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Psychiatric Problems Following TBI

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

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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

  2. 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

  3. 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)

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

  5. 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

  6. Mayberg et al, J Neuropsychiatry Clin Neurosci

  7. 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

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

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

  10. Neuropsychiatric Sequelae • Delirium • Depression • Mania • Anxiety • Psychosis • Cognitive Impairment • Aggression, Agitation, Impulsivity • Insomnia

  11. 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

  12. Neuropsychiatric Evaluation and Treatment: Etiologies PsychiatricNeurologic/MedicalSocial 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

  13. Neuropsychiatric Evaluation and Treatment: Workup PsychiatricNeurologic/MedicalSocial 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. Patient Health Questionnaire - 9 Spitzer et al. JAMA 1999

  22. Rates Of Major Depression After TBI 53% N = 559

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

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

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

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

  27. Comorbidity of Anxiety and MDD Any comorbid anxiety disorder in MDD+ vs. MDD- (60% vs. 7%; RR, 8.77; CI, 5.56-13.83)

  28. 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

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

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

  31. 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

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

  33. 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 LifeImprovement Following Traumatic Brain Injury:A Trial of Cognitive-Behavioral Therapy for Depression after TBI

  34. 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

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

  36. 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

  37. 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

  38. Rates of Anxiety Disorders (civilians) NA = Not Assessed.

  39. 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

  40. Adjustment Disorders • Clinically significant symptoms of depressed mood, anxiety, or both • Occurringwithin 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.

  41. 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*

  42. 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

  43. 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*

  44. 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 PTSD Risk Factors

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

  46. 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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