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Carlson K, Kehle S, Meis L, et al. The Assessment and Treatment of Individuals with History of Traumatic Brain Injury and Post-Traumatic Stress Disorder: A Systematic Review of the Evidence [Internet]. Washington (DC): Department of Veterans Affairs (US); 2009 Aug.

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The Assessment and Treatment of Individuals with History of Traumatic Brain Injury and Post-Traumatic Stress Disorder: A Systematic Review of the Evidence [Internet].

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This topic was nominated by the Center for Chronic Disease Outcomes Research, Minneapolis VA Medical Center, in consultation with the Polytrauma/Blast-related Injuries QUERI and the VA Evidence Synthesis Program. The key questions and scope of this review were refined based on input from Technical Advisory Panel members Matthew Friedman, MD, Robin Hurley, MD, Nancy Bernardy, PhD, and Katherine Helmick, MS, CNRN, CRNP.

The final key questions were:

  • 1) What is the observed prevalence of comorbid TBI and PTSD? Does the reported prevalence vary by study population, trauma etiology, TBI severity, or methods of case ascertainment?
  • 2a) What is known about the relative accuracy of diagnostic tests used for assessing mTBI when comorbid with PTSD?
  • 2b) What is known about the relative accuracy of diagnostic tests used for assessing PTSD when comorbid with mTBI?
  • 3a) Are there psychosocial or pharmacological therapies used for treatment of mTBI and PTSD simultaneously?
  • 3b) Are therapies for treatment of mTBI effective when mTBI is comorbid with PTSD? Is there evidence of harms?
  • 3c) Are therapies for treatment of PTSD effective when PTSD is comorbid with mTBI? Is there evidence of harms?


A study search coordinator developed the search strategy with input from the principal investigators (Appendix A). We searched PubMed, PsycINFO, and REHABDATA databases for articles published from 1980 to June, 2009. The search was limited to studies involving human subjects and published in English. Reference lists from studies related to the key questions were searched for additional research studies. TBI was operationalized as a history of confusion, disorientation, or loss of consciousness resulting from a force to the head.43 Included studies must have enrolled participants with a self-reported history of probable TBI, or diagnosed TBI history, regardless of the presence of current TBI-related symptoms. PTSD was operationalized as the development of symptoms characterized as Post-traumatic Stress Disorder by the Diagnostic and Statistical Manual (DSM-III, DSM-III-R, DSM-IV, or DSM-IV-TR).44–47 Included studies must have had participants with DSM-III or DSM-IV diagnoses of or positive screens for PTSD as determined through semi-structured interview, clinical diagnosis of PTSD, or scores exceeding cutoffs indicating probable diagnosis of PTSD on self-report inventories.

A description of the search strategy used to identify ongoing and unpublished research studies is presented in the Active Research section below.


Titles and abstracts (when available) from all references identified in the literature search process were reviewed by a study investigator (KC, SK, LM). The initial screening was designed to identify peer-reviewed, English language articles published after 1980 that included an adult population with probable or diagnosed history of TBI and probable or diagnosed PSTD and were related to one or more of the key questions or that might provide background information. Studies of all design types were considered. Full-text versions of articles that potentially met these criteria were then obtained for further review. We excluded studies if they included more than 10% of subjects less than age 18 years, did not enroll individuals with a history of probable TBI or probable or diagnosed PTSD, or did not present results in a manner that addressed the key questions. Studies that did not meet inclusion criteria for key questions but were considered of special relevance because they were of high methodologic quality or provided evidence potentially, but not directly, relevant to the key questions were included as secondary results.


A content expert abstracted data onto standardized forms (Appendix B) from each article that met the study selection criteria. Results were reviewed with another member of the research team. For Key Question #1, we abstracted the study setting and overall population (e.g., military, veteran, civilian), as well as population demographics (gender, age, race/ethnicity, education level, disability seeking status, presence of pain or mental health disorders other than PTSD), trauma etiology (e.g., combat, terror, motor vehicle, assault), severity of TBI (mild, moderate, severe, and how defined), number of and time since trauma(s), and method(s) used to ascertain, define, and enumerate TBI and PTSD cases (administrative data, self-report, clinical screening, structured interview, neuropsychiatric evaluation). Numerator (TBI/PTSD) and denominator (total study population) data were collected to allow reporting of prevalence by study population. We included studies that assessed for PTSD in patients with a reported history of TBI as well as studies that assessed for both TBI and PTSD across more heterogeneous patient populations.

We attempted to address Key Question #2 using established methods as outlined by Bossuyt et al.47 and Leeflang et al.48 Population, trauma, and case assessment data were abstracted as defined for Key Question #1. In addition, if reported, we noted the operationalized cut-off scores for tests used to diagnose mTBI and/or PTSD (including screening instruments, clinical interviews, neuropsychological batteries), the names of diagnostic reference tests used for comparison, and the operationalized cut-off scores for these reference tests. Other data we sought to abstract included whether those administering tests for mTBI or PTSD were blinded to results of the other assessment methods, the time interval between administration of the tests, whether treatments were received between tests, and the methods used to calculate or compare the diagnostic accuracy and statistical uncertainty. We attempted to determine if comparator test findings would lead to reclassification of disease/injury presence or treatment versus the control diagnostic test. We sought to examine variability in reports of diagnostic accuracy by population subtype.

For Key Question #3, we included only studies in which at least 80% of the participants were diagnosed with both mTBI and PTSD or the outcomes were stratified for those with both diagnoses. We sought to abstract results from studies of psychological or pharmacological therapies that simultaneously targeted symptoms of mTBI and PTSD or from studies that treated only one of the conditions in individuals with both conditions. Because we expected to identify few studies that would include either a wait-list control or other comparison group, we included studies of treatment outcomes without a comparison group. The outcomes of interest were PTSD symptomology (self-report or clinician-assessed), mTBI symptomology (self-report or objective performance measures), functional status/ability, pain, and quality of life. When data were available, outcomes at baseline, post-treatment, short (one- to six-months), medium (six-months to one year), and long-term (greater than one year) follow-up were recorded. Harms that occurred due to administering a treatment designed for only one of the conditions to a participant with mTBI/PTSD were documented as were the characteristics of the study setting (e.g., veteran or community hospital).


We attempted to rate the quality of randomized controlled trials, cohort studies, and case-control studies as good, fair, or poor based on criteria specific to the study design type.49 Cross-sectional studies, case series, and case reports were considered of low methodologic quality. We assessed studies for applicability to U.S. OEF/OIF veterans. Evidence tables were organized by key questions and conclusions were drawn based on qualitative syntheses of the evidence. We also sought to evaluate the overall quality of the evidence for each main outcome as proposed by the GRADE Working Group.50


We constructed evidence tables showing the study characteristics and results for all included studies, organized by key question, intervention, or clinical condition, as appropriate. We critically analyzed studies to compare their characteristics, methods, and findings. We compiled a summary of findings for each key question or clinical topic, and drew conclusions based on qualitative synthesis of the findings. We did not conduct pooled analyses due to marked heterogeneity in study design, cohort creation, patient demographic characteristics, trauma type, etiology, assessment methodology, and disease/injury definition. We report individual study results and summarize findings across these key variables.


We identified ongoing and/or unpublished funded research related to the key questions by searching the VA HSR&D research database (, the Computer Retrieval of Information on Scientific Projects (CRISP) database (, the Clinical Trials database (, the metaRegister of Controlled Trials (, and the Department of Defense Congressionally Directed Medical Research Program (CDMRP) database. We contacted the HSR&D Program Managers for Long Term Care and Mental Health; individuals associated with the National Center for PTSD; the Physical Medicine and Rehabilitation TBI/Polytrauma Program; the Polytrauma/Blast-Related Injuries QUERI; the War Related Illness and Injury Study Center (WRIISC); and key authors in the field. Members of our Technical Advisory Panel and the Polytrauma/Blast-related Injuries QUERI provided additional contacts. Individuals were contacted once by e-mail and asked to provide a brief protocol or to complete a survey to capture information about related research projects. This survey was adapted from a survey used by the Oregon Evidence-based Practice Center in a systematic review of pain in patients with polytrauma.51 There was no further attempt to contact individuals who did not respond to our initial e-mail request.


A draft version of this report was sent to peer reviewers that included members of our Technical Advisory Panel; participants in the VA consensus conference on practice recommendations for treatment of veterans with mTBI, PTSD, and pain; and Dr. Charles W. Hoge, Director of the Division of Psychiatry and Neuroscience at Walter Reed Army Institute of Research. Peer reviewer comments were compiled, responses were prepared (Appendix C), and resulting edits were incorporated into the final version of this report.

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