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Psychiatric Problems Following TBI

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

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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

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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
Psychiatric Neurologic/Medical Social Premorbid Neurologic illness Social, family, vocation Psych disorders & sxs. Lesion location, size, Rehabilitation situation Personality traits pathophysiology and stressors Coping styles Other medical illness Functional impairment Substance Abuse Other indirect sequelae Medicolegal Medication side effects (e.g., pain, sleep disturb) & interactions Medication 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
Psychiatric Neurologic/Medical Social Psychiatric history & Medical history and Interview family, friends, examination physical examination caregivers Neuropsychological Appropriate lab tests Assess level of care & testing e.g., CBC, med blood supervision available Psychodynamic signif. of levels, CT/MRI, EEG Assess 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)
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

23 Transdiagnostic Symptoms
TBI Depressed mood Anhedonia Weight loss/gain Insomnia/hypersomnia X Psychomotor changes X Fatigue X Worthlessness/guilt Poor concentration X 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 Nearly every day 1. Little interest or pleasure in doing things 1 2 3 2. Feeling down, depressed, or hopeless 3. Trouble falling or staying asleep, or sleeping too much 4. Feeling tired or having little energy 5. Poor appetite or overeating 6. Feeling bad about yourself — or that you are a failure or have let yourself or your family down 7. Trouble concentrating on things, such as reading the newspaper or watching television 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 9. Thoughts that you would be better off dead or of hurting yourself in some way Spitzer et al. JAMA 1999

25 Rates Of Major Depression After TBI
53% N = 559

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
81% 51% 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

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

36 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

37 Reason Accommodations 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 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 Rates of Anxiety Disorders (civilians)
GAD PTSD OCD Panic Phobias Sample 24% NA 4% 2% Agoraphobia 50 patients diagnosed with TBI seen at a rehabilitation clinic -mean 32.5 months post injury Fann et al., 1995 8% 17% 14% 11% 7% 100 patients with TBI - mean 7.6 years post injury Hibbard et al., 1998 3% 2% 9% 1% 100 patients hospitalized for TBI - 1 year post injury Deb et al., 1999 6% Specific Phobia Social Phobia 1% Agorophobia 100 patients hospitalized for TBI - assessed years post injury Whelan-Goodinson et al., 2009 13.4% 13% 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.

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
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 Avoid places, activities C. Dissociative amnesia* Diminished interest Detachment from others Restricted affect* Foreshortened future CLUSTER D: Arousal At least 2 of: A. Sleep disturbance* B. Anger* Concentration difficulties* Hypervigilence 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

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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

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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

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

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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