Transcript Examples of Functional Neuroanatomy

Psychiatric Problems Following TBI
Jesse R. Fann, MD, MPH
Departments of Psychiatry and
Behavioral Sciences, Rehabilitation
Medicine, & Epidemiology
University of Washington
Seattle, Washington
Domains of TBI
• Neurobiological Injury
–Consequences of direct injury to brain
• Traumatic Event
–Risk for Post-traumatic Stress Disorder,
Depression
• Chronic Medical Illness
–May lead to long-term symptoms & disability
TBI as Neurobiological Injury
• Primary effects of TBI
– Contusions, diffuse axonal injury
• Secondary effects of TBI
– Hematomas, edema, hydrocephalus,
increased intracranial pressure,
infection, hypoxia, neurotoxicity,
inflammation
• Can affect mood modulating systems
including serotonin, norepinephrine,
dopamine, acetylcholine, and GABA
(Hamm et al 2000; Hayes & Dixon 1994)
Non-penetrating TBI
Diffuse Axonal Injury
Contusion
Subdural Hemorrhage
Taber et al 2006
Examples of Neuropsychiatric Syndromes
Associated with Neuroanatomical Lesions
• Leteral orbital pre-frontal cortex
– Irritability
- Impulsivity
– Mood lability
- Mania
• Anterior cingulate pre-frontal cortex
– Apathy
- Akinetic mutism
• Dorsolateral pre-frontal cortex
– Poor memory search
- Poor set-shifting / maintenance
• Temporal Lobe
– Memory impairment
- Mood lability
– Psychosis
- Aggression
• Hypothalamus
– Sexual behavior
- Aggression
Mayberg et al, J Neuropsychiatry Clin Neurosci
TBI as Traumatic Event
• PTSD Prevalence: 11-27% *
– Possibly more prevalent in mild TBI
– Mediated by implicit memory or conditioned fear
response in amnestic patients?
• PTSD Phenomenology: **
– Intrusive memories: 0-19%
– Emotional reactivity: 96%
– Intrusive memories, nightmares, emotional reactivity
had highest predictive power
• Anxiety often comorbid with / prolongs depression
* Warden 1997, Bryant 1995, Flesher 2001, Bombardier 2006
** Warden et al 1997, Bryant et al 2000
Psychiatric Illness in Adult HMO Enrollees
(N=939 with TBI, 2817 controls)
Psy chiatric Illness by TBI*
Predicted Cumulative Incidence
0.90
0.80
0.70
0.60
0.50
0.40
0.30
0.20
0.10
0.00
none
mild
mod./severe
No Prior Psychiatric Illness
6
12 18 24 30 36
Prior Psychiatric Illness
Month
6
12 18 24 30 36
* Predicted proportions for a women of age 40-44 with median index month (6), median log cost and no comorbid injuries
Fann et al. Arch Gen Psychiatry 2004; 61:53-61
0.90
0.80
0.70
0.60
0.50
0.40
0.30
0.20
0.10
0.00
Psychiatric Disorder & MTBI
20
18
16
14
12
10
8
6
4
2
0
MTBI
No TBI
MDD
GAD
Agora
PTSD
Social Ph
Panic
Bryant et al., Am J Psychiatry, in press
Neuropsychiatric Sequelae
•
•
•
•
•
•
•
•
Delirium
Depression
Mania
Anxiety
Psychosis
Cognitive Impairment
Aggression, Agitation, Impulsivity
Insomnia
Examples of Neuropsychiatric Syndromes
Associated with Neuroanatomical Lesions
• Leteral orbital pre-frontal cortex
– Irritability
- Impulsivity
– Mood lability
- Mania
• Anterior cingulate pre-frontal cortex
– Apathy
- Akinetic mutism
• Dorsolateral pre-frontal cortex
– Poor memory search
- Poor set-shifting / maintenance
• Temporal Lobe
– Memory impairment
- Mood lability
– Psychosis
- Aggression
• Hypothalamus
– Sexual behavior
- Aggression
Neuropsychiatric Evaluation and
Treatment: Etiologies
Psychiatric
Premorbid
Psych disorders & sxs.
Personality traits
Coping styles
Substance Abuse
Medication side effects
& interactions
Psychodynamic signif.
of neurologic illness
Family psych. history
Neurologic/Medical
Social
Neurologic illness
Lesion location, size,
pathophysiology
Other medical illness
Other indirect sequelae
(e.g., pain, sleep disturb)
Medication side effects
& interactions
Social, family, vocation
Rehabilitation situation
and stressors
Functional impairment
Medicolegal
Roy-Byrne P, Fann JR. APA Textbook of Neuropsychiatry, 1997
Neuropsychiatric Evaluation and
Treatment: Workup
Psychiatric
Neurologic/Medical
Psychiatric history &
Medical history and
examination
physical examination
Neuropsychological
Appropriate lab tests
testing
e.g., CBC, med blood
Psychodynamic signif. of
levels, CT/MRI, EEG
neuropsychiatric sxs.,
Medication allergies
disability and treatments
Social
Interview family, friends,
caregivers
Assess level of care &
supervision available
Assess rehab needs
& progress
Neuropsychiatric History
Psychiatric symptoms may not fit DSM-IV criteria
Focus on functional impairment
Document and rate symptoms (use validated instruments)
Assess pre-TBI personality, coping, psychiatric history
Talk with family, friends, caregivers
Explore circumstances of trauma
LOC, PTA, hospitalization, medical complications
Subtle symptoms - may fail to associate with trauma
How has life changed since TBI?
Thorough review of medical and psychiatric sxs.
Assess level of care and supervision available
Assess rehabilitation needs and progress
Neuropsychiatric Treatment
• Use Biopsychosocial Approach
• Treat maximum signs and symptoms with fewest
possible medications
• TBI patients more sensitive to side effects
START LOW, GO SLOW, BUT GO
• May still need maximum doses
• Therapeutic onset may be latent
• Some medications may lower seizure threshold
• Some medications may slow cognitive recovery
• Monitor and document outcomes
• Few randomized, controlled trials
Delirium
• Acute disturbance of consciousness, cognition
and/or perception
• Increased risk in patients with TBI
• Undiagnosed in 32-67% of patients
– Often missed in both inpatient and outpatient
settings
• Associated with 10-65% mortality
• Can lead to self-injurious behavior, decreased selfmanagement, caregiver management problems
• Associated with increased length of hospital stay
and increased risk of institutional placement
• Other terms used to denote delirium: acute
confusional state, intensive care unit (ICU)
psychosis, metabolic encephalopathy organic brain
syndrome, sundowning, toxic encephalopathy
Delirium
• Identify and correct underlying cause
– TBI increases a person’s vulnerability
– e.g., seizures, hydrocephalus, hygromas, hemorrhage, drug side effect or
interactions, endocrine (hypothalamic, pituitary dysfunction), metabolic
(e.g., sodium, glucose), infections
• Pharmacologic management
– Antipsychotics
» Haloperidol (e.g., IV), droperidol, risperidone, olanzapine, quetiapine
(taper 7 – 10 days after return to baseline)
– Benzodiazepines (combined with antipsychotics), alcohol or sedative
withdrawal
» lorazepam
• Minimize polypharmacy
• Medical management
– Frequent monitoring of safety, vital signs, mental status and physical
exams
– Maintain proper nutritional, electrolyte, and fluid balance
• Behavioral Management – safety, orientation, activation
Depression / Apathy
• Prevalence of major depression 44.3% *
– Assess pre-injury depression and alcohol use
– Use ‘inclusive’ diagnostic technique
– May occur acutely or post-acutely
– Not directly related to TBI severity
• Apathy alone - prevalence 10%
– disinterest, disengagement, inertia, lack of motivation,
lack of emotional responsivity
* van Reekum et al. J Neuropsychiatry Clin Neurosci 2000;12:316-327
DSM-IV Major Depressive Disorder (MDD)
1.
2.
3.
4.
5.
6.
7.
8.
9.
•
•
Depressed mood*
Loss of interest/pleasure*
Sleep disturbance
Poor energy
Motor change agitation or slowness
Weight/appetite change increase/decrease
Impaired concentration or indecision
Excessive worthlessness or guilt
Recurrent thoughts of death or suicide
At least one of the essential criteria* and a total of at
least 5 symptoms endorsed most of the day most days
for at least 2 weeks
Must cause clinically significant impairment
APA, Diagnostic & Statistical Manual of Mental Disorders, 4th ed, 2000
Transdiagnostic Symptoms
TBI
1.
2.
3.
4.
5.
6.
7.
8.
9.
Depressed mood
Anhedonia
Weight loss/gain
Insomnia/hypersomnia
Psychomotor changes
Fatigue
Worthlessness/guilt
Poor concentration
Thoughts of death/suicide
X
X
X
X
Patient Health Questionnaire - 9
Not
at all
Several
days
More
than
half the
days
Nearly
every
day
1. Little interest or pleasure in doing things
0
1
2
3
2. Feeling down, depressed, or hopeless
0
1
2
3
3. Trouble falling or staying asleep, or sleeping too much
0
1
2
3
4. Feeling tired or having little energy
0
1
2
3
5. Poor appetite or overeating
0
1
2
3
6. Feeling bad about yourself — or that you are a failure or have let
yourself or your family down
0
1
2
3
7. Trouble concentrating on things, such as reading the newspaper or
watching television
0
1
2
3
8. Moving or speaking so slowly that other people could have noticed?
Or the opposite — being so fidgety or restless that you have been
moving .around a lot more than usual
0
1
2
3
9. Thoughts that you would be better off dead or of hurting yourself in
some way
0
1
2
3
Over the last 2 weeks, how often have you been bothered by any of the
following problems?
Spitzer et al. JAMA 1999
Rates Of Major Depression After TBI
53%
N = 559
Point Prevalence of MDD
Range 21-31%, no trend
Cumulative Rate of MDD as a
Function of Depression History
73%*
69%*
41%
*P < .001; independent predictors after adjusting for all other variables
Rate of MDD by History of Lifetime
Alcohol Dependence
70%*
45%
*P < .001; independent predictor after adjusting for all other variables
Cumulative Rate of MDD by PTSD History
81%
51%
Univariate predictor, not significant after adjusting for other variables
Comorbidity of Anxiety and MDD
Cumulative Percent
100
90
MDD-
80
MDD+
70
60
54
50
40
27
30
20
10
1
6
0
Panic Disorder
Other Anxiety Disorder
Any comorbid anxiety disorder in MDD+ vs. MDD(60% vs. 7%; RR, 8.77; CI, 5.56-13.83)
Depression / Apathy
• Selective serotonin re-uptake inhibitors (SSRIs)
- sertraline
- citalopram
•
•
•
•
•
•
- paroxetine
- escitalopram
- fluoxetine
venlafaxine, duloxetine (may help with pain)
bupropion (may decrease seizure threshold)
nefazedone (may be too sedating, liver toxicity)
mirtazapine (may be too sedating)
Tricyclics: nortriptyline, desipramine (blood levels)
methylphenidate, dextroamphetamine
Electroconvulsive Therapy – consider less frequent,
nondominant unilateral
• Apathy: Dopaminergic agents - methylpyhenidate,
pemoline, bupropion, amantadine, bromocriptine,
Fann et al, J Neurotrauma 2009
modafinil
Number of Postconcussive
Symptoms
7
7
6
5
3.9
# of
symptoms
3.5
4
3
2.2
2
1
* p=.05
* p=.05
0
symptoms
*
All All
symptoms
*
Current Depression
Depressive symptoms excluded
Depressive
symptoms excluded
No current Depression
PCS – Depression Study
(Baseline and Week 8)
**
Headache
Dizziness
Blurred Vision
Improving
Worsening
Same
Bothered by Noise
Bothered by Light
Loss of Temper
**
Fatigue
Trouble Concentrating
*
*
Irritability
Memory Difficulties
Anxiety
*
Sleep Disturbance
*p<.05
**p<.01
0
2
4
6
8
10
12
14
16
Treatment options
• Antidepressant medications:
– Particularly for major depression and dysthymia
• Psychotherapy: for all forms of depression (esp. CBT)
– Pro: no side effects, may last longer (‘learning effect’), addresses
interpersonal / real life problems, flexible delivery options
– Con: may need to adapt for cognitive impairment, may cost more
and take longer to work, more time consuming, may not be as
effective for severe major depression
• Other psychosocial interventions (e.g., educational &
support groups)
• Support and watchful waiting
• Often optimal treatment with combination of
antidepressants and psychotherapy
Modifiable Risk Factors
Neurobiological
Factors
No Pleasant
Activities
Depression
Psychosocial
Adversity
Cognitive
Distortions
Sedentary Lifestyle
Life
Improvement
Following
Traumatic Brain Injury:
A Trial of Cognitive-Behavioral Therapy
for Depression after TBI
Jesse R. Fann, MD, MPH
Departments of Psychiatry & Behavioral
Sciences and Rehabilitation
Medicine
School of Medicine
Department of Epidemiology
School of Public Health
University of Washington
Charles H. Bombardier, PhD
Steven Vannoy, PhD
Peter Esselman, MD
Kathy Bell, MD
Nancy Temkin, PhD
University of Washington
Evette Ludman, PhD
Group Health Research Inst
Reason
Slowed
information
processing &
responding
Impaired
attention &
concentration
Accommodations
Present information at slower rate
Allow client more time to respond
Provide written summary of session beforehand
Minimize environmental stimulation and distractions during session
Focus on one topic at a time, Use shorter sessions
Avoid need for multi-tasking e.g., no note taking while listening
Impaired learning Provide written summary of session (patient workbook)
& recall
Assign simple written homework
Provide written educational materials or workbook
Plan additional practice of CBT skills within session (over-learn skills)
Impaired verbal
abilities
Impaired
initiation &
generalization
Impaired
motivation
Minimize emphasis on verbally mediated aspects of CBT
Emphasize behavioral activation and pleasant events scheduling
Include family or friend in treatment planning and homework
assignments
Provide 2 sessions devoted to generalization and relapse prevention at
end
Use motivational interviewing techniques to engage subjects in therapy
Provide care management activities aimed at return to work, school or
other meaningful roles and finding effective rehabilitation resources
Mania
• Prevalence of Bipolar Disorder 4.2% * after TBI
• Look for:
– elevated, expansive or irritable mood
– grandiosity
– decreased need for sleep
– pressured speech
– flight of ideas, distractability
– impuslivity
• High rate of irritability, “emotional incontinence”
• May be associated with epileptiform activity
• Potential interaction of genetic loading, right hemisphere
lesions, and anterior subcortical atrophy
* van Reekum et al. J Neuropsychiatry Clin Neurosci 2000;12:316-327
Mania
• Acute
– Benzodiazepines
– Antipsychotics
» olanzapine, risperidone, quetiapine, clozapine
– Anticonvulsants
» valproate
– Electroconvulsive Therapy
• Chronic
– valproate
– carbamazepine
– lamotrigine
– lithium carbonate (neurotoxicity)
– gabapentin, topiramate (adjunctive treatments)
Pseudobulbar Affect
A neurologic condition characterized by episodes of
crying or laughing that are sudden, frequent, and
involuntary
Occurs in patients with TBI, MS, ALS, stroke, and
certain other neurologic conditions
FDA-approved in 2011 – Nuedexta ®
Dextromethorphan (20mg) – modulates glutamate
+
Quinidine (10mg) – metabolic inhibitor
Anxiety Disorders
•
•
•
•
•
•
•
Adjustment Disorder
Posttraumatic Stress Disorder
Panic Disorder
Generalized Anxiety Disorder
Specific Phobia – e.g., medical procedures
Obsessive-Compulsive Disorder
Anxiety Disorder due to General Medical Condition (e.g.,
hypoxia, sepsis, pain)
• Substance-induced Anxiety Disorder
Rates of Anxiety Disorders (civilians)
GAD
PTSD
OCD
Panic
Phobias
24%
NA
NA
4%
2% Agoraphobia
8%
17%
14%
11%
3%
3%
2%
17%
14%
13.4%
13%
NA = Not Assessed.
Sample
50 patients diagnosed with TBI seen at a
rehabilitation clinic -mean 32.5 months
post injury
Fann et al.,
1995
7%
100 patients with TBI - mean 7.6 years
post injury
Hibbard et al.,
1998
9%
1%
100 patients hospitalized for TBI - 1 year
post injury
Deb et al., 1999
1%
6%
7%
Specific Phobia
6%
Social Phobia
1% Agorophobia
100 patients hospitalized for TBI assessed 0.5 - 5.5 years post injury
WhelanGoodinson et
al., 2009
4%
7.5%
12.8%
Agoraphobia
9% Social Phobia
817 patients hospitalized for traumatic
injury (40% TBI) - assessed 1 year post
injury
Bryant et al.,
2010
Anxiety
• Often comorbid with and prolongs course of
depression in TBI
• Posttraumatic Stress Disorder: Prevalence 14.1% *
– Reexperience, Avoidance, Hyperarousal
– > 1 month, causes significant distress or impairment
– Possibly more prevalent in mild TBI
• Panic Disorder: Prevalence 9.2% *
• Generalized Anxiety Disorder: Prevalence 9.1% *
• Obsessive-Compulsive Disorder: Prevalence 6.4% *
* van Reekum et al. J Neuropsychiatry Clin Neurosci 2000;12:316-327
Adjustment Disorders
• Clinically significant symptoms of depressed mood,
anxiety, or both
• Occurring within 3 months in response to an
identifiable stressor(s); once the stressor has
terminated, the symptoms do not persist for more
than an additional 6 months
• Causing marked distress that is in excess of what
would be expected from exposure to the stressor
and significant impairment in social or occupational
(academic) functioning
• The stress-related disturbance does not represent
bereavement or meet the criteria for another Axis I
disorder.
PTSD Criteria
CLUSTER A: Stressor
A. Experience/witness threat
B. Respond with fear/helplessness*
CLUSTER B: Reexperiencing
At least 1 of:
• A. Intrusive memories*
• B. Nightmares*
• C. Flashbacks*
• D. Psychological distress to reminders*
• E. Physiological reactivity to reminders*
PTSD Criteria (cont’d)
CLUSTER C: Avoidance
At least 3 of:
A. Avoid thoughts, feelings
B. Avoid places, activities
----------------------------------------C. Dissociative amnesia*
D. Diminished interest
E. Detachment from others
F. Restricted affect*
G. Foreshortened future
CLUSTER D: Arousal
At
A.
B.
C.
D.
least 2 of:
Sleep disturbance*
Anger*
Concentration difficulties*
Hypervigilence
PTSD Criteria (cont’d)
CLUSTER E: Symptoms last at least 1 month
CLUSTER F: Causes impairment
CLUSTER H: Not due to medical condition or
substance abuse*
PTSD Risk Factors
Trauma
• Level of threat
• Exposure to grotesque
events
• Fatality/injuries
• Uncontrollable event
• Duration of disaster
Peri-Trauma
• Panic
• Dissociation
• Catastrophic appraisals
Post-Truama
• Low social support
• Coping style
• Community reaction
• Ongoing stressors
• Comorbidity
• Secondary symptoms
Psychiatric Disorder & Prior
Sleep Problems
Bryant et al., Sleep, in press
Role of Trauma Memories
• One study reported that confidence in
memory for traumatic experience
inversely related to PTSD development
Gil et al., (2007), Am J Psychiatry
Interface of PTSD & Persistent PCS
Stein & McAllister, AJP 2009
Brain regions implicated in PTSD
and vulnerable to TBI
Implications
• Mild TBI patients need to be monitored
for stress reactions
• Do not confuse effects of Mild TBI with
effects of stress
• Interaction of the two factors suggest
that optimal intervention for PCS will
focus on stress reactions
Panic Attack
• Intense fear or discomfort
• At least 4 symptoms peak in 10 min
–
–
–
–
–
–
–
–
–
–
–
–
–
palpitations, pounding heart, or accelerated heart rate
chest pain or discomfort
shortness of breath or smothering
feeling of choking
feeling dizzy, unsteady, light-headed, or faint
paresthesias (numbness or tingling sensations)
chills or hot flashes
trembling or shaking
sweating
derealization or depersonalization
fear of losing control or going crazy
fear of dying
nausea or abdominal distress
Panic Disorder
• Recurrent unexpected panic attacks for
1 month (or more
• either persistent concern about having
additional attacks or worry about the
implications of the attack or its
consequences (eg, losing control, having a
heart attack, “going crazy”) or a significant
change in behavior related to the attacks.
Generalized Anxiety Disorder
A. Excessive anxiety and worry, occurring more days than not ,
for at least 6 months, about a number of events of activities
B. Difficult to control the worry
C. Associated with 3 or more symptoms (some present more
days than not for at least 6 months)
–
–
–
–
–
–
Restless, keeyed up, or on edge
Easily fatigued
Difficult concentrating or mind going blank
Irritable
Muscle tension
Difficulty falling or staying asleep, or restless sleep
D. Focus of anxiety / worry not confined to features of another
Axis I disorder
E. Clinically significant distress or impairment
F. Not due to substance or general medical condition and does
not occur exclusively during a Mood, Psychotic, or Pervasive
Dev Disorder
Anxiety
Medications
• Benzodiazepines: use lower doses (~50% typical dose)
– e.g., clonazepam, lorazepam, alprazolam
– Watch for cognitive impairment, disinhibition, dependence
• Buspirone (for Generalized Anxiety Disorder)
• Antidepressants
– SSRIs, venlafaxine, nefazedone, mirtazapine, TCAs
• Beta-blockers, verapamil, clonidine
• Anticonvulsants: Valproate & gabapentin have some
anxiolytic effects
Psychosocial
– Individual (CBT, Behavioral Activation), couples, family, group
Psychosis
• Hallucinations, delusions, thought disorder
• Immediate or latent onset
• Symptoms may resemble schizophrenia:
prevalence 0.7%* in TBI
• Schizophrenics have increased risk of TBI predating psychosis
• Patients developing schizophrenic-like
psychosis over 15-20 years is 0.7-9.8%
• Look for epileptiform activity and temporal lobe
lesions
• Treatment: Antipsychotic medications (referral)
* van Reekum et al. J Neuropsychiatry Clin Neurosci 2000;12:316-327
Psychosis
• Antipsychotics
– First generation: e.g. haloperidol, chlorpromazine (seizures)
– Second generation: e.g., risperidone
– Third generation: e.g., olanzapine, quetiapine, ziprasidone,
aripiprazole, clozapine (seizures)
• Start with low doses (e.g., Risperidone 0.5mg qHS)
• TBI pts have high risk of anticholinergic and
extrapyramidal side effects
• May cause QTc prolongation, increased sudden death
in elderly
• Use sparingly - may impede neuronal recovery acutely
(from animal data)
Cognitive Impairment
• Common problems after TBI
– Concentration and attention
– Memory
– Speed of information processing
– Mental flexibility
– Executive functioning
– Neurolinguistic
• Association with Alzheimer’s Disease suggested
• Cognitive Rehabilitaiton may help
• May be associated with other psychiatric
syndromes (e.g., depression, anxiety, psychosis)
– treating these may improve cognition
Cognitive Impairment
May improve recovery
• Stimulants
– methylphenidate, dextroamphetamine, caffeine
• Nonstimulant dopamine enhancers
– amantadine, bromocriptine, pramipexole, L-dopa/carbidopa
• Acetylcholinesterase inhibitors
– physostigmine, donepezil, rivastigmine, galantamine
• Antidepressants
– sertraline, fluoxetine, milnacipran (SNRI)
• Others
– CDP Choline, gangliosides, pergolide, selegiline, apomorphine,
phenylpropanolamine, naltrexone, atomoxetine, vasopressin
Writer & Schillerstrom, J Neuropsychiatry Clin Neurosci 2009
Cognitive Impairment
May impede recovery
haloperidol
phenothiazines
prazosin
clonidine
phenoxybenzamine
GABAergic agents
benzodiazepines
Phenytoin
carbamazepine
phenobarbital
idazoxan
Aggression, Irritability, Impulsivity
•
•
•
•
Up to 70% within 1 year of TBI
May last over 10-15 years
Interview family and caregivers, if possible
Characteristic features
– Reactive
– Non-reflective
– Non-purposeful
- Explosive
- Periodic
- Ego-dystonic
• Treat other underlying etiologies (e.g., bipolar)
• Treatment: Medications and behavioral
interventions
Pilot study of sertraline (N=15)
Brief Anger / Aggression
Questionnaire (BAAQ)
10
9
8
7
6
5
4
3
2
1
0
p=.05
baseline
Fann et al. Psychosomatics 2001; 42:48-54
week 8
Aggression, Agitation, Impulsivity
(none FDA approved for this indication)
• Acute
Antipsychotics (e.g., Quetiapine 25-50mg bid)
Benzodiazepines (e.g., Clonazepam 0.5mg bid)
• Chronic
Beta-blockers (e.g. propranolol – may need up to 200mg/d
in some cases, pindolol, nadolol)
valproate, carbamazepine, gabapentin
Lithium (narrow therapeutic window)
buspirone
Serotonergic antidepressants (e.g., SSRIs, trazodone)
tricyclic antidepressants (e.g., nortriptyline, desipramine)
Antipsychotics (esp. second and third generation)
amantadine, bromocriptine, bupropion
clonidine, methylphenidate, naltrexone, estrogen
Non-Pharmacologic Interventions
• Behavioral Modification
– Based on operant learning principles, e.g., managing environmental
contingencies
» Require high degree of environmental control & consistency;
therefore, difficult in outpatient settings
» Typically amplify or suppress behaviors, rathern than teach new
responses to triggers or antecedents
• Psycho-educational (small RCT, N=16)
– Based on Novaco’s Stress Innoculation Training (SIT)
» Based on CBT principles
» Heighten awareness of cognitive distortions that fuel inappropriate
emotional reactions
» Teach more adaptive responses
» May be difficult for people with cognitive impairment
• Anger Self-Management Training (ASMT) – Moss + UW Study
– Based on Self-Care and Problem-Solving Training
– Improves awareness and ability to attend to anger signals
– Establishes new, constructive habits for coping with threat
Treatment: Insomnia
• Treat underlying etiology (e.g., pain, anxiety, depression,
sleep apnea)
• Emphasize sleep hygiene, Cognitive Behavioral Therapy
• Medications often dependence-forming
• Benzodiazepines (fast-acting)
– lorazepam (Ativan), temazepam (Restoril), alprazolam
(Xanax)
• Non-benzodiazepines
– short-acting: zolpidem (Ambien), zaleplon (Sonata),
ramelteon (Rozerem)
– Longer acting: zolpidem CR (Ambien CR), Lunesta
• Antihistamines: diphenhydramine (Benadryl)
• Antidepressants: trazodone (Desyrel), amitriptyline
Sleep Hygiene Principles
Sleep/wake principles
• Maintain habitual bed and rise times
• Restrict time in bed
• Explore the usefulness / detriment of napping
Environmental principles
• Ensure bedroom is sufficiently dark
• Minimize disturbing noise (use earplugs, if needed)
• Ensure bedding, temperature and airflow are consistent with quality
sleep
• Ensure a nightlight does not illuminate the eyes while in bed
• Eliminate or place bedroom clocks so that they cannot be viewed
from bed
• Eliminate other distractions, e.g., pets
Diet and drug use principles
• Avoid rich food late in the evening
• Explore the usefulness of a late bedtime snack
– Try snacking on foods that promote sleep
» E.g., milk, bananas, turkey, cheese, peanut butter
• Avoid caffeine, alcohol and tobacco, esp. in the evenings
• Be aware that OTC and Rx medications may adversely affect sleep
Proposed Model
TBI Severity
+,-
Cognition
+
TBI
+/-
Neurosychiatric
Symptoms
+/-
Postconcussive
Symptoms
Psychiatric
Vulnerability
Functioning/
QOL
Health Care
Utilization
“The significant problems we face
cannot be solved at the same level
of thinking we were at when we
created them”
Albert Einstein