Powered by the Evidence-based Practice Centers
Evidence Reports All of EHC
Evidence Reports All of EHC



Interventions for the Prevention of Post-traumatic Stress Disorder in Adults After Exposure to Psychological Trauma

Research Protocol ARCHIVED Jun 6, 2012
Download PDF files for this report here.

Page Contents

On July 27, 2012, September 26, 2012, and November 8, 2012, several amendments were made to this protocol. To view these amendments, please see the section titled “Summary of Protocol Amendments.”

Background and Objectives for the Systematic Review

Studies suggest that individuals experience a broad range of traumatic events throughout their lives and that the frequency of these events may vary by the group studied, for example, civilian versus noncivilian samples. The fourth edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) defines a traumatic event as an event experienced, witnessed, or confronted by a person that involves (a) actual or threatened death, (b) serious injury, or (c) a threat to the physical integrity of self or others.1 The DSM-IV-TR diagnosis of PTSD also requires that the person’s response to the event involve intense fear, helplessness, or horror. Traumatic events may include military combat, violent personal assault, being taken hostage, a terrorist attack, torture, natural or manmade disasters, and being diagnosed with a life-threatening illness.1 The full DSM-IV-TR criteria are listed in Table 1.

Table 1. Diagnostic criteria (DSM-IV-TR) for post-traumatic stress disorder
Criterion Symptom or description
Criterion A: Trauma (both)
  • Traumatic event that involved actual or threatened death, serious injury, or threat to physical integrity
  • Intense response of fear, helplessness, or horror
Criterion B: Re-experiencing symptoms: (one or more)
  • Intrusive recollections of events
  • Recurrent distressing dreams of the event
  • Acting or feeling as if the traumatic event were recurring
  • Distress at internal or external reminders of the trauma
  • Physiological reaction to internal or external reminders
Criterion C: Persistent avoidance and numbing (three or more)
  • Avoidance of thoughts, feelings, or conversations associated with trauma
  • Avoidance of activities, places, or people that arouse recollections of trauma
  • Failure to recall an important aspect of trauma
  • Loss of interest or participation in significant activities
  • Detachment from others
  • Restricted range of affect
  • Lost sense of the future
Criterion D: Hyperarousal (two or more)
  • Difficulty falling or staying asleep
  • Irritability or outburst of anger
  • Difficulty concentrating
  • Hypervigilance
  • Exaggerated startle response
Criterion E: Duration of disturbance
  • Duration of disturbance symptoms is more than 1 month
Criterion F: Clinically significant distress or impairment
  • Disturbance causes clinically significant distress or impairment in social, occupational, or other important areas of function

Prevalence of Traumatic Events

Studies conducted in the 1990s attempted to identify and describe the prevalence of traumatic events in nonclinical samples. Resnick et al.2 found that lifetime exposure to any type of traumatic event was 69 percent in a sample of 4,008 adult U.S. women. The National Comorbidity Survey3 indicated that 60 percent of men and 51 percent of women reported experiencing at least one traumatic event in their lifetimes.

Most of the research has focused on assessing the burden of trauma in different populations. Not surprisingly, studies among groups at risk of occupational exposure to trauma, such as police officers, firefighters, and military service members, have shown high rates of trauma exposure.4 Several studies have examined the prevalence of traumatic events among college students. These studies all showed that exposure to traumatic events was common, with lifetime prevalence ranging from 39 to 84 percent.5-7

Development of Post-traumatic Stress Disorder and the Rationale for Preventing It With Early Intervention

Many theories focus on the role of disturbances in memory (i.e., problems with memory formation, retrieval, bias, saliency, etc.), and argue that alterations in the normal processes of memory are key to understanding the development and maintenance of PTSD. One of these theories suggests that when trauma-related memories are not properly integrated into memory, individuals may re-experience symptoms of PTSD.8

Intense affect during a traumatic event and its accompanying physiological arousal have been associated with the development of PTSD.9,10 Dissociation or detachment during the event has also been found to be a significant predictor of PTSD.9 In extreme threat situations, strong affect can result in dissociation and prevent trauma-related information from being fully consolidated within memory. Incomplete memory consolidation may cause an individual to retain a limited amount of information about the event and/or may make the memory less accessible. The ability to access full or complete trauma-related memories is a core feature of several psychological theories of PTSD prevention and/or treatment.

Stress hormones released during exposure to a traumatic event have also been implicated in the development of PTSD. Some studies have shown that elevated levels of cortisol and adrenaline can disrupt the normal formation of memories, while others have found that stress hormones enhance memory consolidation.11,12

Cognitive theories of PTSD are based on the concept that information associated with a traumatic event is inconsistent with the information contained in an individual’s core cognitive schema. An individual exposed to a traumatic event tries to make sense of the experience but has difficulty fully integrating it into his/her existing schema. Over time, this disintegration manifests itself in the symptoms and behaviors classified as PTSD. Maladaptive beliefs related to the traumatic event have also been identified as a risk factor for the development of PTSD.13

The implications of these various theories provide a rationale for a myriad of early intervention strategies, but they are only one part of the puzzle. Variability of types of trauma, contexts in which they occur, and individual differences of those exposed to traumatic events are likely to prohibit a one-size-fits-all model for preventive intervention.

Potential Preventive Interventions

Potential preventive interventions span a variety of psychological and pharmacological domains. These interventions have been used both separately and in combination with one another.

Psychological Interventions

Specific psychological interventions that have been studied for the prevention of adult PTSD are described below and include the following: psychological debriefing interventions, including critical incident stress debriefing (CISD) and critical incident stress management (CISM); psychological first aid (PFA); trauma-focused cognitive-behavioral therapy (CBT); cognitive restructuring therapy; cognitive processing therapy; exposure-based therapies; coping skills therapy (including stress inoculation therapy); psychoeducation; normalization; and eye movement desensitization and reprocessing (EMDR). These therapies are designed to prevent the onset of PTSD and development of trauma-related stress symptoms soon after exposure to a traumatic event.

Psychological Debriefing, Critical Incident Stress Debriefing, and Critical Incident Stress Management

Psychological debriefing interventions aim to educate victims about normal reactions to trauma and to encourage them to share their experiences and emotional responses to the event. Debriefing is typically offered in a single session within hours or days after the event to everyone exposed to the event. Although several variations of these single-session interventions have been tested, the most common form of psychological debriefing is CISD.14

CISD is a secondary prevention intervention originally developed for use with individuals indirectly exposed to traumatic events because of their occupation, such as firefighters or emergency medical personnel. CISD is administered in a single 3- to 4-hour session by a team composed of individuals familiar with the organization (e.g., officers within a police department) and mental health professionals.15,16 In addition to helping normalize the responses of individuals to stress and encouraging them to talk about their experiences and reactions, the team teaches coping skills and offers additional resources for those who may need it.17 By design, the CISD approach is flexible and loosely structured. CISD was not designed to prevent PTSD; nonetheless, it has been applied directly to victims of trauma despite evidence that it may be ineffective for that purpose and actually may have harmful effects.18-20 A 2002 update of a previous 1997 Cochrane review assessed the effectiveness of brief, single-session psychological debriefing for the management of psychological distress after trauma and the prevention of PTSD.21

CISD has expanded to become CISM, a multicomponent, comprehensive crisis intervention program that aims to reduce the severity of, and related impairment associated with, traumatic stress.18 CISM incorporates additional methods such as pre-incident training for people with high-risk occupations, one-on-one individual crisis support, demobilizing (i.e., information about coping and stress to large groups of emergency workers as they rotate off duty), and defusing (small-group interventions during which participants are asked to explore and discuss the incident and their emotional reactions to it).15 CISM also has a family support component whereby family members of the emergency personnel are debriefed. Lastly, there are additional procedures for referring people for psychological services.18

PFA is a systematic set of helping actions aimed at reducing initial post-trauma distress and supporting short- and long-term adaptive functioning. PFA is designed as an initial component of a comprehensive disaster/trauma response, and it is constructed around eight core actions: (1) contact and engagement, (2) safety and comfort, (3) stabilization, (4) information gathering, (5) practical assistance, (6) connection with social supports, (7) information on coping support, and (8) linkage with collaborative services.22 PFA is concept driven and its application requires assessment and clinical judgment by the provider given the complexity of presentations, variability of context, need, and logistical constraints. PFA is intended for use by disaster mental health responders, counselors, and others who may provide immediate support for trauma survivors. Two major advantages of PFA are that it is highly portable and designed for delivery anywhere recent trauma survivors can be found—such as shelters, schools, hospitals, homes, staging areas, feeding locations, family assistance centers, and other community settings. The principles of PFA can also be applied immediately after a traumatic event in nondisaster field settings, including hospital trauma centers, rape crisis centers, and war zones.23

CBT uses principles of learning and conditioning to treat disorders and includes components from both behavioral and cognitive therapy. In trauma-focused CBT, components such as exposure, cognitive restructuring, and various coping skills have been used either alone or in combination with one another. Most forms of trauma-focused CBT are brief and involve weekly sessions lasting 60 to 90 minutes, although the number of sessions varies across studies. CBT can be administered either as group or individual therapy.24-26

Exposure-based therapy involves confrontation with frightening stimuli and is continued until anxiety is reduced. The exposure is based on mental imagery from memory or introduced in scenes presented by the therapist (imaginal exposure). In some cases, exposure is from the actual scene or similar events in life (in vivo exposure). The aim is to extinguish the conditioned emotional response to traumatic stimuli (for the subject to learn that nothing “bad” will happen during traumatic events), which eventually reduces or eliminates avoidance of feared situations and the affect associated with it. Exposure therapy is typically conducted for 8 to 12 weekly or biweekly sessions lasting 60 to 90 minutes.24,25,27

Cognitive restructuring is based on the theory that the interpretation of the event, rather than the event itself, determines an individual’s mood. It aims to facilitate relearning thoughts and beliefs generated from a traumatic event and increase awareness of dysfunctional trauma-related thoughts and correct or replace those thoughts with more adaptive and/or rational cognitions. Cognitive restructuring generally takes place over 8 to 12 sessions of 60 to 90 minutes.24,25

Coping skills therapy may include components such as stress inoculation therapy, assertiveness training, biofeedback (including brainwave neurofeedback), or relaxation training. All may use techniques such as education, muscle relaxation training, breathing retraining, role playing, et cetera, to manage anxiety or correct misunderstandings conditioned at the time of trauma. The therapy is designed to increase coping skills for current situations. Most types of coping skills therapies require at least eight 60- to 90-minute sessions, while more comprehensive interventions such as stress inoculation therapy require 10 to 14 sessions.24, 25

EMDR combines imaginal exposure with the concurrent induction of saccadic eye movements that are believed to help reprogram brain function so that emotional impact of trauma can be resolved. In the EMDR process, the client is instructed to imagine a traumatic memory, engage in negative cognition, and then articulate an incompatible positive cognition (e.g., personal worth). The clinician asks the client to contemplate memory while focusing on rapid movement of the clinicians’ fingers. After 10 to 12 eye movements (back and forth), the clinician asks the client to rate the strength of the memory and his or her belief in the positive cognition. Although earlier versions of EMDR consisted of 1 to 3 sessions, current standards consist of 8 to 12 weekly sessions of 90 minutes each.24, 28

Pharmacological Interventions

Various neurobiological pathways have been implicated in the development of PTSD. Accordingly, pharmacotherapy has been tried as a preventive intervention for PTSD. Several drugs have been studied for PTSD prevention including propranolol, morphine, glucocorticoids, and selective serotonin-reuptake inhibitors (SSRIs).11,26


A significant body of research suggests that PTSD is associated with hyper-reactivity of the sympathetic nervous system, specifically the noradrenergic system. Studies have repeatedly shown that heart rates are elevated in the peritraumatic event period among persons exposed to trauma who develop PTSD, that stress-induced norepinephrine levels are higher among persons with PTSD, and that corticotrophin-releasing factor, which stimulates release of norepinephrine, is elevated among people with PTSD.29

Propranolol, a beta-adrenergic antagonist that crosses the blood-brain barrier, has been evaluated in several studies for its ability to prevent PTSD.30-32 So far results have failed to show any clear benefit of propranolol, when compared with placebo, in reducing physiological reactivity during traumatic imagery, severity of PTSD symptoms, or the rate of the PTSD diagnostic outcome. In addition, significant controversy exists about the use of propranolol for PTSD prevention because of its ability to attenuate the emotional response and memory of a traumatic event. Studies have shown that propranolol not only decreases emotional memory but also episodic memory for the traumatic event.33 This effect leads to various ethical concerns, considering that the long-term implications of emotional and episodic memories are not yet well understood.


The opiate analgesic, morphine, has shown promise in preventing PTSD in persons experiencing physical injury from a traumatic event. In 155 adults hospitalized after traumatic injury, those prescribed higher doses of morphine had lower incidence of PTSD at 3-month followup.34 In 696 combat-injured U.S. military personnel serving in Iraq, the use of morphine during early trauma care was associated with significantly lower risk of a subsequent PTSD diagnosis.35 These studies highlight and support the importance of pain control in physically injured persons, but the potential role of opiates in prevention of PTSD after severe psychological trauma in the absence of painful physical injury remains unclear.


A substantial body of research has suggested that alterations in the hypothalamic-pituitary-adrenal (HPA) axis are associated with PTSD. Much of the research suggests increased sensitivity of the HPA negative feedback loop between the release of corticotropin-releasing factor (CRF) from the hypothalamus and release of cortisol from the adrenal cortex, resulting in high levels of CRF and low levels of cortisol among people with PTSD.29 This has led to the hypothesis that exogenous administration of cortisol shortly after trauma may prevent PTSD by preventing development of HPA axis dysregulation.

Several naturalistic studies have found that patients who were administered glucocorticoids either during or immediately after the trauma were significantly less likely to develop PTSD than those who were not.36,37 These studies were conducted naturalistically in settings where multiple variables, including the administration of other medications and treatment procedures, could not be controlled.

Selective Serotonin-Reuptake Inhibitors

SSRI antidepressants are currently the drugs most widely used to treat PTSD. SSRIs have been shown to be modestly effective for civilian trauma-related PTSD, but no more effective than placebo for PTSD in military veterans.38,39 As with beta-blockers such as propranolol, SSRIs may diminish the more severe clinical sequelae after a stress exposure, possibly through nonspecific effects on other monoamines, through neuroprotective effects in the brain, or through increases in neurotrophic factors that can block the down-regulation of brain-derived neurotrophic factors.40

Table 2 provides a summary of the medications studied for the prevention or treatment of PTSD.

Table 2. Medications studied for the prevention or treatment of post-traumatic stress disorder
Class Drug
Selective serotonin-reuptake inhibitors citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline
Serotonin and norepinephrine reuptake inhibitors duloxetine, desvenlafaxine, and venlafaxine
Other second-generation antidepressants bupropion, mirtazapine, nefazodone, and trazodone
Tricyclic antidepressants imipramine, amitriptyline, and desipramine
Monoamine oxidase inhibitors phenelzine, isocarboxazid, selegiline, and tranylcypromine
Alpha-blockers prazosin
Beta-blockers propranolol
Benzodiazepines alprazolam, diazepam, lorazepam, and clonazepam
Anticonvulsants topiramate, tiagabine, lamotrigine, carbamazepine, divalproex, and gabapentin
Nonbenzodiazepine sedatives/hypnotics zolpidem, eszopiclone, rozerem, and zaleplon
Second-generation (atypical) antipsychotics olanzapine and risperidone
Narcotic medication morphine
Steroids hydrocortisone
Opioid antagonists naltrexone

Emerging Interventions

In addition to traditional psychological and pharmacological interventions, there is a growing variety of emerging interventions and approaches derived from complementary and alternative medicine (CAM). Among these are dietary supplements, yoga, and guided imagery.41 The use of CAM practices to prevent PTSD is novel, and as a result, their efficacy remains unclear.

Prevention Intervention Outcomes

One of the primary outcomes in the PTSD-prevention intervention literature is lack of trauma-related symptom development, which includes both clinician-rated and self-reported measures. In addition, we will consider other health outcomes such as symptom reduction; prevention/reduction of comorbid medical or psychiatric conditions (e.g., depressive symptoms, anxiety symptoms); improved quality of life; or ability to return to work or return to active duty. If we cannot find data on a particular health outcome of interest, we will include surrogate outcomes if evidence of a causal relationship between surrogate and health outcomes is available.

Summary of Existing Guidance

A recent review assessed the evidence base for existing guidelines for PTSD from seven respected organizations in the United States, Australia, and Europe.42 These organizations include the American Psychiatric Association (APA), the U.S. Department of Veterans Affairs/Department of Defense (VA/DOD), the National Institute of Clinical Excellence (NICE), the National Health and Medical Research Council (NHMRC), the International Society for Traumatic Stress Studies (ISTSS), the American Academy of Child and Adolescent Psychiatry (AACAP), and the Institute of Medicine (IOM). The review investigated whether each of the guidelines was based on existing evidence and concluded that the empirical data were insufficient to support many of the guidelines and recommendations put forth by these organizations.

Nonetheless, the clinical practice guidelines named above provide very similar recommendations regarding prevention of PTSD. Five of the seven sets of guidelines (VA/DOD, APA, NICE, NHMRC, ISTSS for adults, and ISTSS for children and adolescents) address early preventive interventions for populations exposed to trauma. They each warn against the use of psychological debriefing interventions to prevent the onset of PTSD, and four sets (APA, NICE, NHMRC, and ISTSS for adults) describe alternative approaches.42 The NICE guidelines suggest offering “practical social and emotional support” to trauma survivors; whereas, the NHMRC guidelines suggest provision of psychological first aid based on expert consensus and the ISTSS guidelines support “practical, pragmatic psychological support and information.”42, p. 548 The APA guidelines state that the use of early supportive interventions, psychoeducation, and case management may be helpful for acutely traumatized individuals because they “promote engagement in ongoing care and may facilitate entry into evidence-based psychotherapeutic and psychopharmacological treatments [II].”43, p. 13 In addition, the APA guidelines report that there is only minimal evidence that early supportive care alone can lead to long-term reductions in PTSD symptoms in populations of patients exposed to multiple recurrent traumas. On the other hand, there is no evidence of harms due to early supportive care.

Rationale and Objective of the Review

Psychological trauma is common and leads to PTSD in a substantial number of individuals exposed to trauma. Prevention of PTSD, therefore, has the potential to reduce a significant burden of individual and societal suffering. Unlike most psychiatric disorders, the precipitating cause of PTSD, psychological trauma, is an identifiable event that has a known time and place of onset. Therefore, the people at risk of developing PTSD (i.e., those exposed to trauma) can be identified, and preventive interventions can be offered to them shortly after exposure.

Despite evidence that some early interventions are not effective in preventing PTSD, or might even cause harm, they are still widely used. Such use indicates that uncertainty and controversy still exist within the field about providing an intervention that intuitively seems like it should help, and also that not enough consideration is given to scientific evidence when weighing intervention benefits and harms.

The objective of this review is to systematically evaluate the evidence on the general and comparative effectiveness and risk of harms of early interventions to prevent PTSD in people who have experienced psychological trauma. The report will also take into account the unique nature of different types of trauma and moderators affecting the impact of traumatic exposure. We will develop an analytic framework that will help conceptualize interventions to prevent PTSD.

This evidence review will be part of a collection of reports produced by the Agency for Healthcare Research and Quality (AHRQ) for a three-part series focusing on the treatment of PTSD in populations exposed to trauma. These reports will critically assess the comparative effectiveness of selected interventions aimed at treating symptoms of PTSD in adults and children and of interventions to prevent the development of PTSD in adults exposed to psychological trauma.

Note: This protocol includes revisions to the Key Questions (KQs) suggested by our Key Informants and revisions to the PICOTS (specifically the minimum sample size of 100 for prospective cohort studies, the addition of monoamine oxidase inhibitors and nonbenzodiazepine sedatives/hypnotics to the list of pharmacological interventions, and changing the name of the pharmacological interventions table) suggested by members of our Technical Expert Panel (TEP) and the project team. We posted the draft KQs for public comment on January 4, 2012. We received one comment on January 8, but it applied to another AHRQ-supported report in progress that addresses the psychological and pharmacological treatments for adults with PTSD.

Key Questions

KQ 1: For adults exposed to psychological trauma, what is the absolute effectiveness or comparative effectiveness of early interventions to prevent PTSD or to improve health outcomes?

KQ 2: For adults exposed to psychological trauma, does timing, intensity, or dosage of intervention have an impact on the effectiveness or harms of approaches to prevent PTSD or to improve health outcomes?

KQ 3: For adults exposed to psychological trauma, how does efficacy, effectiveness, or harms of early interventions to prevent PTSD differ for characteristics of traumatic exposure or subpopulations with respect to:

  • Demographic groups (defined by age, ethnic and racial groups, and sex);
  • Psychiatric comorbidities; or
  • Personal risk factors for developing PTSD (e.g., having a diagnosis of acute stress disorder vs. not having the diagnosis)?

KQ 4: For adults exposed to psychological trauma, what are the absolute risks or comparative risks of harms from early interventions to prevent PTSD?

PICOTS Criteria

The population, interventions, comparators, outcome measures, timing, and setting (PICOTS) criteria for the preceding KQs are:


  • Adults exposed to psychological trauma (to include interpersonal or domestic violence/abuse, sexual abuse/assault/rape, combat/military-related trauma, crime-related events, terrorism, natural disasters, injury, life-threatening illness or medical procedures, witnessing a traumatic event, being a refugee, and asylum seeking) at risk of developing PTSD.
  • Subgroups of interest include:
    • Demographic groups (defined by age, ethnic and racial groups, and sex)
    • Populations with psychiatric comorbidities
    • Populations with different personal risks of developing PTSD


  • Psychological interventions including:
    • Trauma-focused CBT
    • Cognitive restructuring and cognitive processing therapy
    • Exposure-based therapies
    • Coping skills therapy (including stress inoculation therapy)
    • Psychological first aid
    • Psychoeducation
    • Normalization
    • EMDR
    • Psychological debriefing
    • CISD
    • CISM
  • Pharmacological interventions including:
    • SSRIs: citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline
    • Serotonin–norepinephrine reuptake inhibitors (SNRIs: duloxetine, desvenlafaxine, and venlafaxine)
    • Other second-generation antidepressants (bupropion, mirtazapine, nefazodone, and trazodone)
    • Tricyclic antidepressants (imipramine, amitriptyline, and desipramine)
    • Monoamine oxidase inhibitors (phenelzine, isocarboxazid, selegiline, and tranylcypromine)
    • Alpha-blockers (prazosin)
    • Beta-blockers (propranolol)
    • Benzodiazepines (alprazolam, diazepam, lorazepam, clonazepam, and temazepam)
    • Anticonvulsants/mood stabilizers (topiramate, tiagabine, lamotrigine, carbamazepine, divalproex, and gabapentin)
    • Nonbenzodiazepine sedative/hypnotics (zolpidem, eszopiclone, rozerem, and zaleplon)
    • Atypical antipsychotics (olanzapine and risperidone)
    • Narcotic medication (morphine)
    • Steroids (hydrocortisone)
    • Opioid antagonists (naltrexone)
  • Emerging interventions
    • CAM (e.g., dietary supplements, yoga, guided imagery)


  • Psychological treatments (listed above) with one another
  • Pharmacological treatments (listed above) with one another
  • Psychological treatments with pharmacological treatments (listed above)
  • Pharmacological treatments with placebo
  • Psychological treatments with waiting list assignment, usual care, or no intervention


  • Final outcomesa
    • Incidence of PTSD
    • Incidence and severity of symptoms: assessor-rated or self-rated symptoms (e.g., sleep disturbance, anxiety)
    • Incidence and severity of comorbid conditions (e.g., depression, anxiety disorders, substance use, abuse, or dependence)
    • Quality of interpersonal or social functioning
    • Quality of life
    • Return to work or duty, or ability to work
    • Incidence of self-injurious or suicidal thoughts, attempts, or behaviors (including suicide)
    • Incidence of aggressive or homicidal thoughts, attempts, or behaviors (including homicide)
    • Resilience
    • Perceived utility
  • Adverse effects of intervention(s)
    • Adverse effects (e.g., worsening of anxiety or agitation, increased distress, headaches, gastrointestinal effects, effects on blood pressure, heart rate, sexual side effects, sedation or insomnia, treatment-associated hypomania or mania, medication dependence or misuse)
    • Dropout rate (overall dropout rate, dropout because of adverse effects, dropout because of lack of efficacy)


  • Intervention must be administered any time ranging from immediately to 3 months after exposure to a traumatic event
  • No limit for duration of followup


  • Any setting

a At least one PTSD-related outcome has to be addressed for a study to be eligible.

Analytic Framework

Figure 1 depicts the analytic framework for the comparative effectiveness of psychological and pharmacological interventions to prevent PTSD in adults. The KQs are displayed within the context of the population, intervention, comparator, outcome, timing, and setting described in the previous section. Beginning with a population of adults exposed to one or more traumatic events, the figure illustrates the absolute and comparative effects of early preventive interventions on incidence of PTSD or health outcomes, including incidence and severity of trauma-related symptoms, incidence and severity of comorbid conditions, quality of life, quality of interpersonal or social functioning, ability to return to work or military duty, incidence of self-injuries, suicidal thoughts, attempts, and behaviors, and incidence of aggressive or homicidal thoughts, attempts, and behaviors (KQ 1). Timing of an intervention as a potential mediator of these interventions is explored in KQ 2. Type of traumatic exposure and characteristics of subgroups as potential moderators of these interventions are explored in KQ 3. Subgroups within the overall population will be identified based on age, sex, race, and ethnicity, psychiatric comorbidities, and personal risk of PTSD.

KQ 4 addresses the absolute and comparative risks of harms and adverse events from these interventions.

Figure 1

Abbreviations: KQ = key question; PTSD = post-traumatic stress disorder


A. Criteria for Inclusion/Exclusion of Studies in the Review.

Table 3 presents the inclusion/exclusion criteria for this review. We do not repeat all of the PICOTS information related to the inclusion/exclusion criteria; Table 3 supplements the information outlined above in the PICOTS.

Table 3. Inclusion/exclusion criteria
Category Criteria
Inclusion Exclusion
a Due to limited time and resources, we will only include studies published in English.

Abbreviations: KQ = key question; PICOTS = populations, interventions, comparators, outcomes, timing, and setting; PTSD = post-traumatic stress disorder; TEP = Technical Expert Panel.
Population Adults exposed to psychological trauma, as defined above in the PICOTS
Geography No limits
Time period 1980 to present; searches to be updated after draft report goes out for peer review
Study duration No limits
Settings As defined above in the PICOTS
Interventions Early interventions (any time ranging from immediately to 3 months after exposure) to prevent PTSD, as defined above in the PICOTS
Control interventions Early interventions (any time ranging from immediately to 3 months after exposure) to prevent PTSD, as defined above in the PICOTS
Outcomes As listed above under the PICOTS
Publication language English All other languagesa
Admissible evidence (study design and other criteria) Original research
For KQs 1–4, eligible study designs include:
  • Randomized controlled trials.
  • Prospective controlled cohort studies

For KQs 2–4 when outcomes of interest are focused on harms, additional eligible study designs are:

  • Retrospective controlled cohort studies
  • Case control studies
  • Case series
  • Case reports
  • Systematic reviews and meta-analyses
  • Nonsystematic reviews
  • Editorials
  • Letters to the editor
  • Studies rated high risk of bias during quality assessment
  • Studies with historical, rather than concurrent, control groups
  • Pre-post studies without a separate control group

B. Searching for the Evidence: Literature Search Strategies for Identification of Relevant Studies To Answer the Key Questions

We will systematically search, review, and analyze the scientific evidence for each KQ. We will take the following steps to perform the literature search.

  1. To identify articles relevant to each KQ, we will begin with a focused MEDLINE® search using a variety of terms, medical subject headings (MeSH®), and major headings and limiting the search to English-language and human-only studies. Relevant terms are listed in Table 4. We will also search the Cochrane Library, the Cochrane Central Trials Registry, the Published International Literature on Traumatic Stress database, the Cumulative Index to Nursing and Allied Health Literature (CINAHL®) database, PsycINFO®, the International Pharmaceutical Abstracts database, EMBASE®, and Web of Science® by using analogous search terms. We will conduct quality checks to ensure that known studies (i.e., studies included in the previous review on treatment of adult PTSD and those identified during topic nomination and refinement) are identified by the search. If they are not, we will revise and rerun our searches.
  2. We will search the literature published in 1980 and later. We selected this 1980 search date based on the introduction/definition of PTSD as a clinical entity and based on the earliest publication date of relevant studies found in previous systematic reviews and expert opinion about when the earliest literature on this topic was published.
  3. We will search the “gray literature” for unpublished studies relevant to this review and will include studies that meet all the inclusion criteria and contain enough methodological information to assess internal validity/quality. Sources of gray literature include ClinicalTrials.gov, the U.S. Food and Drug Administration Web site, and dossiers prepared by pharmaceutical companies for pharmacotherapies of interest. AHRQ’s Scientific Resource Center will manage the process of submitting requests for scientific information packets, which contain information about pharmacotherapies of interest from relevant drug manufacturers.
  4. We will review our search strategy with the Technical Expert Panel (TEP) and supplement it as needed according to their recommendations. In addition, to attempt to avoid retrieval bias, we will manually search the reference lists of landmark studies and background articles on this topic to look for any relevant citations that electronic searches might have missed.
  5. We will also conduct an updated literature search (of the same databases searched initially) concurrent with the peer review process. We will investigate any literature the peer reviewers or the public suggest and, if appropriate, will incorporate them into the final review. Appropriateness will be determined by the same methods described above.
Table 4. Proposed PubMed literature search terms
Population “Traumatizing”[tiab] OR “Traumatising”[tiab] OR “Trauma”[tiab] OR “Traumatic”[tiab] OR “Traumas”[tiab] OR “Traumatization”[tiab] OR “Traumatisation”[tiab] OR “Traumatized”[tiab] OR “Traumatised”[tiab] OR "peritraumatic"[tiab] OR "Stress Disorders, Traumatic"[Mesh] OR "PTSD"[tiab] OR "post-traumatic stress disorders"[tiab] OR "post-traumatic stress disorder"[tiab] OR "posttraumatic stress disorders"[tiab] OR "posttraumatic stress disorder"[tiab] OR "Social Problems/psychology"[Mesh] OR "Life Change Events"[Mesh] OR "Stress, Psychological"[Mesh] OR "Wounds and Injuries/psychology"[Mesh] OR "Disasters"[Mesh] OR "survival/psychology"[Mesh]
Interventions Psychological intervention terms:
"Psychotherapy"[Mesh] OR "Complementary Therapies"[Mesh] OR "Therapeutics/psychology"[Mesh] OR "Adaptation, Psychological"[Mesh] OR "Mental Health Services"[Mesh]OR "prevention and control" [Subheading] OR "prevention"[tiab] OR "prevent"[tiab] OR "preventive"[tiab] OR "preventative"[tiab] OR "early intervention"[tiab] OR "Emergency Treatment/psychology"[Mesh] OR "Crisis Intervention"[Mesh] OR "Resilience, Psychological"[Mesh] OR "Preventive Health Services"[MeSH] OR "Preventive Medicine"[Mesh] OR "immediate treatment"[tiab]Pharmacologic intervention terms:
"Anesthetics, Dissociative"[Pharmacological Action] OR "Opiate Alkaloids"[Mesh] OR "Benzodiazepines"[MeSH] OR "Tranquilizing Agents"[Pharmacological Action] OR "Antipsychotic Agents"[Pharmacological Action] OR "Adrenergic Agents"[Pharmacological Action] OR "Anticonvulsants"[Pharmacological Action] OR "Monoamine Oxidase Inhibitors"[Pharmacological Action] OR "Antidepressive Agents"[Pharmacological Action] OR "Psychotropic Drugs"[Mesh]
Limits Humans;
All Adults: 19+ years

C. Data Abstraction and Data Management

Two trained research team members will independently review all titles and abstracts identified through searches for eligibility against our inclusion/exclusion criteria. Studies marked for possible inclusion by either reviewer will undergo a full-text review. For studies without adequate information to determine inclusion or exclusion, we will retrieve the full text and then make the determination. All results will be tracked in an EndNote® bibliographic database (Thomson Reuters, New York, NY).

We will retrieve and review the full text of all titles included during the title/abstract review phase. Two trained team members will independently review each full-text article for inclusion or exclusion based on the eligibility criteria described above. If both reviewers agree that a study does not meet the eligibility criteria, the study will be excluded. If the reviewers disagree, conflicts will be resolved by discussion and consensus or by consulting a third member of the review team. As described above, all results will be tracked in an EndNote database. We will record the reason why each excluded publication did not satisfy the eligibility criteria so that we can later compile a comprehensive list of such studies.

For studies that meet our inclusion criteria, we will abstract important information into evidence tables. We will design data abstraction forms to gather pertinent information from each article, including characteristics of study populations, settings, interventions, comparators, study designs, methods, and results. Trained reviewers will extract the relevant data from each included article into the evidence tables. A second member of the team will review all data abstractions for completeness and accuracy.

D. Assessment of the Risk of Bias of Individual Studies

To assess the risk of bias (internal validity) of studies, we will use predefined criteria based on guidance provided by AHRQ44 and the University of York Centre for Reviews and Dissemination.45 In general terms, results of a study with low risk of bias are considered to be valid. A study with medium risk of bias is susceptible to some bias but probably not sufficient enough to invalidate its results. A study with high risk of bias has significant methodological flaws (e.g., stemming from serious errors in design or analysis) that may invalidate its results. We will consider the risk of bias for each relevant outcome of a study.

Two independent reviewers will assess the risk of bias for each study. Disagreements between the two reviewers will be resolved by discussion and consensus or by consulting a third member of the team. We will rate studies that meet all criteria as having “low risk of bias.” “Medium risk of bias” ratings will be given to studies that presumably fulfill all quality criteria but do not report their methods sufficiently to answer all of our questions. We will give a “high risk of bias” rating to studies that have a fatal flaw (defined as a methodological shortcoming that leads to a very high risk of bias) in one or more categories and will exclude them from our analyses.

E. Data Synthesis

If we find three or more similar studies for a comparison of interest, we will consider quantitative analysis (i.e., meta-analysis) of the data from those studies. We will also consider conducting mixed treatment comparisons meta-analysis using Bayesian methods to compare the pharmacological interventions with each other if we identify a sufficient number of studies with a common comparator (e.g., placebo). For all analyses, we will use random-effects models to estimate pooled or comparative effects. To determine whether quantitative analyses are appropriate, we will assess the clinical and methodological heterogeneity of the studies under consideration following established guidance.46 We will do this by qualitatively assessing the PICOTS of the included studies, looking for similarities and differences. If we conduct quantitative syntheses (i.e., meta-analyses), we will assess statistical heterogeneity in effects between studies by calculating the chi-squared statistic and the I2 statistic (the proportion of variation in study estimates due to heterogeneity). The importance of the observed value of I2 depends on the magnitude and direction of effects and on the strength of evidence for heterogeneity (e.g., p-value from the chi-squared test, or a confidence interval for I2). If we include any meta-analyses with considerable statistical heterogeneity in this report, we will provide an explanation for doing so, considering the magnitude and direction of effects. We will also examine potential sources of heterogeneity by using sensitivity analysis or subgroup analyses. We plan to stratify analyses and/or perform subgroup analyses when possible and appropriate to examine clinical heterogeneity. Planned stratifications or categories for subgroup analyses include the subgroups listed in the analytic framework and geographic location of studies. When quantitative analyses are not appropriate (e.g., due to heterogeneity, insufficient numbers of similar studies, or insufficiency or variation in outcome reporting), we will synthesize the data qualitatively.

F. Grading the Evidence for Each Key Question

We will grade the strength of evidence based on the guidance established for the Evidence-based Practice Center Program.47 Developed to grade the overall strength of a body of evidence, this approach incorporates four key domains: risk of bias (includes study design and aggregate quality), consistency, directness, and precision of the evidence. It also considers other optional domains that may be relevant for some scenarios, such as a dose-response association, plausible confounding that would decrease the observed effect, strength of association (magnitude of effect), and publication bias.

Table 5 describes the grades of evidence that can be assigned. Grades reflect the strength of the body of evidence to answer KQs on the comparative effectiveness, efficacy, and harms of the interventions included in this review. Two reviewers will assess each domain for each key outcome, and differences will be resolved by consensus. We will grade the strength of evidence for the outcomes deemed to be of greatest importance to decisionmakers and those most commonly reported in the literature. We expect these to include PTSD symptom reduction, quality of life, disability/functional impairment, and adverse events.

Table 5. Definitions of the grades of overall strength of evidence47
Grade Definition
High High confidence that the evidence reflects the true effect. Further research is very unlikely to change our confidence in the estimate of effect.
Moderate Moderate confidence that the evidence reflects the true effect. Further research may change our confidence in the estimate of the effect and may change the estimate.
Low Low confidence that the evidence reflects the true effect. Further research is likely to change our confidence in the estimate of the effect and is likely to change the estimate.
Insufficient Evidence either is unavailable or does not permit estimation of an effect.

G. Assessing Applicability

We will assess applicability of the evidence following guidance from the Methods Guide for Effectiveness and Comparative Effectiveness Reviews.44 We will use the PICOTS framework to explore factors that affect applicability. Some factors identified a priori that may limit the applicability of evidence include the following: age of enrolled populations; sex of enrolled populations (e.g., few women may be enrolled in the studies); race/ethnicity of enrolled populations; few studies enrolling subjects with exposure to certain types of trauma; or few studies distinguishing/reporting the type of traumatic exposure for a heterogeneous population.


  1. American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. Washington, DC: American Psychiatric Publishing, Inc.; 2000.
  2. Resnick HS, Kilpatrick DG, Dansky BS, et al. Prevalence of civilian trauma and posttraumatic stress disorder in a representative national sample of women. J Consult Clin Psychol 1993 Dec;61(6):984-91. PMID: 8113499.
  3. Kessler RC, Sonnega A, Bromet E, et al. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1995 Dec;52(12):1048-60. PMID: 7492257.
  4. Norris F, Sloane LB. The epidemiology of trauma and PTSD. In: Friedman MJ, Keane TM, Resick PA, eds. Handbook of PTSD: Science and practice. New York, NY: Guilford Press; 2007. p. 78-98.
  5. Vrana S, Lauterbach D. Prevalence of traumatic events and post-traumatic psychological symptoms in a nonclinical sample of college students. J Trauma Stress 1994 Apr;7(2):289-302. PMID: 8012748.
  6. Breslau N, Davis GC, Andreski P, et al. Traumatic events and posttraumatic stress disorder in an urban population of young adults. Arch Gen Psychiatry 1991 Mar;48(3):216-22. PMID: 1996917.
  7. Norris FH. Epidemiology of trauma: frequency and impact of different potentially traumatic events on different demographic groups. J Consult Clin Psychol 1992 Jun;60(3):409-18. PMID: 1619095.
  8. Brewin CR, Dalgleish T, Joseph S. A dual representation theory of posttraumatic stress disorder. Psychol Rev 1996 Oct;103(4):670-86. PMID: 8888651.
  9. Ozer EJ, Best SR, Lipsey TL, et al. Predictors of posttraumatic stress disorder and symptoms in adults: a meta-analysis. Psychol Bull 2003 Jan;129(1):52-73. PMID: 12555794.
  10. Bryant RA, Harvey AG, Guthrie RM, et al. A prospective study of psychophysiological arousal, acute stress disorder, and posttraumatic stress disorder. J Abnorm Psychol 2000 May;109(2):341-4. PMID: 10895573.
  11. McCleery JM, Harvey AG. Integration of psychological and biological approaches to trauma memory: implications for pharmacological prevention of PTSD. J Trauma Stress 2004 Dec;17(6):485-96. PMID: 15730067.
  12. Pitman RK. Post-traumatic stress disorder, hormones, and memory. Biol Psychiatry 1989 Jul;26(3):221-3. PMID: 2545287.
  13. Bryant RA. Early predictors of posttraumatic stress disorder. Biol Psychiatry 2003 May 1;53(9):789-95. PMID: 12725971.
  14. Mitchell JT. When disaster strikes...the critical incident stress debriefing process. JEMS 1983 Jan;8(1):36-9. PMID: 10258348.
  15. Barboza K. Critical incident stress debriefing (CISD): efficacy in question. N School Psychol Bull 2005;3(2):49-70.
  16. Boudreaux ED, McCabe B. Emergency psychiatry: critical incident stress management: I. Interventions and effectiveness. Psychiatr Serv 2000 Sep;51(9):1095-7. PMID: 10970908.
  17. Gray MJ, Maguen S, Litz BT. Acute psychological impact of disaster and large-scale tauma: limitations of traditional interventions and future practice recommendations. Prehosp Disaster Med 2004 Jan-Mar;19(1):64-72. PMID: 15453161.
  18. Mitchell JT, Everly GS, Mitchell DJ. The hidden victims of disasters and vehicular accidents: the problem and recommended solutions. In: Hickling EJ and Blanchard EB, eds. The international handbook of road traffic accidents and psychological trauma: current understanding, treatment and law. Vol. 30. New York, NY: Elsevier Science; 1999. p. 141-53.
  19. van Emmerik AA, Kamphuis JH, Hulsbosch AM, et al. Single session debriefing after psychological trauma: a meta-analysis. Lancet 2002 Sep 7;360(9335):766-71. PMID: 12241834.
  20. Litz BT, Gray MJ, Bryant RA, et al. Early intervention for trauma: current status and future directions. Clin Psychol Sci Pract 2002;9(2):112-34.
  21. Rose S, Bisson J, Churchill R, et al. Psychological debriefing for preventing post traumatic stress disorder (PTSD). Cochrane Database Syst Rev 2002;(2):CD000560. PMID: 12076399.
  22. Ruzek JI, Brymer MJ, Jacobs AK, et al. Psychological first aid. J Ment Health Couns 2007;29(1):17-49.
  23. Brymer M, Jacobs A, Layne C, et al; National Child Traumatic Stress Network and National Center for PTSD. Psychological first aid: field operations guide. 2nd ed. Washington, DC: U.S. Department of Veterans Affairs; 2006. Available at www.ptsd.va.gov/professional/manuals/psych-first-aid.asp.
  24. Institute of Medicine. Treatment of PTSD: an assessment of the evidence. Washington, DC: National Academies Press; 2008. Available at www.iom.edu/Reports/2007/Treatment-of-PTSD-An-Assessment-of-The-Evidence.aspx.
  25. Foa EB, Keane TM, Friedman MJ and Cohen J eds. Effective treatments for PTSD: practice guidelines from the International Society for Traumatic Stress Studies 2nd ed. New York, NY: Guilford Press; 2009.
  26. Sones HM, Thorp SR, Raskind M. Prevention of posttraumatic stress disorder. Psychiatr Clin North Am 2011 Mar;34(1):79-94. PMID: 21333841.
  27. Wood DP, Murphy J, McLay R, et al. Cost effectiveness of virtual reality graded exposure therapy with physiological monitoring for the treatment of combat related post traumatic stress disorder. Stud Health Technol Inform 2009;144:223-9. PMID: 19592768.
  28. Friedman MJ. Post-traumatic stress disorder: The latest assessment and treatment strategies. 3rd ed. Kansas City, MO: Compact Clinicals; 2003.
  29. Southwick SM, Davis LL, Aikins DE, et al. Neurobiological alterations associated with PTSD. In: Friedman MJ, Keane TM and Resick PA, eds. Handbook of PTSD: science and practice. New York, NY: Guilford Press; 2007. p. 166-89.
  30. Pitman RK, Sanders KM, Zusman RM, et al. Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry 2002 Jan 15;51(2):189-92. PMID: 11822998.
  31. Stein MB, Kerridge C, Dimsdale JE, et al. Pharmacotherapy to prevent PTSD: results from a randomized controlled proof-of-concept trial in physically injured patients. J Trauma Stress 2007 Dec;20(6):923-32. PMID: 18157888.
  32. Hoge EA, Worthington JJ, Nagurney JT, et al. Effect of acute posttrauma propranolol on PTSD outcome and physiological responses during script-driven imagery. CNS Neurosci Ther 2012 Jan;18(1):21-7. PMID: 22070357.
  33. Reist C, Duffy JG, Fujimoto K, et al. beta-Adrenergic blockade and emotional memory in PTSD. Int J Neuropsychopharmacol 2001 Dec;4(4):377-83. PMID: 11806863.
  34. Bryant RA, Creamer M, O’Donnell M, et al. A study of the protective function of acute morphine administration on subsequent posttraumatic stress disorder. Biol Psychiatry 2009;65(5):438-40. PMID: 2009-02023-018.
  35. Holbrook TL, Galarneau MR, Dye JL, et al. Morphine use after combat injury in Iraq and post-traumatic stress disorder. N Engl J Med 2010 Jan;362(2):110-7. PMID: 20071700.
  36. Schelling G, Roozendaal B, De Quervain DJ. Can posttraumatic stress disorder be prevented with glucocorticoids? Ann N Y Acad Sci 2004 Dec;1032:158-66. PMID: 15677403.
  37. Schelling G, Briegel J, Roozendaal B, et al. The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder in survivors. Biol Psychiatry 2001 Dec 15;50(12):978-85. PMID: 11750894.
  38. Raskind MA. Pharmacologic treatment of PTSD. In: Shiromani PJ, Keane TM and LeDoux JE, eds. Post-traumatic stress disorder: basic science and clinical practice. New York, NY: Humana Press; 2009. p. 337-61.
  39. Friedman MJ, Marmar CR, Baker DG, et al. Randomized, double-blind comparison of sertraline and placebo for posttraumatic stress disorder in a Department of Veterans Affairs setting. J Clin Psychiatry 2007 May;68(5):711-20. PMID: 17503980.
  40. Matar MA, Cohen H, Kaplan Z, et al. The effect of early poststressor intervention with sertraline on behavioral responses in an animal model of post-traumatic stress disorder. Neuropsychopharmacology 2006 Dec;31(12):2610-8. PMID: 16794565.
  41. National Institutes of Health. CAM basics: what is complementary and alternative medicine? NIH Publication No. D347. Updated July 2011. Available at www.nccam.nih.gov/sites/nccam.nih.gov/files/D347.pdf.
  42. Forbes D, Creamer M, Bisson JI, et al. A guide to guidelines for the treatment of PTSD and related conditions. J Trauma Stress 2010 Oct;23(5):537-52. PMID: 20839310.
  43. Ursano RJ, Bell C, Eth S, et al; Work Group on ASD and PTSD; Steering Committee on Practice Guidelines. Practice guideline for the treatment of patients with acute stress disorder and posttraumatic stress disorder. Am J Psychiatry 2004;161(11 Suppl):3-31. PMID: 15617511.
  44. Atkins D, Chang S, Gartlehner G, et al. Assessing the applicability of studies when comparing medical interventions. In: Methods guide for effectiveness and comparative effectiveness reviews. Rockville, MD: Agency for Healthcare Research and Quality; January 2011. Available at www.effectivehealthcare.ahrq.gov/tasks/sites/ehc/assets/File/Methods_Guide_Atkins.pdf
  45. Center for Reviews and Dissemination, University of York. Systematic reviews: CRD's guidance for undertaking reviews in health care. January 2009. Available at www.york.ac.uk/inst/crd/pdf/Systematic_Reviews.pdf.
  46. West SL, Gartlehner G, Mansfield AJ, et al. Comparative Effectiveness Review Methods: Clinical Heterogeneity. Methods Research Report (Prepared by RTI International–University of North Carolina Evidence-based Practice Center under Contract No. 290-2007-10056-I). Rockville, MD: Agency for Healthcare Research and Quality; September 2010. AHRQ Publication No. 11-EHC070-EF. Available at www.ncbi.nlm.nih.gov/books/NBK53310/pdf/TOC.pdf
  47. Owens DK, Lohr KN, Atkins D, et al. AHRQ series paper 5: grading the strength of a body of evidence when comparing medical interventions—Agency for Healthcare Research and Quality and the Effective Health-Care Program. J Clin Epidemiol 2010 May;63(5):513-23. PMID: 19595577.
  48. Substance Abuse and Mental Health Services Administration Web site. Resilience and Stress Management Resource Collection. Version 1.0. Resilience. Available at www.samhsa.gov/dtac/dbhis/dbhis_stress/resilience.htm. Accessed January 31, 2012.
  49. National Center for PTSD Web site. Professional Section. Clinician-Administered PTSD Scale (CAPS). Reviewed/Updated December 20, 2011. Available at www.ptsd.va.gov/PTSD//professional/pages/assessments/caps.asp.
  50. Davidson J. DTS™: Davidson Trauma Scale. North Tonawanda, NY: Multi-Health Systems, Inc.; 2004. Available at www.mhs.com/product.aspx?gr=cli&prod=dts&id=overview#scales.
  51. National Center for PTSD Web site. Professional Section. Davidson Trauma Scale (DTS). Available at www.ptsd.va.gov/professional/pages/assessments/dts.asp.
  52. Horowitz M, Wilner N, Alvarez W. Impact of event scale: a measure of subject stress. Psychosom Med 1979;41(3):209-18. PMID: 472086.
  53. National Center for PTSD Web site. Professional Section. Impact of Events Scale–Revised (IES-R). Available at www.ptsd.va.gov/professional/pages/assessments/ies-r.asp.
  54. National Center for PTSD Web site. Professional Section. Modified PTSD Symptom Scale (MPSS-SR). Available at www.ptsd.va.gov/professional/pages/assessments/mpss-sr.asp.
  55. National Center for PTSD Web site. Professional Section. Penn Inventory for Posttraumatic Stress Disorder (Penn Inventory). Available at www.ptsd.va.gov/professional/pages/assessments/penn-inventory-ptsd.asp.
  56. National Center for PTSD. Professional Section. PTSD Checklist (PCL). Washington, DC: U.S. Department of Veterans Affairs; 2010. Available at www.ptsd.va.gov/professional/pages/assessments/ptsd-checklist.asp.
  57. Watson CG, Juba MP, Anderson PE. The PTSD interview: rationale, description, reliability, and concurrent validity of a DSM-III-based technique. J Clin Psychol 1991;47:179-88. PMID: 2030122.
  58. National Center for PTSD. Professional Section. PTSD Symptom Scale–Interview (PSS-I). Available at www.ptsd.va.gov/professional/pages/assessments/pss-i.asp.
  59. Foa EB, Riggs DS, Dancu C, et al. Reliability and validity of a brief instrument for assessing post-traumatic stress disorder. J Trauma Stress 1993;6(4):459-73.
  60. National Center for PTSD Web site. Professional Section. Structured Interview for PTSD (SI-PTSD). Available at www.ptsd.va.gov/professional/pages/assessments/si-ptsd.asp.
  61. National Center for PTSD Web site. Professional Section. Structured Clinical Interview for the DSM-IV Axis I Disorders (SCID PTSD Module). Available at www.ptsd.va.gov/professional/pages/assessments/scid-ptsd-module.asp.

Definition of Terms

Absolute effectiveness: the effectiveness of an intervention relative to a nonactive control group, that is, either assigned to a waitlist group or receiving a placebo intervention

Absolute risk of harms: an intervention’s risk of harms relative to a nonactive control group, that is, either assigned to a waitlist group or receiving a placebo intervention

Intensity: the length and number of treatment sessions for a psychological intervention; the equivalent of dosage for pharmacological interventions

Perceived utility: the extent to which recipients of an intervention subjectively find value in and/or express satisfaction with the intervention

Resilience: the ability to cope with adversity, such as traumatic exposures, and adapt to challenges or change48

Summary of Protocol Amendments

Date Section Original Protocol Revised Protocol Rationale



The previous revision made to Figure 1 on 9/26/2012 did not make it clear that KQ 3 addressed the effectiveness of interventions among subgroups, rather than the entire target population of the review.

The text “( KQ 3)” was moved to follow “Subgroups” immediately in the “Population at risk…” box was revised as follows: “Subgroups (KQ 3)”.

The team decided that the subgroup focus of KQ 3 could be made clearer in the Analytic Framework with this revision.



The term “absolute effectiveness” was used in the KQs.

“Absolute effectiveness” has been replaced by “efficacy”.

The team decided after submitting the draft report that “efficacy” was a more readily understood term than “absolute effectiveness”.



In the description of PICOTS, the description of eligible intervention types (i.e., psychological, pharmacological, and emerging) did not take into account other interventions not specifically named.

The following sub-bullets have been added below each eligible intervention type: 1) “Other clearly defined psychological interventions” under “Psychological interventions”; 2) “Other clearly defined pharmacological interventions” under “Pharmacological interventions”; and 3) “Other clearly defined emerging interventions” under “Emerging Interventions”.

The team had originally planned to consider interventions not specifically named in the PICOTS for potential inclusion, but this was not made clear in the original version of the list.



In Figure 1, it was unclear which KQ the subgroups listed in the “Population at risk…” box pertain to.

The “Population at risk…” box was revised as follows: “Population at risk: Adults exposed to psychological trauma (KQ 3)”.

This revision was necessary to respond to a peer reviewer’s comment suggesting that we clarify that the subgroups listed in the “Population at risk…” box of Figure 1 are the focus of KQ 3.



In Figure 1, there was a typographical error in the “Timing, intensity…” box: the word “Intervention” should be entirely lowercase.

The typographical error was corrected.

This error was unintentional.



No description of ineligible intervention types was provided in Table 3, which presents the CER’s eligibility criteria.

The following exclusion criterion has been added to the “Interventions” and “Control Interventions” rows in Table 3: “Undefined or non-clinical interventions”.

The team had originally planned to consider only clearly-defined, clinical interventions, but this was not made clear in the PICOTS or in the original version of Table 3.



The term “absolute effectiveness” was included under “Summary of Terms”.

“Absolute effectiveness” has been replaced by “efficacy”.

The team decided after submitting the draft report that “efficacy” was a more readily understood term than “absolute effectiveness”.



The original description of EMDR was outdated.

The last paragraph of Section Psychological Debriefing, CISD, and CISM has been revised as follows:

EMDR combines imaginal exposure with the concurrent induction of saccadic eye movements that are believed to help reprogram brain function so that emotional impact of trauma can be resolved. In EMDR, the patient is asked to hold the distressing image in mind, along with the associated negative cognition and bodily sensations, while engaging in saccadic eye movements. After approximately 20 seconds, the therapist asks the patient to “blank it out,” take a deep breath, and note any changes occurring in the image, sensations, thoughts or emotions. The process is repeated until desensitization has occurred (i.e., patient reports little or no distress on Subjective Units of Distress Scales), at which time the patient is asked to hold in mind a previously identified positive cognition, while engaging in saccadic eye movements, and rating the validity of this cognition while going through the procedure as outlined above. The saccadic eye movements were initially theorized to both interfere with working memory and elicit an orienting response, which lower emotional arousal so that the trauma can be resolved. The eye movements, or other alternative parallel stimulation, have since been found in dismantling studies to be unnecessary in achieving desensitization. Although earlier versions of EMDR consisted of 1 to 3 sessions, current standards consist of 8 to 12 90-minute weekly sessions.24, 28

Investigators conducting a concurrent CER of treatments for adult PTSD used the same original description of EMDR in their project protocol and received suggestions during their public comment period to update its description. Following this guidance, the EMDR description is revised for this project’s protocol to be consistent with concurrent CER of treatments for adult PTSD.



In Table 2, temazepam was missing from the list of benzodiazepines studied for the prevention or treatment of PTSD.

Temazepam has been added to Table 2.

Temazepam is one of the pharmacological interventions of interest in this project’s PICOTS, but was unintentionally omitted from Section I’s Table 2.



In Table 2, the SSRI escitalopram was unintentionally listed a second time as “citalopram”.

“Citalopram” has been deleted from the list of SSRIs in Table 2.

This was an unintentional duplication.



One of the drug classes listed in the description of PICOTS was “anticonvulsants/mood stabilizers”.

The drug class is now listed as

One member of our Technical Expert Panel suggested removing “mood stabilizers” from the title of this drug class.



In the description of PICOTS, escitalopram was unintentionally listed a second time as “citalopram” (see Amendment for Section I, Table 2).

“Citalopram” has been deleted from the PICOTS.

This was an unintentional duplication.



Analytic Framework’s list of outcomes was missing “resilience.”

Analytic Framework now includes “resilience” in its list of outcomes.

The team identified resilience as an outcome of interest early in the project’s timeline, but resilience was unintentionally omitted from the Analytic Framework.

Review of KQs

For all EPC reviews, KQs are reviewed and refined as needed by the EPC with input from Key Informants and the TEP to assure that the questions are specific and explicit about what information is being reviewed. In addition, for Comparative Effectiveness Reviews, the KQs are posted for public comment and finalized by the EPC after review of the comments.

Key Informants

Key Informants are the end-users of research, including patients and caregivers, practicing clinicians, relevant professional and consumer organizations, purchasers of health care, and others with experience in making health care decisions. Within the EPC program, the Key Informant role is to provide input into identifying the KQs for research that will inform health care decisions. The EPC solicits input from Key Informants when developing questions for systematic review or when identifying high-priority research gaps and needed new research. Key Informants are not involved in analyzing the evidence or writing the report and have not reviewed the report, except as given the opportunity to do so through the peer or public review mechanism.

Key Informants must disclose any financial conflicts of interest greater than $10,000 and any other relevant business or professional conflicts of interest. Because of their role as end-users, individuals are invited to serve as Key Informants, and those who present with potential conflicts may be retained. The Task Order Officer (TOO) and the EPC work to balance, manage, or mitigate any potential conflicts of interest identified.

Technical Experts

Technical Experts comprise a multidisciplinary group of clinical, content, and methodological experts who provide input in defining populations, interventions, comparisons, or outcomes as well as identifying particular studies or databases to search. They are selected to provide broad expertise and perspectives specific to the topic under development. Divergent and conflicted opinions are common and perceived as healthy scientific discourse that results in a thoughtful, relevant systematic review. Therefore, study questions, design, and/or methodological approaches do not necessarily represent the views of individual technical and content experts. Technical Experts provide information to the EPC to identify literature search strategies and recommend approaches to specific issues as requested by the EPC. Technical Experts do not perform analysis of any kind nor contribute to the writing of the report, and they have not reviewed the report, except as given the opportunity to do so through the public review mechanism.

Technical Experts must disclose any financial conflicts of interest greater than $10,000 and any other relevant business or professional conflicts of interest. Because of their unique clinical or content expertise, individuals are invited to serve as Technical Experts, and those who present with potential conflicts may be retained. The TOO and the EPC work to balance, manage, or mitigate any potential conflicts of interest identified.

Peer Reviewers

Peer Reviewers are invited to provide written comments on the draft report based on their clinical, content, or methodological expertise. Peer review comments on the preliminary draft of the report are considered by the EPC in preparation of the final draft of the report. Peer Reviewers do not participate in writing or editing of the final report or other products. The synthesis of the scientific literature presented in the final report does not necessarily represent the views of individual Reviewers. The dispositions of the peer review comments are documented and will, for Comparative Effectiveness Reviews and Technical Briefs, be published 3 months after the publication of the Evidence report.

Potential Reviewers must disclose any financial conflicts of interest greater than $10,000 and any other relevant business or professional conflicts of interest. Invited Peer Reviewers may not have any financial conflict of interest greater than $10,000. Peer Reviewers who disclose potential business or professional conflicts of interest may submit comments on draft reports through the public comment mechanism.

Evidence-based Practice Center Team Disclosures

With the exception of the following, the team had no interests to disclosure:

  • Lead Clinical Investigator’s Statement of Disclosure of Business and Professional Interest:
    • Member, Binge Eating Disorder Association Scientific Advisory Board
  • Co-Investigator A’s Statement of Disclosure of Business and Professional Interest:
    • Editorial Board for Medscape Psychiatry and Mental Health, a continuing medical education organization

Role of the Funder

This project was funded under Contract No. 290-2007-10056-I from the Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services. The TOO reviewed contract deliverables for adherence to contract requirements, including the objectivity and independence of the research process and the methodological quality of the report. The authors of this report are responsible for its content. Statements in the report should not be construed as endorsement by the Agency for Healthcare Research and Quality or the U.S. Department of Health and Human Services.

Appendix A. Post-traumatic stress disorder outcome measures

Outcome Measure Description

DSM = Diagnostic and Statistical Manual of Mental Disorders1

Clinician-Administered PTSD Scale (CAPS)24, 49
  • Gold standard for post-traumatic stress disorder (PTSD) assessment and diagnosis for military and civilian trauma survivors.
  • 30-item structured interview that corresponds to the DSM-IV criteria for PTSD.
  • Can be used to make a current or lifetime diagnosis of PTSD or to assess symptoms over the past week.
  • In addition to PTSD symptoms, CAPS assesses the impact of symptoms on social and occupational functioning, improvement in symptoms since a previous CAPS administration, overall response validity, overall PTSD severity, and frequency and intensity of five associated symptoms (guilt over acts, survivor guilt, gaps in awareness, depersonalization, and derealization).
  • Can be used to make a current or lifetime diagnosis of PTSD or to assess symptoms over the past week.
  • Administered in 45- to 60-minutes by trained (para)professionals.
Clinician-Administered PTSD Scale Part 2 (CAPS-2)49
  • Assesses 1-week symptom status.
Davidson Trauma Scale (DTS)50, 51
  • 17-item self-rating scale used to assess DSM-IV PTSD criteria (B–D).
  • Each item corresponds to a DSM-IV symptom of PTSD, and each symptom is rated in terms of frequency and severity.
  • Can be used to screen clients at initial evaluation, evaluate psychopathology in trauma victims, assess the effectiveness of treatment, and predict treatment success.
  • Scale covers the following types of trauma: accident, combat, sexual, criminal assault, natural disaster, torture, burns, loss of property, near-death experiences, and bereavement.
  • Administered in approximately 10 minutes.
Diagnostic Interview Schedule (DIS)24
  • Assesses DSM III-R/IV symptomatology and can be used for PTSD diagnosis.
  • Semistructured interview.
  • Requires patient to associate each symptom with a specific traumatic event.
  • Administered in 15 minutes by trained lay interviewers.
Impact of Events Scale (IES)52
  • 15-item self-reported measure used to assess the frequency with which experiences of “intrusions,” “avoidance,” and emotional numbing related to stressful events occurred in the last week.
  • A total distress score is calculated by summing all 15 item responses.
Impact of Events Scale–Revised (IES-R)53
  • 22-item self-report measure that assesses subjective distress caused by traumatic events.
  • Items correspond directly to 14 of the 17 DSM-IV symptoms of PTSD.
Los Angeles Symptom Checklist (LASC)24
  • 43-item self-report measure used to assess PTSD symptoms and associated features, including signs of distress and functional problems.
Minnesota Multiphasic Personality Inventory (MMPI), Keane PTSD Scale24
  • Self-report questionnaire.
  • Originally composed of 29 items, revised for MMPI-2 by deleting three repetitious items.
  • 46 MMPI items.
  • Norms available for different populations.
Mississippi Scale for Combat-related PTSD (M-PTSD)24
  • 35-item self-report questionnaire used to assess DSM-III combat-related PTSD and related features (depression, suicidality, and substance abuse).
  • Administered in 10 to 15 minutes.
Modified PTSD Symptom Scale (MPSS-SR)54
  • 17-item self-report measure that assesses the 17 DSM-III-R symptoms of PTSD.
  • This scale is a modification of the PTSD Symptom Scale.
  • The major modifications are that the items are not keyed to any particular traumatic event and that the MPSS-SR includes severity ratings in addition to the original measure’s frequency ratings for each item.
  • It can be used to make a preliminary determination of the diagnosis of PTSD using DSM-III-R criteria or frequency, severity, or total score cutoff scores.
  • It can be scored as a continuous measure of PTSD symptom severity.
Penn Inventory for Posttraumatic Stress Disorder24,55
  • 26-item self-report questionnaire primarily used with male patients, including accident victims, veterans, and general psychiatric patients.
  • It does not assess all of the 17 DSM symptoms of PTSD and includes items that are not directly related to DSM criteria (e.g., self-knowledge).
Posttraumatic Diagnostic Scale (PTDS)24
  • 17 questions, including a 12-item checklist of traumatic events used to assess DSM-IV PTSD criteria.
  • Assesses frequency of PTSD symptoms in the past month and self-ratings of impairment across nine areas of functioning.
  • Has been validated across several populations, including combat veterans and sexual and nonsexual assault survivors.
PTSD Checklist (PCL)56
  • 17-item self-report measure of the 17 DSM-IV symptoms of PTSD.
  • The PCL has been used to screen individuals for PTSD, diagnose PTSD, and monitor symptom change during and after treatment.
  • There are three versions of the PCL: PCL-M (military), PCL-C (civilian), and PCL-S (specific).
  • Administered in 5 to 10 minutes.
PTSD Interview
  • Structured clinical interview.
  • Patients given a copy of scale to read along with interviewer and asked to give subjective ratings for each symptom.
  • Administered by trained subprofessionals.
PTSD Symptom Scale–Interview (PSS-I)58
  • 17-item semistructured interview that assesses the presence and severity of DSM-IV PTSD symptoms related to a single identified traumatic event in individuals with a known trauma history.
  • Each item is assessed with a single brief question.
  • Interviewees are asked about symptoms they have experienced in the past 2 weeks.
  • Administered in approximately 20 minutes.
PTSD Symptom Scale- Self-report Version (PSS-SR)59
  • 17-item scale used to diagnose PTSD according to DSM-III-R criteria .
  • Assesses the severity of PTSD symptoms (consists of the same 17 items as the PSS-I).
Structured Interview for PTSD (SI-PTSD or SIP)60
  • Assesses the 17 PTSD symptoms, as well as survival and behavioral guilt.
  • For each item, the interviewer assigns a severity rating that reflects both frequency and intensity.
  • Item responses can be used to make a determination about whether a client's symptoms meet DSM criteria B, C, and D for PTSD.
  • Administered in 20 to 30 minutes.
Structured Clinical Interview (SCID) PTSD Module24, 61
  • Semistructured interview used to assess the prevalence, absence, and subthreshold presence of PTSD across trauma populations.
  • It consists of separate modules corresponding to categories of diagnoses.
  • Administered in 25 minutes.
Symptom Checklist-90–Revised (SCL-90-R)24
  • 90-item self-report questionnaire used to assess a broad range of psychological problems, symptoms of psychopathology, patient progress, and treatment outcomes.
  • Administered in 12 to 15 minutes.

Project Timeline

Interventions for the Prevention of Posttraumatic Stress Disorder (PTSD) in Adults After Exposure to Psychological Trauma

Jan 4, 2012
Topic Initiated
Jun 6, 2012
Research Protocol Archived
Apr 2, 2013
Page last reviewed December 2019
Page originally created November 2017

Internet Citation: Research Protocol: Interventions for the Prevention of Post-traumatic Stress Disorder in Adults After Exposure to Psychological Trauma. Content last reviewed December 2019. Effective Health Care Program, Agency for Healthcare Research and Quality, Rockville, MD.

Select to copy citation