1. Traumatic Brain Injury and Depression
Prepared for:
Agency for Healthcare Research and Quality (AHRQ)
Traumatic Brain Injury and Depression This slide set is based on an evidence report titled Traumatic Brain Injury and Depression that was developed by the Vanderbilt Evidence-based Practice Center for the Agency for Healthcare Research and Quality (AHRQ Contract No I) and is available online at the Effective Health Care Program Web site ( Evidence reports represent comprehensive systematic reviews of the literature and provide comprehensive, science-based information on common, costly medical conditions and new health care technologies. For the evidence report on traumatic brain injury and depression, studies published between January 1, 1966, through May 30, 2010, were identified from searches of PubMed, MEDLINE®, PsycINFO®, EMBASE, CINAHL, and PILOTS for articles published in English. This evidence report included 115 unique publications.
Reference:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:

2. Introduction
There is no clear consensus about the extent to which depression contributes to long-term disability after traumatic brain injury (TBI).
Care providers in a variety of settings need to know:
How often depression develops in patients with a history of TBI.
When and how to best screen for depression among patients with a history of TBI.
The likely outcomes of treatment options for depression among patients with a history of TBI.
Introduction
We do not know the extent to which depression contributes to long-term disability following traumatic brain injury (TBI). Depression is one of several potential psychiatric illnesses that may occur after TBI. Clinicians, caregivers, and patients lack formal evidence to guide the timing of screening, selection of tools for screening and assessment, choice of treatment, and assessment of treatment success.

3. Background: Traumatic Brain Injury
TBI occurs as a result of a blow to the head or other force from an event such as a motor vehicle crash, a sports injury, a fall, an assault, or an explosive blast.
28%
20%
19%
11%
22%
Falls
Motor-vehicle crashes
Being struck by an object
Assault
Other
Background: Traumatic Brain Injury
TBI occurs when an external force—from events such as falls, assaults, motor vehicle accidents, or blasts—injures the brain. It may occur as a result of a direct hit to the head. Rapidly accelerating and decelerating wind, accompanied by pressure changes, may also cause direct injury to the brain or propel other objects into the head (as from a blast). Internal impact of the brain against the skull due to a direct impact to the head or rapid acceleration/deceleration of brain tissue may result in tissue damage, swelling, inflammation, and internal bleeding. Outside of the military theater, TBIs are most commonly associated with falls (28%), motor vehicle-traffic crashes (20%), being struck by objects (19%), and assault (11%).
References:
Langlois JA, Rutland-Brown M, Wald MM. The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil 2006;21:375-8.
Okie S. Traumatic brain injury in the war zone. N Engl J Med 2005;352:
Langlois JA, et al. J Head Trauma Rehabil 2006;21:375-8; Okie S. N Engl J Med 2005;352:

4. Background: Public Health Impact of Traumatic Brain Injury (1 of 2)
TBI is responsible for roughly 1.2 million emergency department visits each year, with one in four patients requiring hospitalization.
Approximately 75% of civilian TBIs are categorized as mild.
Individuals sustaining a mild TBI may not seek clinical care for their injury, leading to an underestimation of the overall impact of TBI.
Background: Public Health Impact of Traumatic Brain Injury (1 of 2)
TBI is responsible for roughly 1.2 million emergency department visits each year, with one in four patients requiring hospitalization. Because most estimates of TBI rates are based on hospital use, some individuals with TBI are not counted because they do not seek care or they seek care in other settings. This may be especially true for patients with mild TBI, particularly in the presence of sports-related injury. The severity of TBIs is most commonly categorized by using the Glasgow Coma Scale (GCS): scores of 13–15 are mild, 9–12 are moderate, and 3–8 are severe. Most TBIs are mild, and the Centers for Disease Control and Prevention (CDC) estimate that 75% of civilian TBIs fall into this category. Much of the research in the nonmilitary population, especially on mild TBI, is derived from the sports injury literature. Because athletes tend to represent a healthier subpopulation, this literature may not be entirely applicable to the general population of individuals who sustain a TBI.
References:
Faul M, Xu L, Wald MM, et al., for the National Center for Injury Prevention and Control. Traumatic brain injury in the United States: emergency department visits, hospitalizations and deaths 2002–2006. Atlanta, GA: Centers for Disease Control and Prevention; March 2010.
National Center for Injury Prevention and Control. Report to Congress on mild traumatic brain injury in the United States: steps to prevent a serious public health problem. Atlanta, GA: Centers for Disease Control and Prevention; September 2003.
Faul M, et al. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths 2002–2006. March 2010; National Center for Injury Prevention and Control. Report to Congress on mild traumatic brain injury in the United States: steps to prevent a serious public health problem. September 2003.

5. Background: Public Health Impact of Traumatic Brain Injury (2 of 2)
Direct and indirect costs associated with TBI are estimated to exceed $56 billion each year.
Among individuals who sustain a TBI, approximately 50,000 die as a result of their injury and 80,000 to 90,000 have a long-term disability.
Currently, more than 5 million survivors of TBI live with chronic disability.
Background: Public Health Impact of Traumatic Brain Injury (2 of 2)
Estimates of direct and indirect costs associated with traumatic brain injury (TBI) exceed $56 billion and may be increasing. Among individuals who sustain a TBI, approximately 50,000 die each year of their injuries and 80,000 to 90,000 have a long-term disability.
References:
Crooks CY, Zumsteg JM, Bell KR. Traumatic brain injury: a review of practice management and recent advances. Phys Med Rehabil Clin N Am 2007;18: , vi.
Faul M, Xu L, Wald MM, et al., for the National Center for Injury Prevention and Control. Traumatic brain injury in the United States: emergency department visits, hospitalizations and deaths 2002–2006. Atlanta, GA: Centers for Disease Control and Prevention; March 2010.
National Center for Injury Prevention and Control. Report to Congress on mild traumatic brain injury in the United States: steps to prevent a serious public health problem. Atlanta, GA: Centers for Disease Control and Prevention; September 2003.
Crooks CY, Zumsteg JM, Bell KR. Traumatic brain injury: a review of practice management and recent advances. Phys Med Rehabil Clin N Am 2007;18: , vi; Faul M, et al. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths 2002–2006. March 2010; National Center for Injury Prevention and Control. Report to Congress on mild traumatic brain injury in the United States: steps to prevent a serious public health problem. September 2003.

6. Background: Traumatic Brain Injury — Sequelae
TBI is often accompanied by symptoms that may be severe or mild.
In cases of mild TBI, the symptoms frequently include nausea, headache, balance problems, blurred vision, memory loss, or difficulty concentrating.
TBIs can exert influence in the short and long term across several domains: physical, cognitive, behavioral, and emotional.
Background: Traumatic Brain Injury: Sequelae
TBI is often accompanied by symptoms that may be severe or mild. In cases of mild TBI, the symptoms frequently include nausea, headache, balance problems, blurred vision, memory loss, or difficulty concentrating. TBIs can exert influence in the short and long term across several domains: physical, cognitive, behavioral, and emotional.
References:
Defense and Veterans Brain Injury Center Working Group on the Acute Management of Mild Traumatic Brain Injury in Military Operational Settings. Clinical practice guideline and recommendations: December 22, 2006 Washington, DC: Defense and Veterans Brain Injury Center; 2006.
Rehabilitation of persons with traumatic brain injury. NIH Consensus Statement Online 1998 Oct 26–28;16:1-41. Available at: Accessed March 10, 2011.
Defense and Veterans Brain Injury Center Working Group on the Acute Management of Mild Traumatic Brain Injury in Military Operational Settings. Clinical practice guideline and recommendations: December 22, 2006; Rehabilitation of persons with traumatic brain injury. NIH Consensus Statement Online 1998 Oct 26–28;16:1-41.

7. Background: Traumatic Brain Injury and Depression
Depression is one possible result of TBI.
Recognition of depression can be confounded by an overlap of the symptoms that result from TBI.
Depression reduces quality of life and impairs ability to function in social and work roles.
In patients requiring physical therapy, depression can undermine rehabilitation planning and treatment adherence.
Background: Traumatic Brain Injury and Depression
Prevalence estimates of post-traumatic brain injury (post-TBI) depression range from 15–77% in the published literature. Depression associated with TBI can manifest soon after injury or well into the future, and reported rates are probably influenced by timing of screening and the tools used. There is evidence to suggest that TBI is associated with high rates of depression and of other axis I and axis II conditions described in the Diagnostic and Statistical Manual for Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR). Furthermore, depression has been noted to be comorbid with other psychiatric conditions, including addiction or anxiety, in a number of studies. Post-TBI depression is thought to be a product of multiple biological factors. Some authors have inquired as to whether post-TBI depression is related to neuroanatomical or pathophysiological changes. Others suggest it is a response to psychosocial factors such as functional loss and inability to progress in rehabilitation.
References:
American Psychiatric Association. Diagnostic and statistical manual for mental disorders. 4th ed. Text revision. Arlington, VA: American Psychiatric Association; 2000.
Busch CR, Alpern HP. Depression after mild traumatic brain injury: a review of current research. Neuropsychol Rev 1998;8:
Gordon WA, Zafonte R, Cicerone K, et al. Traumatic brain injury rehabilitation: state of the science. Am J Phys med Rehabil 2006;85:
Holsinger T, Steffens DC, Phillips C, et al. Head injury in early adulthood and the lifetime risk of depression. Arch Gen Psychiatry 2002;59:
Jorge RE, Robinson RG, Starkstein SE, et al. Depression and anxiety following traumatic brain injury. J Neuropsychiatry Clin Neurosci 1993;5:
Kim E, Lauterbach EC, Reeve A, et al, for the ANPA Committee on Research. Neuropsychiatric complications of traumatic brain injury: a critical review of the literature (a report by the ANPA Committee on Research). J Neuropsychiatry Clin Neurosci 2007;19:
O’Donnell ML, Creamer M, Pattison P, et al. Psychiatric morbidity following injury. Am J Psychiatry 2004;161:
Varney NR, Martzke JS, Roberts RJ. Major depression in patients with closed head injury. Neuropsychology 1987;1:7-9.
American Psychiatric Association. Diagnostic and statistical manual for mental disorders. 4th ed. Text revision. 2000; Busch CR, Alpern HP. Neuropsychol Rev 1998;8:95-108; Gordon WA, et al. Am J Phys med Rehabil 2006;85:343-82; Holsinger T, et al. Arch Gen Psychiatry 2002;59:17-22; Jorge RE, et al. J Neuropsychiatry Clin Neurosci 1993;5:369-74; Kim E, et al. J Neuropsychiatry Clin Neurosci 2007;19:106-27; O’Donnell ML, et al. Am J Psychiatry 2004;161:507-14; Varney NR, et al. Neuropsychology 1987;1:7-9.

8. Background: Recognizing Depression
No single symptom is seen in all depressed patients. Common symptoms include: sadness, persistent negative thoughts, apathy, lack of energy, fuzzy or irrational thinking, and an inability to enjoy normal events in life.
These symptoms may not be recognized as part of depression, which makes identification of the condition challenging.
Depression in patients with a history of TBI may be comorbid with other psychiatric conditions, especially anxiety disorders.
Depressed individuals are at increased risk for suicide.
Following a TBI, active screening is essential for recognition, treatment, and prevention of recurrent depression.
Background: Recognizing Depression
The criteria that define depression likely encompass a heterogeneous set of illnesses. While no single feature is seen in all depressed patients, common features include sadness, persistent negative thoughts, apathy, lack of energy, cognitive distortions, nihilism, and inability to enjoy normal events in life. Especially in a first episode, individuals and families may not recognize the changes as part of an illness, making identification and self-reporting of the condition challenging. Some deficits after head injury can be falsely attributed to neuroanatomical or pathophysiological changes of TBI rather than to depression, leading to misdiagnosis and a missed opportunity for effective treatment. Suicide, the most salient consequence of depression, is usually impulsive and extremely difficult to predict and prevent. In order to recognize and treat post-TBI depression, as well as to prevent its recurrence, active screening is essential.
Reference:
O’Connor EA, Whitlock EP, Gaynes B, Beil TL. Screening for Depression in Adults and Older Adults in Primary Care: An Updated Systematic Review. Evidence Synthesis No. 75. AHRQ Publication No EF-1. Rockville, Maryland: Agency for Healthcare Research and Quality, December 2009.
O’Connor EA. Screening for Depression in Adults and Older Adults in Primary Care: An Updated Systematic Review. Evidence Synthesis No. 75. AHRQ Publication No EF-1. December 2009.

9. Treatment Options for Depression Examined in the Systematic Review
Psychotropic medications
Selective serotonin reuptake inhibitors
Serotonin and norepinephrine reuptake inhibitors
Tricyclic antidepressants
Monoamine oxidase inhibitors
Non–FDA-approved uses of other medications
Psychotherapy
Neuropsychological rehabilitation
Community-based rehabilitation
Complementary and alternative medicine
Neuromodulation therapies
Background: Treatment Options for Depression Examined in the Systematic Review
Potential treatment options for depression examined in this systematic review are drawn from the current armamentarium of treatments for non–TBI-related depression and include: psychotherapy, psychotropic medications, neuropsychological rehabilitation, community-based rehabilitation, complementary and alternative medicine, and neuromodulation therapies. Psychotropic medications may include: selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, monoamine oxidase inhibitors, and other, non–FDA-approved uses of both older and novel medications.
Reference:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness
Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

10. About AHRQ Evidence Report Development and This CME Activity
A systematic review of 115 clinical studies was conducted by independent researchers, funded by the Agency for Healthcare Research and Quality, to synthesize the evidence on what is known and not known on this clinical issue.
This topic was nominated through a public process. The research questions and the results of the report were subject to expert input, peer review, and public comment.
The results of this review are summarized here for use in your decisionmaking and in discussions with patients.
The full report, with references for included and excluded studies, is available at the Effective Health Care Program Web site.
About Agency for Healthcare Research and Quality Evidence Report Development and This CME Activity
Topics are nominated through a public process, which includes submissions from health care professionals, professional organizations, the private sector, policymakers, members of the public, and others. A systematic review of all relevant clinical studies is conducted by independent researchers, funded by AHRQ, to synthesize the evidence in a report summarizing what is known and not known about the select clinical issue. The research questions and the results of the report are subject to expert input, peer review, and public comment. The results of these reviews are summarized in Clinician Guides and Consumer Guides for use in decisionmaking and in discussions with patients, as well as educational slide sets. The Guides and the full report, with references for included and excluded studies, are available at the Effective Health Care Program Web site (
Reference:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness
Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

11. Traumatic Brain Injury and Depression Evidence Report: Key Questions 1–3
KQ1. What is the prevalence of depression after TBI, and does the area of the brain injured, the severity of the injury, the mechanism or context of injury, or time to recognition of the TBI or other patient factors influence the probability of developing clinical depression?
KQ2. When should patients who suffer TBI be screened for depression, with what tools, and in what setting?
KQ3. Among individuals with TBI and depression, what is the prevalence of concomitant psychiatric/behavioral conditions, including anxiety disorders, post-traumatic stress disorder (PTSD), substance abuse, and major psychiatric disorders?
Traumatic Brain Injury and Depression Evidence Report: Key Questions 1–3
In preparing the report on which this continuing medical education (CME) activity is based, the authors aimed to answer six Key Questions. Key Questions 1–3 are listed below:
KQ1. What is the prevalence of depression after TBI, and does the area of the brain injured, the severity of the injury, the mechanism or context of injury, or time to recognition of the TBI or other patient factors influence the probability of developing clinical depression?
KQ2. When should patients who suffer TBI be screened for depression, with what tools, and in what setting?
KQ3. Among individuals with TBI and depression, what is the prevalence of concomitant psychiatric/behavioral conditions, including anxiety disorders, post-traumatic stress disorder (PTSD), substance abuse, and major psychiatric disorders?
Reference:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness
Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

12. Traumatic Brain Injury and Depression Evidence Report: Key Question 4
KQ4. What are the outcomes (short- and long-term, including harm) of treatment for depression among TBI patients utilizing:
Psychotropic medications?
Individual/group psychotherapy?
Neuropsychological rehabilitation?
Community-based rehabilitation?
Complementary and alternative medicine?
Neuromodulation therapies?
Other therapies?
Traumatic Brain Injury and Depression Evidence Report: Key Question 4
In preparing the report on which this CME activity is based, the authors aimed to answer six Key Questions. Key Question 4 is listed below:
KQ4. What are the outcomes (short- and long-term, including harm) of treatment for depression among TBI patients utilizing:
Psychotropic medications?
Individual/group psychotherapy?
Neuropsychological rehabilitation?
Community-based rehabilitation?
Complementary and alternative medicine?
Neuromodulation therapies?
Other therapies?
Reference:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness
Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

13. Traumatic Brain Injury and Depression Evidence Report: Key Questions 5–6
KQ5. Where head-to-head comparisons are available, which treatment modalities are equivalent or superior with respect to benefits, short- and long-term risks, quality of life, or costs of care?
KQ6. Are the short- and long-term outcomes of treatment for depression after TBI modified by individual characteristics, such as age, pre-existing mental health status or medical conditions, functional status, and social support?
Traumatic Brain Injury and Depression Evidence Report: Key Questions 5–6
In preparing the report on which this CME activity is based, the authors aimed to answer six Key Questions. Key Questions 5–6 are listed below:
KQ5. Where head-to-head comparisons are available, which treatment modalities are equivalent or superior with respect to benefits, short- and long-term risks, quality of life, or costs of care?
KQ6. Are the short- and long-term outcomes of treatment for depression after TBI modified by individual characteristics, such as age, pre-existing mental health status or medical conditions, functional status, and social support?
Reference:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness
Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

14. Traumatic Brain Injury and Depression Evidence Report: Study Criteria
Category
Criteria
Study population
Adults aged ≥16 years old
Study settings and geography
Developed nations: United States, Canada, United Kingdom, Western Europe, Japan, Australia, New Zealand, Israel, South America
Publication languages
English only
Admissible evidence (study design and other criteria)
Admissible designs
Randomized controlled trials, cohorts with comparison, case-control, and case series (n ≥ 50)
Other criteria
Original research studies; provide sufficient detail on methods and results to enable use and adjustment of the data and results
Study participants that have been diagnosed with depression following a TBI received in adulthood
Studies must address one or more of the following for depression after TBI:
Treatment modality
Symptom management approach
Short- and long-term outcomes and quality of life
Relevant outcomes reported
Traumatic Brain Injury and Depression Evidence Report: Study Criteria
Controlled vocabulary terms were used to search five databases for publications to include in the evidence report. Reference lists of included articles were hand searched to identify additional citations. Studies were excluded if they: included fewer than 50 participants, included participants younger than 16 years of age, did not include an operational definition of depression, or were unable to be used to answer any Key Question. Penetrating head injuries were not considered in this report. The search identified 2,015 articles. Of these, 115 articles were included in the review, representing 81 distinct populations, with 112 articles pertaining to KQ1, 113 to KQ2, 9 to KQ3, 2 to KQ4, and none identified for KQ5 or KQ6.
Reference:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
TBI = traumatic brain injury
Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness, Review No AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

15. Strength of Evidence Ratings
The strength of evidence is classified into four broad ratings:
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 effect and may change the estimate.
Low
Low confidence that the evidence reflects the true effect. Further research is likely to change the confidence in the estimate of effect and is likely to change the estimate.
Insufficient
Signifies that evidence is either unavailable or does not permit a conclusion.
Strength of Evidence Ratings Throughout this slide set, strength of evidence ratings are assigned to findings of the report. Strength of evidence is typically assigned to reviews of medical treatments after assessing four domains: risk of bias, consistency, directness, and precision. Although these categories were developed for assessing the strength of treatment studies, the domains apply also to studies of prevalence and screening. Available evidence for each Key Question was assessed for each of these four domains; the domains were combined qualitatively to develop the strength of evidence for each Key Question.
References:
Guyatt GH, Oxman AD, Vist GE, et al., for the GRADE Working Group. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336:924-6.
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;63:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
Guyatt GH, et al. BMJ 2008;336:924-6; Owens DK, et al. J Clin Epidemiol 2010;63:513-23;
Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness
Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

16. Key Question 1 — Prevalence and Incidence of Depression in Traumatic Brain Injury
Regardless of the time since injury, the weighted average of the prevalence of depression secondary to TBI was 31%.a Strength of Evidence: Moderate
Evidence suggests that depression can occur after all forms and severities of TBI. Strength of Evidence: Low
Evidence is insufficient to advise patients with TBI or their health care providers about other risk factors for depression, including age, gender, area of brain injured, or mechanism of injury.
Key Question 1 — Prevalence and Incidence of Depression in Traumatic Brain Injury
Across all included populations, measures, and time frames, the aggregate prevalence of depression after TBI was 31.0% (range: 12.2–76.7%). This figure is derived from 112 publications based on 79 distinct study populations. Data are sparse to assess whether severity of injury influences risk of depression. Too few studies isolate a sufficient number of patients with mild TBI to compare to those with moderate and/or severe injuries to make valid severity-based estimates of prevalence. Likewise, stratification of prevalence by explanatory factors such as age, gender, area of brain injured, or mechanism of injury is not possible within the current body of literature.
Reference:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
aRange of prevalence across all populations, measures, and time frames:
12.2–76.7%.
Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness
Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

17. Key Question 2 — Screening for Depression After Traumatic Brain Injury
Timing: Depression in patients with a history of TBI occurs across all time frames; thus, no single optimal time frame for screening can be determined. Strength of Evidence: Low
Tools: Evidence is insufficient to determine optimal tools to screen patients with TBI for depression.
Key Question 2 — Screening for Depression After Traumatic Brain Injury
Key Question 2 aimed to identify the timing of screening for depression, which screening tools to use, and the optimal setting for screening to occur. No distinct trend was observed to suggest a peak time of enhanced risk or a related priority window for screening. Prevalence of depression is higher in all time frames than would be expected from population-based estimates. No evidence provides a basis for targeting screening to one time frame over another. Because of this, it may be advisable to screen frequently until evidence becomes available to better target timing of evaluations or to confirm that risk is elevated and stays elevated relative to the general population. Overall, the quality of studies that compare tools is poor. Thus, there is insufficient evidence on which to base conclusions about selection of screening methods. The evidence is also insufficient to determine whether tools for detecting depression that have been validated in other populations appropriately identify individuals with depression after a TBI.
Reference:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness
Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

18. Key Question 3 — Prevalence of Concomitant Psychiatric Conditions
Coexisting psychiatric conditions are common among depressed patients with a history of TBI.
The evidence available does not permit conclusions to be made about whether these comorbid conditions resulted from the TBI or were pre-existent.
Anxiety disorders including general anxiety disorder, PTSD, panic disorder, obsessive-compulsive disorder, and specific phobias were the most commonly reported coexisting conditions. Strength of Evidence: Low
Key Question 3 — Prevalence of Concomitant Psychiatric Conditions
Concomitant psychiatric conditions that were included for review were: anxiety disorders, substance abuse, irritability/aggression, and any other disorders named as axis I or axis II disorders in the Diagnostic and Statistical Manual for Mental Disorders. The included studies reported relatively high rates of concomitant psychiatric conditions (8–93% of depressed participants had some concomitant condition), depending on the particular psychiatric condition and the study population and design. However, because few studies presented these data separately for the depressed and nondepressed groups, few conclusions related specifically to this Key Question can be drawn. Anxiety disorders—including general anxiety disorders, PTSD, panic disorder, obsessive-compulsive disorder, and specific phobias—were the most commonly reported coexisting conditions. Most studies grouped these conditions together and reported the overall prevalence of any anxiety disorder (31–61% of study participants in four published studies).
References:
American Psychiatric Association. Diagnostic and statistical manual for mental disorders. 4th ed. Text revision. Arlington, VA: American Psychiatric Association; 2000.
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
American Psychiatric Association. Diagnostic and statistical manual for mental disorders. 4th ed. Text revision. 2000; Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

19. Key Questions 4 and 5 — Outcomes and Comparisons of Treatments for Depression After Traumatic Brain Injury
Evidence is insufficient to determine optimal treatment approaches for depression among patients who have a history of TBI.
Only two studies were identified that specifically addressed outcomes of a treatment intervention for individuals diagnosed with depression after TBI: one double-blind placebo-controlled trial and one open-label case series.
No head-to-head studies of treatments for depression after TBI were identified.
Key Questions 4 and 5 — Outcomes and Comparisons of Treatments for Depression After Traumatic Brain Injury
To understand the treatment options for patients with TBI and subsequent depression, the authors of this report sought publications that clearly documented the intervention, duration, and response to treatment. Using this approach, only two publications were identified that specifically addressed outcomes among individuals who were diagnosed with depression, had a history of TBI, and were treated with a selective serotonin reuptake inhibitor. The first was a U.S. randomized, placebo-controlled clinical trial; the second was a Canadian open-label case series. There were no head-to-head studies of treatments for depression after TBI on which to base conclusions about effectiveness.
Reference:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness
Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

20. Key Question 6 — Modifiers of Outcomes of Treatment
Evidence is insufficient to permit any conclusions about whether short- and long-term outcomes of treatment for depression after TBI are modified by individual patient characteristics.
Key Question 6 — Modifiers of Outcomes of Treatment
There were no studies that addressed Key Question 6. Therefore, no information is available on whether short- and long-term outcomes of treatment for depression after TBI are modified by individual patient characteristics.
Reference:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness
Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

21. Conclusions (1 of 2)
Patients with a history of TBI are at an increased risk for depression.
Increased prevalence of depression is observed at multiple time points after injury, ranging from shortly after injury to later.
Because the risk of depression after TBI remains high over an extended period, continued screening over time may be warranted.
Conclusions (1 of 2)
Patients with a history of TBI are at an increased risk for depression. Increased prevalence of depression is observed at multiple time points after injury, ranging from early to late. Because the risk of depression after TBI remains high over an extended period, continued screening over time may be warranted. There is a general lack of studies that make explicit comparisons of these concerns and are designed to specifically address issues related to screening for TBI after depression.
Reference:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness
Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

22. Conclusions (2 of 2)
The severity of a TBI has not been established as an accurate predictor of depression, suggesting the need for vigilance across all severities of TBI until more evidence is available.
While evidence exists for treatment of depression in the general population, studies involving individuals who have sustained TBI are insufficient to guide treatment for this specific population.
Conclusions (2 of 2)
Based on the available evidence, the severity of the brain injury is not an accurate predictor of depression, suggesting the need for vigilance across all severities of TBI. While evidence exists for treatment of depression in the general population, studies involving individuals who have sustained TBI are insufficient to guide treatment for this specific population.
Reference:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness
Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

23. What To Discuss With Your Patients
The prevalence of depression for patients with a history of TBI and the need for continued screening and communication concerning emerging symptoms.
Common symptoms of depression.
Association of depression with concomitant psychological conditions such as general anxiety disorder, PTSD, and panic disorder.
Adverse effects of antidepressants and possible drug interactions.
What To Discuss With Your Patients
The prevalence of depression and other concomitant psychological conditions for patients with a history of TBI and the need for continued screening and communication concerning emerging symptoms.
Common symptoms of depression, general anxiety disorder, PTSD, and panic disorder.
Possible drug interactions between antidepressants and other medications, as well as common adverse effects of antidepressants.
Reference:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness
Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

24. Future Research Needs (1 of 2)
Additional research on treatment options for patients with depression after TBI is a priority.
Studies are needed to compare the effectiveness of diagnostic approaches and timing and tools for screening.
Additional research is also needed to determine whether patient factors such as area of the brain injured, severity of the injury, mechanism of injury, age, and gender are predispositions for depression in patients with TBI.
Future Research Needs (1 of 2)
Five of the six Key Questions for this Comparative Effectiveness Review could not be adequately answered with existing literature, and the question about prevalence was only partially satisfied. The Key Questions were derived with expert and stakeholder input to define core knowledge for which we should have information. The questions themselves can serve as an outline for critical areas in which knowledge is insufficient. Lack of studies to assess how best to identify and treat depression after TBI is a cause for concern. High-quality research is warranted across the spectrum of study designs and aims.
Reference:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

25. Future Research Needs (2 of 2)
Future research studies should be randomized, use approaches that are clinically feasible, employ a comparison or control group where appropriate, and ensure comparability of treatment groups.
Studies pertaining to long-term outcomes and results of depression treatment in patients with TBI are needed to facilitate further comparison of the safety and effectiveness of treatments for TBI-induced depression.
Consensus is needed on outcomes that are important to both clinicians and patients to ensure consistency and comparability across future studies.
Future Research Needs (2 of 2)
Five of the six Key Questions for this Comparative Effectiveness Review could not be adequately answered with existing literature, and the question about prevalence was only partially satisfied. The Key Questions were derived with expert and stakeholder input to define core knowledge for which we should have information. The questions themselves can serve as an outline for critical areas in which knowledge is insufficient. Lack of studies to assess how best to identify and treat depression after TBI is a cause for concern. High-quality research is warranted across the spectrum of study designs and aims.
Reference:
Guillamondegui OD, Montgomery SA, Phibbs FT, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25 (Prepared by Vanderbilt Evidence-based Practice Center under Contract No I). Rockville, MD: Agency for Healthcare Research and Quality; March AHRQ Publication No. 11-EHC017-EF.
Available at:
Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.