The Assessment and Treatment of Individ

History of Traumatic Brain Injury and Post‐t

Stress Disorder

A Systematic Review of the Evidenc

K thl a een F. C l ar son, MS, PhD

Core Investigator

Center for Chronic Disease Outcomes Research

Minneapolis VA Medical Center

May 24, 2010
Acknowledgements

Co-authors/Collaborators• Timothy J. Wilt, MD, MPH• Shannon Kehle PhD

Expert Panel/Revi Matthew Friedman, 

• Shannon Kehle, PhD

 Robin Hurley MD

• Laura Meis, PhD • Nanc

y Greer, PhD 

 Robin Hurley, MD Nancy Bernardy, Ph

y ,

 Katherine Helmick Katherine Helmick, 

• Roderick MacDonald, MS • Indulis Rutks, BA 

,

CRNP

 Nina A. Sayer, PhD

• Joan Barnes, MS S K D b h for the Minneapolis VA Evidence Synthesis



Steven 

K. D

o

bsc

ha

 Charles W. Charles W. Hoge, M

for the Minneapolis VA Evidence Synthesis

Program, Center for Chronic Disease Outcomes Research, Minneapolis VA Medical Center
Funding

• Center for Chronic Disease Outcomes Rese

Minneapolis VAMC 

• VA HSR&D Career Development Program; 

08-025

• VA HSR&D Evidence-based Synthesis Prog
Disclosure
Overview

• VA Evidence‐based Synthesis Program (ESP

• Current Report

– Background– Key questions– Methods– Results– Conclusions– Recommendations for future research

• Q & A
VA Evidence‐based Synthesis Pro

(ESP)

• S d ponsored by VA Office of R&D and HSR&D

• Syntheses of health care topics for VA leaders

• Inform clinical policy, CPGs, future research, perform

measures, and drug formulary decisions

• T i op cs id tifi d identified by HSR&D Fi ld e B d ase S i c ence Ad 

v 

similar advisory groups and by program officials in V

Office

– Topics may also be nominated using form on ESP web site

http://www.hsrd.research.va.gov/publications/esp/TopicNominat

• Conducted by 1 of 4 centers with systematic review 

(Portland, West LA, Durham, Minneapolis)
VA Evidence‐based Synthesis Pro

(ESP)

• Planning and Oversight Committee

– HSR&D, Patient Care Services, OQP, & VISN Clinical & Qu

Management Officers

– Identifies priority issues & ensures quality

• Technical Advisory Panel (TAP)

– Recruited for each topic to provide content expertise– Develop, review, refine, and approve topic and key ques– Review data/draft report

• External Peer Reviewers

– Review and comment on draft report

• Final reports posted on VA HSR&D website:

http://www.hsrd.research.va.gov/publications/esp/
Current Report

The Assessment and Treatment of Individuals with 

Traumatic Brain Injury and Post‐traumatic Stress 

Systematic Review of the Evidence Evidence

(August, 2009)

Full‐length report available on ESP web site

http://www hsrd research va gov/publications/esp/http://www.hsrd.research.va.gov/publications/esp/

2009.pdf
Background

• T ti raumatic B i ra n I j n ury (TBI): Trauma to the h d ea re

alteration or loss of consciousness or post‐traumat

(CDC, 1999)

– F ll a s, motor vehi l c e crashes, blasts

• Blunt force TBI differentiated by level of severity: m

moderate, severe

• Up to 23% of soldiers/veterans reported to have ex

a TBI (mostly mild TBI) (Terrio et al., 2009)

• While most with mild TBI will fully recover, a mino

suffer ongoing post‐concussive somatic, cognitive, 

behavioral symptoms

– Persistent post‐concussive symptoms may be mistaken f

of chronic stress or other mental health disorders
Background

• P t os ‐t ti raumatic Stress Di d sor er (PTSD): A it nx e y di 

so

characterized by re‐experiencing, avoidance, and

hyperarousal symptoms following exposure to a tr

event (APA, 2000)

• Prevalence estimated from 1.4% ‐ 31% of OIF soldi

al., 2009)

• VA treated >100,000 OEF/OIF veterans for PTSD fro

2008 (Kang, 2009)

• There are efficacious treatments for PTSD• Many symptoms of PTSD can also occur among tho

history history of mild TBI (i e. ., anxiety anxiety, insomnia insomnia and fatig

fatig

problems thinking or remembering, irritability, angaggression)
Background

• O l ver ap b t e ween TBI and PTSD has been st di d u e ( 

debated) for many years

– Memory of traumatic event presumed necessary for PTS

absent in more severe cases of TBI

• Continued evidence of comorbid TBI and PTSD acr

populations and TBI severity severity levels

– Same exposures/events– TBI increase suscep y tibility to PTSD?– PTSD increase risk of TBI?

• Clinicians in DoD, VA, and private sector treating p

b h ot condi it ons

– Veterans of OEF/OIF– Mild TBI
Uncertainties

• P l reva ence of comorbid ( ild) m TBI and PTSD unkno

• Unknown whether diagnostic/screening instrumen

assessing assessing history history and symptoms symptoms of mild TBI and PT

accurate if patient has both conditions

– Screening for mild TBI history based on recall of event, w

affected by current current PTSD symptoms symptoms

• Unknown whether evidence‐based treatments for

sy p m tomatic mild TBI and PTSD alone are effective 

conditions co‐occur

– Pharmacologic agents used to treat symptoms of PTSD m

exacerbate exacerbate TBI‐related related cognitive cognitive symptoms symptoms

– Cognitive limitations, problems with emotion regulation 

control, or pain associated with mild TBI may decrease e

PTSD treatments
VA Consensus Conference

• In 2009, expert cli i i n c ans and researchers were con

develop practice recommendations for treatment 

with comorbid mild TBI, PTSD, and pain

• Additionally, a systematic review of evidence was

commissioned through the VA ESP to help provide

background for this conference conference
3 Key Questions

KQ1) What is the prevalence of comorbid TBI and PTS

– Does reported prevalence vary by study population, inj

TBI severity (mild versus moderate/severe), or method

ascertainment?

KQ2) What is the relative accuracy of diagnostic tests 

– Assessing mild TBI when mild TBI is comorbid with PTS– Assessing PTSD when PTSD is comorbid with mild TBI?

KQ3) Are there psychosocial or pharmacological thera

for treatment of mild TBI and PTSD si l 

mu taneo

– Are therapies for treatment of mild TBI effective when 

comorbid with PTSD? Is there evidence of harms?

– Are therapies for treatment of PTSD effective when PTS

with mild TBI? Is there evidence of harms?
Methods

• Key questions, scope, and work plan developed a

with TAP

• Operational definitions:

TBI• confusion, disorientation, or loss of consciousness due to 

h d ea

• studies must have included participants with reported hx 

regardless of current symptoms

PTSD• development of sy p m toms characterized as PTSD by DSM• studies must have included participants with DSM diagno

positive screens for, PTSD as determined through clinical 

structured structured interviews interviews, or scores exceeding exceeding specified specified cut‐o

probable PTSD on self‐report inventories
Methods

• Literature Search

– 2 respective searches of PubMed, PsycInfo, REHABDATA, 

Review databases

• TBI (e g. ., “coma,” “head injuries injuries, closed ) closed”)• PTSD (e.g., “post‐traumatic stress”)

– Results then merged– Limited to English‐language articles presenting primary d

human subjects and published from January, 1980 to Jun

– Reference Reference lists were searched searched for additional additional references references– Expert recommendations were solicited
Methods

• Inclusion/Exclusion Criteria

– All study designs except case report were included

– Studies must have assessed participants for a “probable” 

or diagnosed diagnosed TBI history history, regardless regardless of current current symptoms symptoms

– Studies must have assessed participants for DSM‐III or IV 

PTSD determined through clinical diagnoses or interview

PTSD based on indicated cut‐off scores using self‐report 

screening measures

– Studies were excluded if they did not meet the above cri

did not present data in a manner that addressed key que
Methods

• Data Extraction

– Titles and abstracts reviewed by investigator to select stu

address key questions

– Full text review conducted conducted to determine determine whether whether study m

criteria

– For included studies, data were abstracted onto standard

abstraction forms

Methods

• Outcomes of Interest

– KQ1: Frequency of TBI + PTSD, according to:

• # of injuries/severity (mild vs. moderate/severe)• Etiology (e.g., military vs. civil ) ian• Method and timing of assessment• Patient Patient demographics demographics (e g. ., gender, race, age, educa

educa

– KQ2: Sensitivity, specificity, and disease/Txt rec– KQ3: Improvement Improvement in symptoms symptoms, loss of dx, fun

fun

status, pain, QOL, harms

– Assess study quality and external validity
Methods

• Data Synthesis

– Critically analyzed studies, comparing methods 

and drew conclusions based on qualitative synt

findings

• Heterogeneity across studies precluded pooled analysis or 

ratings

• Emphasis on studies with greatest applicability to mild TBI

OEF/OIF veterans
Results

• Combined reference library contained 1,107 citatio• 32 unique studies, described in 38 references, met 

criteria
Study flow diagram

Excluded (n=749)

Study older than 1980 = 

y g

Search results n=1107

Study older than 1980 

Age < 18 yrs = 61

Probable TBI not included = 

Probable PTSD not included 

Not peer reviewed = 164

Pulled for text review n=358

Not peer reviewed 164

Other = 22

Excluded (n=323)

Pulled for text review n=358 A 18 2ge < 18 yrs = 2

Probable TBI not included = 

Probable PTSD not included 

Not peer reviewed = 5

Oth 150 Other = 150

Included articles found in bibliogrIncluded articles from expert reco

Included references n=38

KQ1: 38 (32 unique studies)

Included articles from expert reco

KQ1: 38 (32 unique studies)KQ2: 0KQ3: 0
Description of Studies

• All 32 studies reported data on frequency of TBI/P

– 24 reported on mild TBI/PTSD

• Involved 10‐2,525 participants (majority <200)• Most were cohort or cross‐sectional studies• Considerable variation in study design

– Participant characteristics

– Trauma etiology

– M th d e o s and ti i m ng of parti i t c pan enroll t men– Methods and timing of TBI and PTSD assessment

• 10 studies studies involved involved US military military personnel personnel and vete

vete

– 3 largest studies involved individuals who served in OEF/

2008; Schneiderman et al., 2008; RAND, 2008)
KQ1: Prevalence

• Frequency of TBI/PTSD ranged from 0% to 70%

– Majority (n=23) reported frequencies <20%– Few reporting reporting frequencies frequencies >50% were small and/or had 

non‐representative study samples

• 3 large studies involving U.S. military/veterans reported 

between 5 and 7%

• 2 largest studies involving non‐military participants rep

f i requencies of 8%
KQ1: Prevalence

• No consistent patterns in frequency of PTSD over t

longitudinal studies of participants with TBI history

• No consit t s en patterns when comparing diff t eren t

etiologies

– 32% to 66% of military military related related TBI also had PTSD– 14% to 56% of non‐military TBI also had PTSD

• No clear patterns in frequency of TBI/PTSD based on method

identification

– 3% to 70% in studies utilizing structured interviews to as

– 5% to 60% in studies studies using self‐report instruments instruments to ass
Frequency of TBI/PTSD Across Studie
KQ1: Prevalence Prevalence (mild TBI/PT

TBI/PT

• Analyses restricted to studies exclusive to individu

history of mild TBI or those that stratified results b

severity

• Frequency of PTSD in individuals with mild TBI hist

from 0 to 89%

– Majority (n=12) reported values between 10% and 40%

• The 3 largest studies involving US OEF/OIF military personne

reported 33% to 39% of individuals with probable mild TBI a

probable PTSD

• The 5 largest largest civilian civilian studies studies reported reported 12% to 27% of individu

individu

TBI also had PTSD
Frequency of PTSD in Subjects with Mild T
KQ2: Diagnostic Accuracy

• No studies examining methods of PTSD assessmen

individuals with mild TBI or methods of mild TBI as

individuals with PTSD
KQ2: Diagnostic Accuracy

Secondary Studies

• Sumpter & M Mill c an (2005) compared rel i at ve acc

PTSD assessment tools in 34 individuals with sever

– Post‐traumatic traumatic Diagnostic Diagnostic Scale (n 20; = 59%)– Impact of Events Scale (n=15; 44%)

– CAPS, criteria B‐F, without clinical judgment (n=6; 18%)

– CAPS, cri i ter a B‐F, wi ht cli i l n ca j du gment ( 1 n= ; 3%)

• Sumpter & McMillan (2006) interviewed participan

identify reasons reasons for false positives positives

– “Curiosity about event” vs. “re‐experiencing”

– Upsetting thoughts re “effects of TBI” vs. “event itself”
KQ3: Treatment

• No studies were identified that examined the effec

therapies for treatment of symptomatic mild TBI o

individuals with both
KQ3: Treatment

Secondary Studies

• Bryant et al. ( ) 2003 conducted a small ( ) n=24 , good

RCT examined effectiveness of 5 weekly CBT sessio

individuals with mild TBI and Acute Stress Disorder 

individuals individuals with ASD have been found to develop develop PTSD)

– Patients receiving CBT developed PTSD at lower rate tha

who received supportive counseling

• Time 1 (immediately (immediately after treatment): treatment): 8% vs. 58%• Time 2 (6 months after treatment): 17% vs. 58%

• Two case reports (1 involving OEF/OIF veteran) tha

use of CBT to treat symptoms of PTSD in indd

ivi ua

TBI (Batten & Pollack, 2008; McGrath, 1997)

– Reported Reported decrease decrease in symptoms symptoms of anxiety anxiety and depressio

depressio

significant residual symptoms remained
Limitations

• Search only through June 2009

• Potential publication bias

• Few population‐based studies

– Poor external validity

• S d tu y popul i at ons, ti i m ng and di i agnostic cri i ter a u

classify TBI and PTSD varied widely

• Key variables variables frequently frequently not reported reported• Study outcomes often not stratified by key variable
Conclusions

• Reported frequencies of TBI/PTSD varied widely

– Observed heterogeneity likely due to variations in study 

– Most studies were not designed to answer question of T

prevalence

• Results of 3 large cross‐sectional studies in OEF/OI

strikingly consistent

– Probable mild TBI/PTSD “population” prevalence of 5‐7%– Probable PTSD in 33‐39% of individuals with probable hi

TBI

• However...

– Cross‐sectional in nature– Case identification based on self‐report screening instru– Response rates ranged from 34% to 59%
Conclusions

• Even without understanding population prevalenc

seem to indicate PTSD is a sub l stantial problem am

with a TBI history

– Most studies studies reported reported probable probable or diagnosed diagnosed PTSD in 10

study participants with probable or diagnosed TBI histor

– 33% ‐ 39% of respondents in 3 large US military/veteran 

• More research needed to help inform provision an

coordination of rehabilitation and mental health se

– Epidemiologic studies to understand population prevalen

– Studies of diagnostic accuracy

– Studies evaluating efficacy and effectiveness vs. harms o
Future Research Needs

• Large, prospective epid i l i idemiologic studies

– Recruit and retain the most representative samples poss– Utilize standard standard definitions definitions and measures measures– Collect and report outcomes by potentially relevant pati

characteristics, etiology and severity of injury, and time s

• Di ti agnostic accuracy st di u es need de th t a utilize est 

gold standard methods

– Efforts will benefit by adhering to Standards for Rep 

ortin 

Accuracy (STARD) statement

• High quality (i.e., randomized and controlled) stud

to evaluate clinical clinical services services

– Start with empirically supported treatments– Also explore facets of clinical effectiveness
THANK YOU!

For more information:

Full Report:

http://www.hsrd.research.va.gov/publications/esp/T

2009 df 2009.pdfTailored Tailored manuscript manuscript presenting presenting results results currently currently in pr

Journal of Head Trauma Rehabilitation

Feel free to contact me: Kathleen.Carlson@VA.GOV