Download Post-traumatic Stress Disorder (PTSD) Overview

Posttraumatic syndrome
Surakrant Yutthakasemsunt , M.D
Khonkaen Regional Hospital
Khonkaen ,Thailand
23 June 2006
Consideration
• Wastebasket term
• No unique clinical diagnostic criteria
• Controversy in etiological details
• Inconsistency clinical presentation
• Limit of study methodological problems
Related Terms
•
•
•
•
•
Posttraumatic syndrome:PTS
Posttraumatic stress disorder:PTSD
Posttraumatic stress syndrome
Posttraumatic neck syndrome
Post-Concussive Syndrome:PCS
Posttraumatic stress disorder
• Shell shock
• Battle fatigue
• Accident neurosis
• Post rape syndrome
Neurobiological Changes after TBI
– cortical contusions (mostly in severe TBI)
• results in a loss of function served by that area
– white matter lesions
• results in interruption of information processing between cortical
areas
– diffuse axonal injury
• results in slowed and inefficient information processing
• disproportionately affects glutamatergic and cholinergic projections
– results in problems with attention, memory, and various aspects of
frontally-mediated cognition (ie, working memory, executive function)
• may affect serotonergic systems
• dysfunction in these systems may secondarily affect the efficiency of
function in dopaminergic or noradrenergic systems
Clinical Features
• Somatic-organic or physical problems
• Psychosocial or neuropsychiatry
problems
• Cognitive problems
Mixed and fluctuating symptom features over time
especially neuropsychiatry problems
Patterns of Post-Concussive Symptoms
Filter Effects of CNS Injury
• What does depression look like in
someone who is non-verbal?
• What does manic hyperactivity look
like in someone with quadriplegia?
• How do hallucinations and delusions
present in someone who cannot
describe them?
Vulnerability to Side Effects
• Neuropsychiatric patients show
increased frequency & severity of side
effects to most psychotropics
• Can manifest as worsening of
neurological problems (tremor,
cognition, slowing, etc.)
Medications and Drugs
Associated with Aggression
• Alcohol: intoxication and withdrawal
• Hypnotic and anxiolytics: intoxication and withdrawal
• Analgesics (narcotics): intoxication and withdrawal
• Steroids (prednisone, cortisone, and anabolic steroids)
• Antidepressants: especially during initial phases of Rx
• Amphetamines and cocaine
• Antipsychotics: secondary to akathisia
• Anticholinergic drugs: delirium
• Quinolone antibiotics?
General Principles
• Drug Impact on Cognition
• Memory – Benzodiazepines,
antidepressants (anticholinergic effects)
• Attention – Benzodiazepines,
neuroleptics
• Speed of Information Processing –
Benzodiazepines, neuroleptics, others
• Thus the very areas most affected by TBI
Neurotransmitter Dysfunction after TBI
• Many neurotransmitters are involved in the
regulation of cognition, emotion, behavior, and
physical/motor function
• Principal neurotransmitters in regulation of
frontal and frontotemporal functions include:
– dopamine
– norepinephrine
– serotonin
– acetylcholine
– glutamate
– gamma-aminobutyric acid (GABA)
Ways of Altering Synaptic
Content of Neurotransmitters
Synthesis
Storage
Release
Binding
Re-uptake
Metabolism
Dopamine Agonists
• A variety of agonists have been
shown effective in animal models and
are used clinically:
–Methylphenidate (and other stimulants)
–Amantadine
–Bromocriptine
–Bupropion
Alpha-2-Adrenergic Agonists
• Infusion of A2A agonists improves
WM function in primates and rodents
• guanfacine can improve WM in
healthy individuals and may improve
working memory after TBI
• Methylphenidate also has A2A agonist
properties
Cholinergic Augmentation
• Multiple studies demonstrate that cholinergic
augmentation, generally using one of several
cholinesterase inhibitors (e.g.,
physostigmine, donepezil) can improve TBIinduced attention and memory deficits even
in the late post-injury period (>1 year) in
some TBI survivors
– Taverni 1998; Whelan 2000; Cardenas 1994;
Arciniegas 2001
Prior to Treatment
• Accurate diagnosis is critical first step
• Know what you are treating before
treatment
• Are you treating the underlying
disorder, or the comorbid
psychopathology?
Neuropsychological Battery (Some)
•
Orientation
– Galvestone Orientation and Amnesia Test (GOAT)
•
Motor
– Grooved Pegboard test
•
Attention,Cognition processing Speed
– Wechsler Memory Scale-Revised Digit Span
– Symbol Digit Modality Test
•
Visual Scanning,Analysis and Construction
– Trailmaking Test
– Boston Visual Discrimination Test
– Wechsler Adult Intelligence Scale-Revised Block Design (WAIS-RBD)
•
Language
– Control Oral Word Association Test (COWAT)
– Multilingual Aphasia Examination Token Test
•
Memory
– Wechsler Memory Scale-Revised Logical Memory
– Rey Auditory Verbal Learning Test (RAVLT)
•
Problem Solving
– Wisconsin Card Sorting Test
Why learn about medications?
• Improves care
• Improves your clinical skills
• Fosters participation in treatment
• Facilitates holistic approach to care
Psychopharmacological Approach
• Clarify/simplify current regimen
• Clarify critical target symptoms to treat
• Target specific symptoms
Medication approaches
1. amelioration of specific somatic
symptoms (e.g., headache,
dizziness, sleep disturbances)
2. amelioration of psychobehavior
complications
3. augmentation of cognition
Dosage Considerations
Start lower
Go slower
Stop sooner
Psychopharmacological Issues
• At present, there are no FDA approved
treatments for cognitive, emotional, or
behavioral impairment due to TBI
• Pharmacotherapies are generally modeled
after those for patients with
phenomenologically similar but
etiologically distinct disorders (attentiondeficit hyperactivity disorder, Alzheimer’s
disease, etc.)
Physical Symptoms After Concussion
• Headache
• Fatigue
• Dizziness/ Dysequilibrium • Insomnia
• Aesthenia/ Weakness
• Anosmia
• Numbness/ Paresthesias • Photophobia
• Tinnitus/ Hearing ↓↓
• Hypersensitivity to sound
• Blurred Vision
Post-concussive Headache
• Musculoskeletal
–Myofascial
– Upper Cervical Spine
• Neurogenic
– Greater or Lesser Occipital Neuralgia
– Scalp Neuroma from laceration or
contusion
• Vascular
– Not very common (although more-so in
kids/predisposition)
--Overlap in receptive fields for upper cervical
dorsal horns and spinal tract of trigeminal nerve
• “Dysautonomic”
Treatment of Post-Concussive Headache
• Musculoskeletal: NSAIDs, Amitryptiline, TP
injection, PT, Manual Medicine
• Neurogenic: Injection, anticonvulsants,
Amitryptiline, counter-stimulants, PT, TENS,
Lidoderm patches
• Vascular: Abortive Rx, Preventative Rx
Post-Concussive “Dizziness”
Postural Instability
vs
Vestibular Dysfunction
(vertigo, nystagmus)
Post-Concussive Postural Instability
• Musculoskeletal
• Neurological
– Visual
– Proprioceptive
– Vestibular
– Integrative
Post-Concussive Vestibular Dysfunction
• Vertigo
• Gaze Instability
• Postural Control
Post-concussive Vestibular Problems
• Benign Paroxysmal Positional Vertigo
(habituates)
• Central Positional (will not habituate)
• Cervicogenic (habituates)
• Perilymphatic fistula (bed rest, surgery)
• Endolymphatic hydrops
– Betahistine, suppressants, surgery
• Unilateral Vestibular Loss
• Bilateral Vestibular loss
– head and neck are rigid, gaze unstable
Evaluation of Post-Concussive Dizziness
• Neuro-otology consult
• Imaging
• Electronystagmography (ENG)
• Caloric/rotary testing
• Posturography
Treatment of Post-concussive Dizziness
• Physical Therapy
– Habituation Exercises
– “Liberatory” Exercises (BPPV)
– Oculo-vestibular Exercises
• Behavioral
• Pharmacological
• Surgery
Pharmacological Treatment of
Post-Concussive Dizziness
•
•
•
•
Meclizine (Antivert)
Scopolamine (anticholinergics)
Benzodiazepines
Antihistamines
– Loratadine ?
All may impede “natural” recovery
and/or effectiveness of therapy
Emotional/Affective Symptoms
After Concussion
• Irritability
• Lability /inappropriate emotions (Mood change)
• Depression
• Anxiety/agitation
• Decreased libido
• Impulsive
Despite Diagnostic Challenges
• When behaviors change:
– New behaviors
– Change in frequency and intensity of previous
behaviors
• Have a high index of suspicion for the common
psychiatric disorders
Common Behavioral Syndromes
in the Injured Brain
• Depressive Syndromes
• Dyscontrol Syndromes
• Attention Deficit Syndromes
• Sleep Disorders
• Psychotic Syndromes
Psychiatric Disorders and TBI
• Disorders of thought content and thought
process complicate recovery from TBI
• Psychotic syndromes occur at rates greater
than those in general population
• Injury severity positively correlated with risk
• Even in absence of formal criteria,many with
TBI have psychotic symptoms
Other Links to Psychosis
• PTA
– resembles delirium in many respects
– Restlessness, fluctuating level of consciousness,
agitation.
– Hallucinations and delusions occur frequently
• Mood Disorders
– Depression
– Mania
• Seizure Disorders
Aggression and TBI
• Acute phase: 35% - 96% of patients exhibit
agitated behaviors
– 89 patients assessed during the first six months
after TBI, aggressive behavior found in 33.7% of
TBI patients, compared to 11.5% of patients with
multiple trauma but without TBI (Tateno et al)
• Recovery phase: 31% - 71% of patients with
severe TBI and 5% - 70% of patients with mild
TBI are agitated or irritable
• Irritability increases with more TBI’s
Characteristics of Aggression
After TBI
• Reactive: Triggered by modest or trivial stimuli
• Nonreflective: Usually does not involve
premeditation or planning
• Nonpurposeful: Aggression serves no obvious longterm aims or goals
• Explosive: Buildup is NOT gradual
• Periodic: Brief outbursts of rage and aggression,
punctuated by long periods of relative calm
• Ego-dystonic: After outbursts, patients are upset,
concerned, and/or embarrassed, as opposed to
blaming others or justifying behavior
Neuropathology of Aggression
• Hypothalamus
Orchestrates neuroendocrine response to sympathetic arousal
Monitors internal status
• Limbic system
Amygdala
Activates and/or suppresses hypothalamus
Input from neocortex
Temporal cortex
Associated with aggression on both ictal and interictal
status
• Frontal neocortex
Modulates limbic and hypothalamic activity
Associated with social and judgment aspects of aggression
Factors Associated with
Agitation in Brain Injury
Adverse
Environment
Psychosis
Medical
Illness
AGITATION
Aggression as
direct effect of
Brain Injury
Depression
Sundowning
Anxiety
Insomnia
“Past” Treatment of Agitation
• Agitation often treated non-specifically
with sedatives
–Should target underlying causes
• No medication is approved by the FDA for
agitation or aggression
–May reflect inconsistent concepts and
goals
Approach to Dyscontrol Syndromes
• Consider if due to:
–Depression
–Mania
–Psychosis
–Environmental factors
–Anxiety
• If so, treat accordingly
Evaluation of Cognitive and
Emotional Symptoms
•
•
•
•
Imaging (not usually very helpful)
Neuropsychological Assessment
Detailed past history
Differential etiologies
– Medications
– Concurrent illness
– Sleep disorders
Treatment of Post-Concussive
Affective/Emotional Problems
• Correct sleep disturbances
• Counseling Pharmacological
– SSRI’s
– Anticonvulsants (valproate, carbamazepine)
– Propranolol
– Psychostimulants
– Atypical antipsychotics ?
Approach to Depression
• Trials of
– SSRI
–second SSRI
–Low dose Desipramine or Bupropion
• Other
–MAOIs
–ECT
Approach to Mania
• Valproic Acid
• Lithium
• Combination approaches
• Newer anticonvulsants
–Lamotrigine
–Topirimate
Approach to Dyscontrol
• If not due to other conditions:
–Beta blockers
–Lithium
–SSRI’s
–Antipsychotics
–Calcium channel blockers
–Anticonvulsants
Nonpharmacological Approach
•
•
•
•
•
•
•
Modify environment
Optimize stimulation
Use consistent routines
Assess/adapt to aggravating factors
Behavior management principles
Education
Support of patient and caregivers
Flow Chart for Management
of Aggression
Employ nonpharmacologic
principles
Continue treatment as appropriate
Yes
No
Successful?
Depressive features
Antidepressants
Anticonvulsants
Lithium
Manic features
Anticonvulsants
Continue as appropriate
Consider eventual empirical withdrawal
Identify ,most prominent neurobehavioral sx cluster
match to relevant class
Anxious features
Antidepressants
Anticonvulsants
Anxiolytics
Effective?
Yes
Psychotic features
Aggression only
Empirical trials:
Antipsychotics
No
• blockers
•Anticonvulsants
•Lithium
•Antidepressants
•Atypicals
Adapted from Tariot et al; Ryan
Evidence Based Guidelines
• Workgroup for Neurobehavioral Consequences of TBI
– sponsored by IBIA, CDC
• Reviewed current literature
• Class I - randomized, double-blind, placebo controlled
• Class II - data collected prospectively, or retrospective
analyses based on clearly reliable data (observational,
cohort, prevalence, case control)
• Class III (case reports, retrospective, etc)
IBIA Evidence Based Review
of NBC of TBI
• There were no Class I, or II studies found
which addressed the treatment of
psychotic syndromes
• Some Class III studies addressed these
patient populations, many of these had
such methodological flaws that they were
not useable in establishing treatment
guidelines.
Class III – Psychotic Disorders
• Agents Used
– Typical Antipsychotics
• Chlorpromazine – Bamrah, 1991; n=1
– Atypical Antipsychotics
• Clozapine – Burke, 1999; n=1, Laddomada 1999; n=1
• Olanzapine – Butler, 2000; n=1, Umansky, 2000; n=1
• Risperidone – Schreiber, 1998; n=1
Side Effects and Toxicity
• Overall no clear indication from the literature
that those with TBI suffer increased frequency
or severity of side effects, nor novel side
effects/toxicity
• Usual side effects do occur:
– Akathisia on SSRI’s
– Mania on TCA’s and SSRI’s
– Sedation, weight gain, seizures on Clozapine
– Cognitive impairment on Lithium
• Not clear that this is different from those who
have not been injured
Conclusions
• The use of standard psychotropics for standard
indications (i.e. antipsychotics for the treatment
of psychosis) is an option for clinicians
– Use same meds, but dose differently
– Cannot match clinical profile to neurotransmitter
profile of various meds
– There is clearly a need for randomized clinical trials
to assess the efficacy of antidepressants,
anxiolytics, and antipsychotics in the treatment of
brain-injured individuals
Cognitive Symptoms
After Concussion
• Concentration and Attention
• Memory and learning
• Easily distracted
• Slowed thinking ,planning and problem solving
• Language function & communication deficit
Treatment of Post-concussive
Cognitive Problems
•
•
•
•
R/O contributing factors (Drug treatment)
Correct sleep disturbances
Counseling/Therapy
Pharmacological
– Psychostimulants
– Modafinil for excessive daytime fatigue
– Antidepressants
• SSRI’s
• TCA’s (desipramine)
• Buproprion
Approach to Cognitive Deficits
• Main target domains:
– Memory : particularly working memory
– Attention
– Executive Functions
• Management
– Baseline testing
– Trial of DA, A2A, or Cholinergic agent
– Methylphenidate – start 5 mg/day
– Aricept - start 5 mg/d
– Titrate up slowly as tolerated
– Discontinue after 2 months if no improvement