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Early Intervention May Prevent the Development of Posttraumatic Stress Disorder: A Randomized Pilot Civilian Study with Modified Prolonged Exposure Barbara Olasov Rothbaum, Megan C. Kearns, Matthew Price, Emily Malcoun, Michael Davis, Kerry J. Ressler, Delia Lang, and Debra Houry

Background: Posttraumatic stress disorder (PTSD) is a major public health concern with long-term sequelae. There are no accepted interventions delivered in the immediate aftermath of trauma. This study tested an early intervention aimed at modifying the memory to prevent the development of PTSD before memory consolidation.

Methods: Patients (n � 137) were randomly assigned to receive three sessions of an early intervention beginning in the emergency department compared with an assessment only control group. Posttraumatic stress reactions (PTSR) were assessed at 4 and 12 weeks postinjury and depression at baseline and week 4. The intervention consisted of modified prolonged exposure including imaginal exposure to the trauma memory, processing of traumatic material, and in vivo and imaginal exposure homework.

Results: Patients were assessed an average of 11.79 hours posttrauma. Intervention participants reported significantly lower PTSR than the assessment group at 4 weeks postinjury, p � .01, and at 12 weeks postinjury, p � .05, and significantly lower depressive symptoms at week 4 than the assessment group, p � .05. In a subgroup analysis, the intervention was the most effective at reducing PTSD in rape victims at week 4 (p � .004) and week 12 (p � .05).

Conclusions: These findings suggest that the modified prolonged exposure intervention initiated within hours of the trauma in the emergency department is successful at reducing PTSR and depression symptoms 1 and 3 months after trauma exposure and is safe and

feasible. This is the first behavioral intervention delivered immediately posttrauma that has been shown to be effective at reducing PTSR.

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Key Words: Acute stress disorder, early intervention, memory con- solidation, prolonged exposure, PTSD, secondary prevention

A pproximately 60.7% of men and 51.2% of women are esti- mated to experience a traumatic event in their lifetimes (1). While a majority of individuals will experience symptoms of

osttraumatic stress in the immediate aftermath of a trauma, pro- pective studies indicate that these reactions typically extinguish ver time (2). However, a subset of individuals will develop post-

raumatic stress disorder (PTSD). The majority of prevention re- earch has focused on psychological debriefing (PD). Psychological ebriefing typically includes seven phases that incorporate oppor-

unities for survivors to talk about their trauma reactions and re- eive support and psychoeducation (3). Unfortunately, controlled esearch on PD has suggested that it is either ineffective or even otentially harmful, which has led experts to discourage its use as a revention approach for PTSD (4). With no clear candidate currently vailable for early intervention, research identifying short-term, ost-effective, and easily disseminable interventions is extremely

mportant, especially given the significant public health impact of TSD.

From the Department of Psychiatry and Behavioral Sciences (BOR, MCK, EM, MD, KJR, DH); Department of Emergency Medicine (DH); Emory Univer- sity School of Medicine, Atlanta, Georgia; Department of Psychiatry and Behavioral Sciences (MP), Medical University of South Carolina, Charles- ton, South Carolina; Behavioral Sciences and Health Education Depart- ment (DL), Rollins School of Public Health of Emory University, Atlanta, Georgia; and Howard Hughes Medical Institute (KJR), Chevy Chase, Maryland.

Address correspondence to Barbara O. Rothbaum, Ph.D., Emory University School of Medicine, Trauma and Anxiety Recovery Program, 1256 Briar- cliff Road, Atlanta, GA 30306; E-mail: [email protected].

tReceived Mar 15, 2012; revised Jun 1, 2012; accepted Jun 5, 2012.

0006-3223/$36.00 http://dx.doi.org/10.1016/j.biopsych.2012.06.002

Pharmacologic prevention studies have tested early administra- ion of propranolol, a �–adrenergic blocker, with contradictory results 5– 8). A well-controlled study by Hoge et al. (8) found no benefit of ropranolol over placebo. Early administration of hydrocortisone has hown promise in reducing chronic stress and PTSD symptoms in ardiac surgery patients (9) and emergency room patients (10) but ore research is needed. Nonrandomized studies of morphine and

etamine administration show some association with reduced PTSD ates, but controlled studies are needed (11–13).

Pilot studies of brief psychosocial interventions have been con- ucted as well. A memory-restructuring intervention developed by idron et al. (14) demonstrated some preliminary support in a pilot

tudy, but follow-up research found no intervention effect (15). sychoeducation delivered via self-help booklets has not proven seful as a prevention strategy (16,17). A video-based intervention roviding psychoeducation to rape victims immediately before a

orensic rape exam has shown preliminary support (18,19) but ould not apply to other trauma types. The most successful psy-

hosocial interventions thus far have been brief cognitive-behav- oral therapies (CBT) implemented with individuals who meet crite- ia for acute stress disorder (ASD) and typically include four to six essions of techniques such as psychoeducation, exposure therapy, ognitive therapy, and stress management (20). Cognitive-behav-

oral therapy approaches are typically initiated within 2 to 4 weeks f the initial trauma and have been shown to be superior to sup- ortive counseling (21,22). However, a study with female assault urvivors (23) found that although early CBT accelerated recovery ates compared with supportive counseling, rates of PTSD severity ere equivalent at a 9-month follow-up. A recent randomized trial

ested cognitive therapy, prolonged exposure, and a wait-list con- rol group versus a selective serotonin reuptake inhibitor and pill lacebo condition approximately 1 month posttrauma and found

hat only the two psychological interventions were effective at

BIOL PSYCHIATRY 2012;72:957–963 © 2012 Society of Biological Psychiatry

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reducing PTSD rates compared with placebo or wait-list (24). While CBT seems promising, it has only been tested with individuals al- ready diagnosed with ASD 2 to 4 weeks posttrauma. Therefore, there are currently no good candidates for immediate intervention following trauma exposure.

In basic and experimental research, exposure to the conditioned stimulus in the absence of the unconditioned stimulus is referred to as extinction training. As a therapeutic technique in humans, we refer to it as exposure therapy. Research has established that expo- sure therapy, which relies on fear extinction through engagement with traumatic memories and cues, is an efficacious treatment for PTSD (25). Posttraumatic stress disorder may be viewed as a failure of recovery caused, in part, by a failure of fear extinction following trauma (26). This is supported by animal research demonstrating early extinction training has the potential to modify consolidation of the original fear memory (27). In this study, rats were fear condi- tioned and then given extinction training either 10 minutes, 1 hour, 24 hours, or 72 hours after acquisition, and their fear was evaluated. Animals extinguished at 72 hours exhibited robust indices of fear, whereas animals extinguished at 10 minutes exhibited none of the indices of fear. The lack of fear indices in the short-interval group would seem to be explained most parsimoniously in terms of pre- vention of consolidation of the fear memory. Perhaps, consistent with this, evidence is emerging for a neurobiological difference between short- and long-interval extinction. Cain et al. (28) re- ported that immediate extinction is not affected by the L-type voltage-gated calcium channel inhibitor nifedipine, and another study (29) found that fear extinction initiated 1 hour after fear acquisition reversed a fear conditioning-induced change in a par- ticular glutamate receptor (the glutamate receptor 1 subunit of the �-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor) within the amygdala. This reversal did not occur when extinction was initiated 24 hours after acquisition.

A translational study with humans indicated that participants who received extinction training 10 minutes after fear conditioning had significantly lower fear-potentiated startle than participants receiving extinction training after 72 hours (30). Despite these promising findings, no studies to date have examined the potential of early extinction training in preventing the development of PTSD in recent trauma survivors.

For chronic PTSD, practice guidelines point to CBT as efficacious, with prolonged exposure (PE) having particularly strong evidence as a first-line treatment for PTSD (31,32). Prolonged exposure, which requires repeatedly confronting memories and reminders of the traumatic event, shares similarities with extinction training but is quite distinct from PD. Rose et al. (4) speculate that adverse effects found in PD may be due to intense imaginal exposure in single debriefing sessions, without opportunity for habituation and emo- tional processing, which are emphasized as important mechanisms underlying the effectiveness of exposure therapy. Preliminary evi- dence supports the use of exposure for individuals with ASD (21– 23,33). An initial pilot feasibility study of an exposure-based treat- ment for patients presenting to an emergency department (ED) within hours of a traumatic event indicated that those who received the intervention had lower levels of depression and clinician-rated distress 1 week later (34). However, no randomized controlled stud- ies of exposure therapy in the immediate aftermath of trauma have been conducted to date.

This translational randomized controlled study examined whether the use of modified prolonged exposure therapy in an ED setting in patients experiencing a DSM-IV criterion A trauma would significantly reduce the severity of posttraumatic stress reactions at

4 and 12 weeks posttrauma. Due to estimated depression comor- f

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idity rates of 44.5% in PTSD patients 1 month posttrauma (35), epression rates were also assessed. We predicted that patients

eceiving the intervention would have reduced severity of post- raumatic stress at 4 and 12 weeks posttrauma and reduced severity f depression at 4 weeks posttrauma compared with patients who ere repeatedly assessed without intervention.

ethods and Materials

tudy Design Participants aged 18 to 65 who presented to the ED within 72

ours of experiencing a trauma and met criterion A of the DSM-IV 36) were screened for eligibility (see Figure S1 in Supplement 1). atients who spoke English, had a memory of the event, and were lert and oriented were included in the study. Information on exclu- ion criteria was obtained via patient self-report or documentation n medical charts. The most common reasons for exclusion were not

eeting criterion A for PTSD (n � 1737), loss of consciousness onger than 5 minutes (n � 1076), current intoxication (n � 655), nd failure to meet age criteria (n � 978). Among patients who eclined (n � 1221), the most common reasons cited included lack f interest in receiving intervention (n � 425), being in too much ain (n � 205), and wanting to leave the hospital as soon as possible

n � 224). More information on screening and enrollment is re- orted in Malcoun et al. (37). Acutely injured criterion A trauma atients receiving care in the ED were randomized to receive mod-

fied PE or assessment only.

etting This study was conducted at a public hospital ED with the

argest Level I Trauma Center in Georgia. The hospital research versight committee and university Institutional Review Board ap- roved this investigation. The study was registered at clinicaltrials. ov, NCT00895518.

rocedure Screening and Enrollment. Patients were screened for eligi-

ility by one of three assessors with a minimum of a master’s degree n psychology or social work. Staff were positioned in the trauma rea of the ED from 7:00 AM to 7:00 PM daily. Assessors identified otential patients via the tracking board and interviewed inter- sted patients for eligibility. Participants provided written informed onsent, completed the initial assessment, and were compensated 20 for their time.

Initial Assessment. Assessors collected demographic infor- ation, baseline depression and peritraumatic distress symptoms,

nd trauma history at the initial assessment. Envelopes containing omputer-generated patient random assignments (either to imme- iate intervention or assessment only) were given to the patient nd their nurse after the initial evaluation to ensure that assessors emained blind. The on-call therapist immediately provided the ntervention to those assigned to this condition.

Intervention. Therapists were trained in PE (38,39) and this odified protocol and had a master’s or doctoral degree in psychol-

gy or social work. Patients received three, hour-long sessions of a odified PE intervention, distributed 1 week apart. See Table 1 for a

etailed description of the intervention. Approximately 85% of par- icipants were compliant with all homework assignments, or were

issing only one component, at both follow-up sessions. Follow-up Assessments. Blinded assessors administered the

pdate Trauma Interview (40), the PTSD Symptom Scale-Interview ersion (PSS-I) (41), the Posttraumatic Stress Diagnostic Scale (PDS)

42), and the Additional Treatment Inventory (40) 4 and 12 weeks

ollowing enrollment in the ED. Patients were given the Beck De-

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pression Inventory-II (BDI-II) (43) at the 4-week follow-up to assess epressive symptoms. Approximately 88% of 4-week follow-ups nd 84% of 12-week follow-ups were conducted in person. In cases here a participant was unable to return for follow-up in person,

he option to conduct the interview by phone (n � 7 at 4 weeks, n � 0 at 12 weeks) or by mail (n � 5 at 4 weeks, n � 5 at 12 weeks) was

offered to minimize missing data. Patients meeting DSM-IV criteria for PTSD at the 3-month follow-up were offered the full nine-ses- sion PE treatment (38,39) at no charge.

Measures Outcome measures were gathered via clinical interview and

self-report. Information entered into the database was cross- checked by a second rater to ensure consistency of coding and accuracy. All assessments were audio recorded for reliability.

Trauma Interviews. The Standardized Trauma Interview (40) is 41-item clinician-administered interview gathering information

n relevant aspects of the trauma and demographic information at aseline. For the current study, interrater agreement across three

ndependent raters was .99. The Update Trauma Interview (40) is a 0-item version of the Standardized Trauma Interview used to ather posttrauma information. Interrater agreement across three

ndependent raters was .99. The Additional Treatment Inventory 40) consists of three questions assessing additional treatment ought after the completion of study treatment.

Posttraumatic Stress Diagnostic Scale. This 49-item self-re- ort yields a DSM-IV PTSD diagnosis and PTSD severity and screens

or prior traumatic events. The PDS has high internal consistency. est-retest reliability was good, from .74 to .85. High diagnostic greement (82%) with the Structured Clinical Interview for DSM

Table 1. Modified Prolonged Exposure Session Outline

Session Task

1–1 hour Introduce the intervention (2 min) Imaginal exposure (30–45 min) Process the imaginal exposure (10–15 min) Identify behavioral exposure(s) for the coming week (5

min) Explain normal reactions to trauma and identify self-care

tasks for the coming week (3 min) Breathing retraining (5 min) Schedule next session and remind patient to maintain

the blind (1 min) –1 hour Review homework (5 min)

Imaginal exposure (30–45 min) Process the imaginal exposure (10–15 min) Identify behavioral exposure(s) for the coming week (3

min) Identify self-care tasks for the coming week (3 min) Schedule next session and remind patient to maintain

the blind (1 min) –1 hour Review homework (5 min)

Imaginal exposure (30–45 min) Process the imaginal exposure (10–15 min) Identify behavioral exposure(s) to continue working on

after treatment ends (3 min) Identify self-care tasks to continue prioritizing in the

coming weeks/months (3 min) Remind the patient to attend 4- and 12-week

assessments and to maintain the blind (1 min)

Component lengths varied based on the individual needs of each pa- ient. Total session length is recommended to not exceed 1 hour.

isorders was noted (42). e

Childhood Trauma Questionnaire. The Childhood Trauma uestionnaire (44), a 28-item retrospective self-report, assesses five

ategories of negative childhood experiences: emotional neglect, motional abuse, physical neglect, physical abuse, and sexual buse and has excellent psychometric properties (45– 47).

Immediate Stress Reaction Checklist. The Immediate Stress eaction Checklist (ISRC), a 26-item self-report, examines acute tress responses regarding the current presenting trauma (dissoci- tion, re-experiencing, avoidance, and hyperarousal). Items are ated from 0 (not true) to 2 (very or often true). The ISRC demon- trates strong internal consistency (.86) (48).

Beck Depression Inventory, Second Edition. This 21-item elf-report assesses depression symptoms in the past 2 weeks with xcellent psychometric properties (43,49).

PTSD Symptom Scale-Interview Version. The PSS-I is a clini- ian-administered inventory corresponding to the 17 DSM-IV PTSD ymptoms, each rated on a 0 to 3 scale, with excellent psychometric roperties (50). Interrater agreement across three independent rat- rs was .99 in the current study. The PSS-I has been utilized as both continuous measure of symptom severity, as well as to assess for iagnostic status, and shows moderate to high agreement with the tructured Clinical Interview for DSM Disorders and Clinician-Ad- inistered PTSD Scale interview (50).

ata Analytic Plan The data were initially screened for differences across the con-

itions (intervention/assessment) in baseline measures of child- ood trauma, initial stress reaction, depression, and PTSD from past

raumas. Variables found to significantly differ among the groups at � .15 were included as covariates in all subsequent analyses.

Baseline symptom levels for PTSD could not be validly obtained ue to assessment within hours of trauma exposure. Baseline PTSD ymptoms from past trauma exposure (assessed on the PDS) were ncluded as covariates. Missing values for week 4 and week 12 data

ere handled with multiple imputation. The NORM (51) software ackage was used to generate 100 complete datasets in which emographic variables, pretreatment self-report measures, treat- ent condition, and trauma type were used as auxiliary variables.

stimates were pooled using the guidelines of Rubin (52). Linear ixed-effect models were used to obtain predicted mean values for

utcomes at each assessment point (weeks 4 and 12). Within each odel, time and treatment condition were included as fixed effects

s well as a time � treatment interaction. Covariates in the model ncluded trauma type and variables that were found to differ mong the intervention and assessment groups at baseline. In all odels, a random effect was included for intercept and time. All

omparisons were planned and a Benjamini and Hochberg (53) pproach was used to address issues of multiple comparisons. This pproach provides better control of type I error rates when con- ucting multiple hypothesis tests as compared with more conser- ative approaches (54).

esults

ubjects Average time since trauma (in hours) was mean (M) � 11.79

median � 6.92; SD � 12.90) for the entire sample, with no signifi- ant differences between assessment and intervention groups, (128) � .66, p � .51. The majority of the sample (88%) was enrolled ithin 24 hours posttrauma. Of the 137 participants who were

nrolled in the study, 102 (74%) completed 4-week follow-up and 1 (66%) completed 12-week follow-up. No significant group differ-

nces in dropout rates were detected, �2 � 1.92, p � .17. No pa-

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tients reported a desire to withdraw from the study as a result of their participation, and no study-related adverse effects were re- ported. Demographic information is presented in Table 2.

Table 2. Sample Demographic Information

Intervention (n � 69)

Assessment (n � 68)

Male, n (%) 25 (36.20%) 23 (33.80%) Female, n (%) 44 (63.80%) 45 (66.20%) Age, Mean (SD) 30.17 (12.08) 32.78 (11.12) Ethnicity

White, n (%) 5 (7.20%) 13 (19.10%) Black, n (%) 56 (81.2%) 52 (76.50%) Native American, n (%) 2 (2.90%) 0 (0%) Other, n (%) 6 (8.70%) 3 (4.40%)

Marital Status Single, n (%) 48 (69.56%) 38 (55.88%) Married or cohabitating,

n (%) 13 (18.84%) 24 (35.30%)

Divorced or separated, n (%) 4 (5.80%) 2 (2.94%) Other, n (%) 4 (5.80%) 4 (5.88%)

Minutes Since Presenting Trauma

751.95 (803.04) 663.55 (747.73)

Trauma Type Rape, n (%) 28 (40.58%) 19 (27.90%) Nonsexual assault, n (%) 19 (27.54%) 18 (26.50%) Motor vehicle accident, n (%) 20 (28.98%) 26 (38.20%) Other, n (%) 2 (2.90%) 5 (7.4%)

Prior Trauma Exposure Rape, n (%) 10 (14.5%) 7 (10.3%) Nonsexual assault, n (%) 9 (13.0%) 9 (13.2%) Motor vehicle accident, n (%) 7 (10.1%) 15 (22.1%) Other, n (%) 4 (5.8%) 2 (2.9%) No prior trauma, n (%) 39 (56.5%) 35 (51.5%)

Table 3. Comparison of PTSD for Current Trauma, Depression, and PTSD fo

Intervention (n � 69)

Primary Outcomes PSS-I

Week 4 19.09 � 1.83a,c (15.51–22.68) Week 12 15.47 � 1.98a,d (11.60–19.34)

BDI-II Baseline 18.60 � 1.51a,c (15.64–21.55) Week 4 15.04 � 1.70b,d (11.72–18.37)

PDS Baseline 18.90 � 1.80a,c (15.35–22.39) Week 4 18.90 � 2.34a,c (14.30–23.50)

Baseline Covariates ISRC-Numbing 3.10 (.23) ISRC-

Depersonalization 1.97 (.21)

IRSC-Dissociation 2.33 (.22) ISRC-Re-experiencing 4.84 (.17) CTQ 48.52 (2.91)

�Values are standard errors. Values in parenthesis are 95% confidence datasets generated from multiple imputation. N � 137 participants. Estima

BDI-II, Beck Depression Inventory-II; CTQ, Childhood Trauma Questio Diagnostic Scale; PSS-I, PTSD Symptom Scale-Interview Version.

aSignificant main effect for group at p � .05 based on findings from mix bSignificant main effect for group at p � .05 based on findings from mix c

Significant main effect for time at p � .05 based on findings from mixed-effe dSignificant main effect for time at p � .05 based on findings from mixed-effe

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emographic and Clinical Characteristics A logistic regression demonstrated no significant differences in

aseline demographics between conditions. Univariate analyses of ariance suggested that assessment and intervention conditions iffered on ISRC numbing [F (1,135) � 4.39, p � .05] and ISRC re- xperiencing [F (1,135) � 6.70, p � .01]. Immediate Stress Reaction hecklist peritraumatic depersonalization [F (1,135) � 3.09, p � .08] nd the ISRC postevent dissociation approached significance

F (1,135) � 3.33, p � .07]. Notably, the ISRC responses were higher n the intervention condition compared with the assessment con- ition, suggesting that the intervention group may have had more evere trauma reactions during the peritrauma period. These vari- bles were included as covariates in all subsequent models. To nsure treatment adherence and competence, 20% of therapy ses- ions were rated for treatment integrity. Using a scale from 1 (very oor) to 7 (excellent), mean therapist skill and adherence was rated s 6.19 (SD � .83) or very good.

fficacy Analysis A mixed-effect model was used to assess differences in PSS-I

cores at the 4- and 12-week follow-up assessments controlling for ovariates (Table 3). A significant main effect was found for time p � .04) and for treatment condition (p � .02). Intervention group articipants reported significantly lower PSS-I scores at the 4-week

ollow-up (M � 19.09, 95% confidence interval [CI], 15.51 to 22.68) han the assessment group (M � 24.54, 95% CI, 21.22 to 27.87). imilar results were obtained for the 12-week follow-up, with the

ntervention group (M � 15.47, 95% CI, 11.60 to 19.34) having ignificantly lower scores than the assessment group (M � 20.33, 5% CI, 16.79 to 23.87). The time � treatment condition was not ignificant (p � .29). Effect size estimates for differences at week 4 nd week 12 for the PSS-I suggested treatment had a medium effect 4-week d � .38, 12-week d � .34). A similar approach was used to valuate differences in BDI-II and PDS scores from baseline to week . For the BDI-II, a significant main effect was found for time (p � .02)

r Trauma Across Intervention and Assessment Conditions

Assessment (n � 68) Effect Size

24.54 � 1.70b,c (21.22–27.87) .38 20.33 � 1.80b,d (16.79–23.87) .34

21.26 � 1.47a,c (18.38–24.14) 21.37 � 1.63a,c (18.38–24.14) .35

19.46 � 1.78a,c (15.97–22.95) 23.76 � 2.29a,c (19.27–28.24) .11

p Value 2.50 (.22) .06 1.55 (.16) .1

1.89 (.20) .11 4.20 (.21) .02

48.87 (2.60) .91

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and for treatment condition (p � .01). The intervention group (M � 5.64, 95% CI, 11.71 to 18.37) reported significantly lower BDI-II cores than the assessment group at week 4 (M � 21.37, 95% CI, 8.38 to 24.14). Effect size estimates for week 4 differences on the DI-II indicated a medium effect for treatment (d � .35). For the DS, assessing PTSD symptoms from a prior trauma, there was not a ignificant main effect for treatment (p � .11), or time (p � .98), or a ime � treatment interaction (p � .16). Effect size estimates sug- ested that treatment had a small effect on PDS scores at week 4 (d �

11). Taken together, the findings of the current study support the ypothesis that the intervention reduced posttraumatic stress and epression symptoms.

TSD Diagnosis A PTSD diagnosis was indicated by a response of 2 or greater on

he PSS-I on at least one of the four re-experiencing items, three of he six avoidance items, and two of the five hyperarousal items. sing these criteria, 54% of the intervention condition and 49% of

he assessment condition did not meet criteria for PTSD at week 4. his difference was not significant, �2 � .28, p � .60. At week 12, 4% of the intervention condition and 53% of the assessment con- ition did not meet criteria for PTSD. This difference was statistically ignificant, �2 � 4.16, p � .04. Using these values, the number eeded to treat with this approach at weeks 4 and 12 were 20 and 5,

espectively. Clinically significant depression was defined as a score f 13 or greater on the BDI-II (55). Using these criteria, 51% of the

ntervention condition and 32% of the assessment condition did ot meet criteria for depression. This difference approached signif-

cance, �2 � 3.04, p � .08. The number needed to treat for depres- sion at week 4 was six. Comorbid depression and PTSD diagnoses were identified for 41.76% of the sample.

Follow-up analyses were conducted to determine the impact of treatment across different types of trauma (Figure 1). To accommo- date the reduced power for these analyses, independent compari- sons were made for the 4-week and 12-week trauma symptoms, using the previously described alpha correction. For rape victims (n � 47), those in the intervention condition (M � 20.10, SE � 2.38) eported significantly lower (p � .01, Cohen’s d � .70) PSS-I scores han those in the assessment condition (M � 30.45, SE � 2.73) at eek 4. Similar findings were obtained at week 12, with interven-

ion participants (M � 16.63, SE � 3.05) reporting significantly

0

5

10

15

20

25

30

35

Week 4 Week 12 Week 4 Week 12 Week 4 Week 12

Sexual Assault Transportation Physical Assault

Assessment Interventionp = 0.004

p = 0.05 p = 0.06

p = 0.52

p = 0.43 p = 0.44

Figure 1. Group differences in posttraumatic stress disorder severity at week 4 and week 12 as a function of trauma type. Error bars correspond to � 1 SE.

ower (p � .05, Cohen’s d � .52) scores than the assessment condi- a

ion (M � 25.04, SE � 3.37). For victims of transportation accidents n � 46), the difference between the intervention condition (M � 7.95, SE � 2.66) and assessment condition (M � 24.14, SE � 1.95) pproached significance (p � .06, Cohen’s d � .49) at week 4. owever, there were no significant differences among the groups t week 12 (p � .43, Cohen’s d � .33). For physical assault victims

n � 37), there were no significant differences at week 4 (p � .52, ohen’s d � .14) or at week 12 (p � .44, Cohen’s d � .10). The sample ize for the other trauma group (n � 7) was not sufficient to allow for omparisons.

iscussion

Trauma survivors at an ED in a Level I Trauma Center were andomly assigned to a modified prolonged exposure intervention r assessment only within 11 to 12 hours, on average, of experienc-

ng a severe traumatic event. Those receiving the modified PE inter- ention reported significantly less PTSD and depression severity in he months following the trauma than those assigned to assess-

ent only. These findings suggest that this early intervention is ffective at reducing symptoms of posttraumatic stress at 1 and 3 onths posttrauma and depression at 1 month posttrauma, is safe,

nd is feasible. Higher effect sizes for the intervention were found mong rape victims, which is noteworthy given that rape has been

dentified as the trauma most likely to lead to the development of TSD (1). The intervention targeted the trauma that brought pa- ients into the ED and did not appear to affect PTSD symptoms ssociated with prior traumatic events.

These results have important implications for research on the mmediate response to trauma. First, this is the first behavioral ntervention delivered in the hours following trauma exposure that as been shown to be effective at reducing posttraumatic stress

eactions. Because some studies indicated the possibility that early nterventions such as debriefing could interfere with natural recov- ry following trauma exposure (56,57), the field has shied away rom early intervention studies. However, debriefing is very differ- nt from the therapeutic exposure used herein, and it is our hope hat these promising results will now reopen this important thera- eutic question. Our modified PE is quite distinct from debriefing in

hat it is based on individual versus group delivery, includes other omponents (breathing relaxation, in vivo exposure, attention to ognitions, self-care), and importantly, involves multiple repetition f the trauma narrative to allow for fear extinction within and be-

ween sessions for homework. Second, the intervention and the timing of the intervention are

ased both on translational and clinical research. Exposure therapy as received more empirical support than any other intervention

or ASD and PTSD but has never been attempted within hours of the raumatic event. Basic and preclinical research have indicated that he timing of extinction training following fear conditioning is crit- cal. Myers et al. (27) identified signs of fear in animals given extinc- ion training after 72 hours but not in those given extinction train- ng after 10 minutes. This very early extinction training may be rotective against the physiological and psychological effects of

raumatic fear memories (27). Similar to extinction training, expo- ure therapy is theorized to reduce PTSD symptoms by promoting ear activation and habituation of conditioned fear reactions hrough engagement with traumatic memories, while allowing in- egration of corrective information regarding the trauma (58). Al- hough several mechanisms may be involved, we suggest that the

odified PE intervention presented here may be able to prevent he development of PTSD through similar mechanisms by encour-

ging engagement with the trauma memory and providing an

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opportunity for fear habituation and processing of unhelpful cog- nitions, thus modifying the memory before it is consolidated.

Some limitations should be noted. Since we felt that it would not be valid to measure PTSD symptoms within hours of trauma expo- sure, no baseline measure of PTSD was collected. Thus, we are unable to calculate symptom improvement from baseline to fol- low-up and must depend on between-group comparisons at fol- low-up assessments. The current findings also identified higher immediate stress reactions among intervention participants, which may have allowed more room for improvement, although these initial differences were controlled for statistically.

Because of the pilot nature of this study and the desire to mini- mize participant burden, this study was not able to assess the im- pact of the intervention on other outcome measures, such as func- tioning. In addition, dropout rates were substantial, although complete data were obtained at the 4-week follow-up for the ma- jority of our sample (74%). Such rates are similar to those of other recent large-scale trials that recruited patients shortly after trauma exposure (24,59).

Similarly, the current study’s sample size was not sufficiently powered to detect the smaller effects that were observed on some of the outcome measures such as the PDS. It is unclear if a type II error was committed in retaining the null hypothesis for these analyses. Replication of these findings in larger samples is needed to confirm their reliability. Additionally, future studies examining reduction of posttraumatic stress reactions in the acute aftermath of trauma exposure should be powered for small effects.

This study may have benefited from a longer follow-up period. However, the decision to conduct a 12-week follow-up was made based on research suggesting that by 3 to 4 months posttrauma, PTSD symptoms have typically become chronic and are unlikely to recover spontaneously (2,56,60). The lack of 24-hour ED coverage is another limitation, although most patients arriving overnight could be screened in the morning before discharge.

In addition, because the current study was aiming to answer the question of whether PTSD can be prevented by intervening before memory consolidation, our intervention was specific to the pre- senting trauma only and limited by three brief sessions. Memories from past traumatic events were not addressed, and thus, not sur- prisingly, the intervention effects did not generalize to PTSD symp- toms associated with prior traumas.

Lastly, the public health reach of this intervention may be lim- ited, providing the most benefit to patients most at risk (61). Ex- panding the reach of early intervention should be a focus of further research.

Clearly, more research is needed, particularly to determine who requires early intervention and who will recover naturally without using valuable resources unnecessarily, what is the optimal window for intervention, how many sessions are needed, and what types of treatment are needed for which patients. It will be important to test this early intervention in the field, with both civilians and military personnel, and with delivery by nonprofessionals or paraprofes- sionals to increase dissemination. Larger studies that can examine and confirm specific mechanisms of change are also greatly needed. A long-standing hope of mental health research is to pre- vent the development of psychopathology in those at risk (second- ary prevention) instead of being limited to symptom treatment after disease onset (tertiary prevention). Although further research is needed, this prevention model could have significant public health implications. Work is needed to determine the best policy and practice guidelines for implementation of this type of early

intervention. Translational research providing new approaches to

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ntervention before memory consolidation may provide such an pproach with PTSD.

This study was supported by National Institute of Mental Health rant Number R34 MH083078, “Effects of Early Psychological Interven-

ion to Prevent PTSD,” and the Emory Center for Injury Control, Center or Disease Control Grant Number 5R49CE001494. Dr. Rothbaum had ull access to all of the data in the study. Dr. Price is supported by 32MH018869.

The authors report no biomedical financial interests or potential onflicts of interest.

Clinicaltrials.gov: Examining the Effectiveness of an Early Psycho- ogical Intervention to Prevent Post-Traumatic Stress Disorder; http:// linicaltrials.gov/ct2/show/NCT00895518?term�rothbaum&rank�1; CT00895518.

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