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Psychiatric Problems Following TBI Jesse R. Fann, MD, MPH Departments of Psychiatry and Behavioral Sciences, Rehabilitation Medicine, & Epidemiology University.

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Presentation on theme: "Psychiatric Problems Following TBI Jesse R. Fann, MD, MPH Departments of Psychiatry and Behavioral Sciences, Rehabilitation Medicine, & Epidemiology University."— Presentation transcript:

1 Psychiatric Problems Following TBI Jesse R. Fann, MD, MPH Departments of Psychiatry and Behavioral Sciences, Rehabilitation Medicine, & Epidemiology University of Washington Seattle, Washington



4 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

5 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)

6 Non-penetrating TBI Diffuse Axonal Injury Contusion Subdural Hemorrhage Taber et al 2006

7 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

8 Mayberg et al, J Neuropsychiatry Clin Neurosci

9 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

10 Psychiatric Illness in Adult HMO Enrollees (N=939 with TBI, 2817 controls) Fann et al. Arch Gen Psychiatry 2004; 61:53-61

11 Psychiatric Disorder & MTBI Bryant et al., Am J Psychiatry, in press


13 Neuropsychiatric Sequelae Delirium Depression Mania Anxiety Psychosis Cognitive Impairment Aggression, Agitation, Impulsivity Insomnia

14 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

15 Neuropsychiatric Evaluation and Treatment: Etiologies PsychiatricNeurologic/MedicalSocial PremorbidNeurologic illnessSocial, family, vocation Psych disorders & sxs. Lesion location, size,Rehabilitation situation Personality traits pathophysiology and stressors Coping stylesOther medical illnessFunctional impairment Substance AbuseOther indirect sequelaeMedicolegal Medication side effects (e.g., pain, sleep disturb) & interactionsMedication side effects Psychodynamic signif. & interactions of neurologic illness Family psych. history Roy-Byrne P, Fann JR. APA Textbook of Neuropsychiatry, 1997

16 Neuropsychiatric Evaluation and Treatment: Workup PsychiatricNeurologic/MedicalSocial Psychiatric history &Medical history and Interview family, friends, examination physical examination caregivers NeuropsychologicalAppropriate lab testsAssess level of care & testing e.g., CBC, med blood supervision available Psychodynamic signif. of levels, CT/MRI, EEGAssess rehab needs neuropsychiatric sxs.,Medication allergies & progress disability and treatments

17 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

18 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

19 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 self- management, 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

20 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

21 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:

22 DSM-IV Major Depressive Disorder (MDD) 1.Depressed mood* 2.Loss of interest/pleasure* 3.Sleep disturbance 4.Poor energy 5.Motor change agitation or slowness 6.Weight/appetite change increase/decrease 7.Impaired concentration or indecision 8.Excessive worthlessness or guilt 9.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, 4 th ed, 2000

23 Transdiagnostic Symptoms TBI 1.Depressed mood 2.Anhedonia 3.Weight loss/gain 4.Insomnia/hypersomnia X 5.Psychomotor changes X 6.Fatigue X 7.Worthlessness/guilt 8.Poor concentration X 9.Thoughts of death/suicide

24 Patient Health Questionnaire - 9 Over the last 2 weeks, how often have you been bothered by any of the following problems? Not at all Several days More than half the days Nearly every day 1. Little interest or pleasure in doing things Feeling down, depressed, or hopeless Trouble falling or staying asleep, or sleeping too much Feeling tired or having little energy Poor appetite or overeating Feeling bad about yourself — or that you are a failure or have let yourself or your family down Trouble concentrating on things, such as reading the newspaper or watching television 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 Thoughts that you would be better off dead or of hurting yourself in some way 0123 Spitzer et al. JAMA 1999

25 Rates Of Major Depression After TBI N = %

26 Point Prevalence of MDD Range 21-31%, no trend

27 Cumulative Rate of MDD as a Function of Depression History 73%* 69%* 41% *P <.001; independent predictors after adjusting for all other variables

28 Rate of MDD by History of Lifetime Alcohol Dependence 70%* 45% *P <.001; independent predictor after adjusting for all other variables

29 Cumulative Rate of MDD by PTSD History 51% 81% Univariate predictor, not significant after adjusting for other variables

30 Comorbidity of Anxiety and MDD Any comorbid anxiety disorder in MDD+ vs. MDD- (60% vs. 7%; RR, 8.77; CI, )

31 Depression / Apathy Selective serotonin re-uptake inhibitors (SSRIs) -sertraline - paroxetine- fluoxetine -citalopram - escitalopram -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, modafinil Fann et al, J Neurotrauma 2009

32 Number of Postconcussive Symptoms All symptoms *Depressive symptoms excluded * p=.05

33 PCS – Depression Study (Baseline and Week 8) ** * * * *p<.05 **p<.01

34 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

35 Modifiable Risk Factors Neurobiological Factors Cognitive Distortions No Pleasant Activities Sedentary Lifestyle Psychosocial Adversity Depression

36 Life Improvement Following Traumatic Brain Injury: A Trial of Cognitive-Behavioral Therapy for Depression after TBI 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 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

37 ReasonAccommodations Slowed information processing & responding Present information at slower rate Allow client more time to respond Provide written summary of session beforehand Impaired attention & concentration 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 & recall Provide written summary of session (patient workbook) Assign simple written homework Provide written educational materials or workbook Plan additional practice of CBT skills within session (over-learn skills) Impaired verbal abilities Minimize emphasis on verbally mediated aspects of CBT Emphasize behavioral activation and pleasant events scheduling Impaired initiation & generalization Include family or friend in treatment planning and homework assignments Provide 2 sessions devoted to generalization and relapse prevention at end Impaired motivation 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

38 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:

39 Mania Acute –Benzodiazepines –Antipsychotics »olanzapine, risperidone, quetiapine, clozapine –Anticonvulsants »valproate –Electroconvulsive Therapy Chronic –valproate –carbamazepine –lamotrigine –lithium carbonate (neurotoxicity) –gabapentin, topiramate (adjunctive treatments)

40 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

41 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

42 GADPTSDOCDPanicPhobias Sample 24%NA 4% 2% Agoraphobia50 patients diagnosed with TBI seen at a rehabilitation clinic -mean 32.5 months post injury Fann et al., %17%14%11% 7%100 patients with TBI - mean 7.6 years post injury Hibbard et al., % 2%9% 1%100 patients hospitalized for TBI - 1 year post injury Deb et al., %14%1%6% 7% Specific Phobia 6% Social Phobia 1% Agorophobia 100 patients hospitalized for TBI - assessed years post injury Whelan- Goodinson et al., %13%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 NA = Not Assessed. Rates of Anxiety Disorders (civilians)

43 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:

44 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.

45 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*

46 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 least 2 of: A. Sleep disturbance* B. Anger* C.Concentration difficulties* D.Hypervigilence E.Elevated startle response

47 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*

48 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

49 Psychiatric Disorder & Prior Sleep Problems Bryant et al., Sleep, in press

50 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


52 Interface of PTSD & Persistent PCS Stein & McAllister, AJP 2009

53 Brain regions implicated in PTSD and vulnerable to TBI

54 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

55 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

56 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.

57 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

58 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

59 Psychosis Hallucinations, delusions, thought disorder Immediate or latent onset Symptoms may resemble schizophrenia: prevalence 0.7%* in TBI Schizophrenics have increased risk of TBI pre- dating psychosis Patients developing schizophrenic-like psychosis over years is % Look for epileptiform activity and temporal lobe lesions Treatment: Antipsychotic medications (referral) * van Reekum et al. J Neuropsychiatry Clin Neurosci 2000;12:

60 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)

61 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



64 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

65 Cognitive Impairment May impede recovery haloperidol phenothiazines prazosin clonidine phenoxybenzamine GABAergic agents benzodiazepines Phenytoin carbamazepine phenobarbital idazoxan

66 Aggression, Irritability, Impulsivity Up to 70% within 1 year of TBI May last over years Interview family and caregivers, if possible Characteristic features –Reactive- Explosive –Non-reflective- Periodic –Non-purposeful- Ego-dystonic Treat other underlying etiologies (e.g., bipolar) Treatment: Medications and behavioral interventions


68 Pilot study of sertraline (N=15) Brief Anger / Aggression Questionnaire (BAAQ) Fann et al. Psychosomatics 2001; 42:48-54

69 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

70 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

71 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

72 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

73 Proposed Model TBI Psychiatric Vulnerability Postconcussive Symptoms Cognition Neurosychiatric Symptoms Health Care Utilization Functioning/ QOL + +/- TBI Severity +,-

74 “The significant problems we face cannot be solved at the same level of thinking we were at when we created them” Albert Einstein

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