Traumatic Brain Injury and Depression

1
Traumatic Brain Injury and Depression

• Prepared for
• Agency for Healthcare Research and Quality (AHRQ)
• www.ahrq.gov

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.

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.

Langlois JA, et al. J Head Trauma Rehabil
200621375-8 Okie S. N Engl J Med
20053522043-7.
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.

Faul M, et al. Traumatic brain injury in the
United States emergency department visits,
hospitalizations, and deaths 20022006. 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.

Crooks CY, Zumsteg JM, Bell KR. Traumatic brain
injury a review of practice management and
recent advances. Phys Med Rehabil Clin N Am
200718681-710, vi Faul M, et al. Traumatic
brain injury in the United States emergency
department visits, hospitalizations, and deaths
20022006. 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.

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 2628161-41.
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.

American Psychiatric Association. Diagnostic and
statistical manual for mental disorders. 4th ed.
Text revision. 2000 Busch CR, Alpern HP.
Neuropsychol Rev 1998895-108 Gordon WA, et al.
Am J Phys med Rehabil 200685343-82 Holsinger
T, et al. Arch Gen Psychiatry 20025917-22
Jorge RE, et al. J Neuropsychiatry Clin Neurosci
19935369-74 Kim E, et al. J Neuropsychiatry
Clin Neurosci 200719106-27 ODonnell ML, et
al. Am J Psychiatry 2004161507-14 Varney NR,
et al. Neuropsychology 198717-9.
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.

OConnor 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
Treatment Options for DepressionExamined in the
Systematic Review

• Psychotropic medications
• Selective serotonin reuptake inhibitors
• Serotonin and norepinephrine reuptake inhibitors
• Tricyclic antidepressants
• Monoamine oxidase inhibitors
• NonFDA-approved uses of other medications
• Psychotherapy
• Neuropsychological rehabilitation
• Community-based rehabilitation
• Complementary and alternative medicine
• Neuromodulation therapies

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 Developmentand 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.

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 DepressionEvidence
Report Key Questions 13

• 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?

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 DepressionEvidence
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?

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 DepressionEvidence
Report Key Questions 56

• 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?

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
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-E
F. 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.
Guyatt GH, et al. BMJ 2008336924-6 Owens DK,
et al. J Clin Epidemiol 201063513-23
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.

aRange of prevalence across all populations,
measures, and time frames 12.276.7.
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.

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 ofConcomitant
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

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.

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 ofOutcomes 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.

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.

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.

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.

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.

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.

Guillamondegui OD, et al. Traumatic Brain Injury
and Depression. Comparative Effectiveness Review
No. 25. AHRQ Publication No. 11-EHC017-EF017-1-EF
. March 2011.