1. Traumatic Brain Injury and Depression Prepared for: Agency for Healthcare Research and Quality (AHRQ) www.ahrq.gov

2.  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

3.  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. Background: Traumatic Brain Injury Langlois JA, et al. J Head Trauma Rehabil 2006;21:375-8; Okie S. N Engl J Med 2005;352:2043-7. 28% 20% 20% 19% 11% 22% Falls Motor-vehicle crashes Being struck by an object Assault Other

4.  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) 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.  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) Crooks CY, Zumsteg JM, Bell KR. Traumatic brain injury: a review of practice management and recent advances. Phys Med Rehabil Clin N Am 2007;18:681-710, 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.  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 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.  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 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.  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 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. 10-05143-EF-1. December 2009.

9.  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 Treatment Options for Depression Examined in the Systematic Review 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.  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 AHRQ Evidence Report Development and This CME Activity 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.  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 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.  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 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.  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 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 TBI = traumatic brain injury Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness, Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.

15.  The strength of evidence is classified into four broad ratings: Strength of Evidence Ratings 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.  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 a Range 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.  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 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.  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 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.  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 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.  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 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.  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) 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.  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) 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.  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 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.  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) 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 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) Guillamondegui OD, et al. Traumatic Brain Injury and Depression. Comparative Effectiveness Review No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF. March 2011.