazepine	Alprazolam		Yes	No
GABA-benzodiazepine	Temazepam		Yes	No
Corticotropin-releasing hormone (CRH)	CRH antagonist		Investigational
Substance P	Substance P antagonist		Investigational
Neuropeptide Y	Neuropeptide Y agonist		Investigational
SSRIs: selective serotonin reuptake inhibitors
TCAs: tricyclic antidepressants

Targeting noradrenergic activity

Increased noradrenergic activity has been associated with persistent memories and PTSD. Therefore, medications that reduce noradrenergic tone by blocking receptors or reduce norepinephrine release are being explored for PTSD prevention.

Propranolol. Three small studies have examined whether the beta-noradrenergic receptor blocker propranolol can prevent PTSD.

In a randomized, double-blind, placebo-controlled trial,⁷ 41 emergency department patients who had a heart rate of ≥ 80 bpm within 6 hours of a traumatic accident received propranolol, 40 mg qid, or placebo for 10 days. After 1 month, the 11 patients who completed propranolol treatment showed a nonsignificant trend toward lower scores on the Clinician-Administered PTSD Scale (CAPS), compared with 20 patients taking placebo. At 3 months, the propranolol group had less physiologic reactivity (as measured by heart rate and skin conductance) to trauma-related cues than the placebo group.

In a nonrandomized study,⁸ PTSD developed within 2 months in 1 of 11 trauma victims who agreed to take propranolol, 40 mg tid, immediately after the trauma, compared with 3 of 8 victims who refused the medication.

In an unpublished randomized, double-blind trial,⁹ 48 patients admitted to a level I trauma center received propranolol, 40 mg tid; gabapentin, 400 mg tid; or placebo for PTSD prevention. Gabapentin was chosen because it has few side effects or metabolic interactions and preliminary evidence of anxiolytic efficacy.