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PSYCHOPHARMACOLOGICAL APPROACHES TO NEUROBEHAVIORAL IMPAIRMENT FOLLOWNG ABI THIRD ANNUAL PACIFIC NORTHWEST BRAIN INJURY

PSYCHOPHARMACOLOGICAL APPROACHES TO NEUROBEHAVIORAL IMPAIRMENT FOLLOWNG ABI THIRD ANNUAL PACIFIC NORTHWEST BRAIN INJURY CONFERENCE. NATHAN D. ZASLER, MD CEO & MEDICAL DIRECTOR, CONCUSSION CARE CENTRE OF VIRGINIA AND TREE OF LIFE SERVICES CLINICAL PROFESSOR, DEPT. OF PM&R, VCU

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PSYCHOPHARMACOLOGICAL APPROACHES TO NEUROBEHAVIORAL IMPAIRMENT FOLLOWNG ABI THIRD ANNUAL PACIFIC NORTHWEST BRAIN INJURY

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  1. PSYCHOPHARMACOLOGICAL APPROACHES TO NEUROBEHAVIORAL IMPAIRMENT FOLLOWNG ABITHIRD ANNUAL PACIFIC NORTHWEST BRAIN INJURY CONFERENCE NATHAN D. ZASLER, MD CEO & MEDICAL DIRECTOR, CONCUSSION CARE CENTRE OF VIRGINIA AND TREE OF LIFE SERVICES CLINICAL PROFESSOR, DEPT. OF PM&R, VCU CLINICAL ASSOC. PROFESSOR, DEPT. OF PM&R, UVA

  2. PSYCHOPHARMACOLOGIC PRACTICES IN TBI • NO FDA APPROVED TREATMENTS FOR COGNITIVE OR BEHAVIORAL IMPAIRMENTS DUE TO TBI • PHARMACOTHERAPIES ARE GENERALLY MODELED AFTER THOSE FOR PATIENTS WITH PHENOMENOLOGICALLY SIMILAR BUT ETIOLOGICALLY DISTINCT DISORDERS

  3. GENERAL GUIDELINES • MINIMIZE POLYPHARMACY • KNOW YOUR DRUGS • CONSIDER ALTERNATE CHOICES • START LOW, GO SLOW • TITRATE BASED ON RESPONSE • BRING MEDICATIONS OR LIST • REVIEW REGULARLY • EDUCATE

  4. RULE FOR PRESCRIBERS • KNOW DRUG PROS AND CONS • KEEP UP WITH LITERATURE – IN GENERAL AND IN ABI • REMEMBER COST, COMPLIANCE AND QOL ISSUES • ASK, LISTEN, EDUCATE AND BE RESPONSIVE • MONITOR, MEDIATE AND MODULATE • ASSESS AND TREAT HOLISTICALLY • DO NOT TREAT IMPAIRMENTS IN ISOLATION OF FUNCTIONAL DISABILITIES

  5. QUESTIONS THAT SHOULD BE ASKED • WHAT DRUGS HAVE BEEN TRIED • WHAT WAS DURATION OF TREATMENT • WHAT DRUG DOSAGE WAS USED • WHY WAS DRUG PRESCRIBED IN FIRST PLACE • WHAT WERE DRUG TREATMENT GOALS

  6. DRUG SIDE-EFFECTS • ALL DRUGS HAVE SIDE-EFFECTS • SOME ARE BENIGN, SOME CAN BE FATAL • WITHDRAWAL VS. DISCONTINUATION SYNDROMES • IF YOU DON’T ASK YOU WON’T KNOW (E.G. SEXUAL PROBLEMS)

  7. DRUG SIDE-EFFECTS • DRUG INSERTS – DO’S & DON’TS • DOCS DON’T KNOW EVERYTHING • NEUROPSYCHIATRIC PATIENTS SHOW INCREASED FREQUENCY AND SEVERITY OF SIDE-EFFECTS • CAN MANIFEST AS WORSENING OF NEUROLOGICAL SYMTPOMS

  8. BEHAVIORAL ASSESSMENT MAY BE COMPROMISED BY: • IMPAIRED ATTENTION AND CONCENTRATION • IMPAIRED PLANNING AND PROBLEM SOLVING • IMPAIRED MEMORY AND LEARNING • IMPAIRED LANGUAGE FUNCTION

  9. BEHAVIORAL ASSESSMENT AND COMMUNICATION DEFICITS • PROPOSITIONAL AND PROSODIC FUNCTION CAN BE IMPAIRED • DIFFICULT TO MATCH AFFECT AND CONTENT • DENIAL SYNDROMES • LACK OF EXPERIENCE WITH PSYCHIATRIC LANGUAGE

  10. FILTER EFFECTS OF CNS INJURY • WHAT DOES DEPRESSION LOOK LIKE IN SOMEONE WHO IS NON-VERBAL? • WHAT DOES MANIA LOOK LIKE IN SOMEONE WHO IS QUADRIPARETIC OR EVEN WORSE LOCKED-IN? • HOW DO HALLUCINATIONS AND DELUSIONS PRESENT IN SOMEONE WHO CANNOT ADEQUATELY DESCRIBE THEM DUE TO DYSPHASIA?

  11. VULNERABILITY TO SIDE-EFFECTS • NEUROPSYCHIATRIC PATIENTS SEEM TO SHOW AN INCREASED FREQUENCY AND SEVERITY OF SIDE-EFFECTS TO MOST PSYCHOTROPICS • SIDE=EFFECTS CAN MANIFEST AS WORSENING OF NEUROLOGICAL SYMPTOMS: DYSARTHRIA, TREMOR, BRADYKINESIA, DECREASED COGNITION AND/OR BEHAVIOR

  12. NEUROBEHAVIORAL TREATMENT APPROACHES • IDENTIFY THE MOST SALIENT BEHAVIORAL SYMPTOM CLUSTER • DECIDE IF THE PATTERN IS ANALOGOUS TO A MORE TYPICALLY DRUG RESPONSIVE SYNDROME • USE AS A RATIONAL GUIDE TO THERAPY

  13. EXAMPLES OF METAPHORS: • “Depressive” Irritable, pessimistic, sad, weepy, socially withdrawn, vegetative features • “Psychotic” Angry when approached, overly suspicious, fragmented speech/thinking • “Manic” Euphoric, irritable, accelerated, hypersexual, reduced sleep

  14. STUFF DOCS FORGET • ALCOHOL • CAFFEINE • NICOTINE • OTC MEDICATIONS • NATUROPATHIC AGENTS • HOMEOPATHIC AGENTS • ILLICIT DRUGS

  15. DRUG TREATMENT IN ABI: CLASS EVIDENCE • PSYCHOSTIMULANTS • DOPAMINE AGONISTS • CHOLINOMIMETICS • SEROTONERGIC AGONISTS

  16. PSYCHOSTIMULANTS • 10 CONTROLLED STUDIES WITH METHYLPHENIDATE - 6 WITH COGNITION • MAJORITY OF STUDIES DEALING WITH COGNITION SHOWED POSITIVE EFFECT FROM MP • IMPROVEMENTS IN SUSTAINED ATTENTION, PROCESSING SPEED AND DISTRACTIBILITY

  17. PSYCHOSTIMULANTS • NO CONVINCING EVIDENCE THAT MP HAS A PRIMARY BENEFICIAL EFFECT ON MEMORY • EFFECT ON MOOD AND BEHAVIOR GENERALLY IN POSITIVE DIRECTION • MP DOES NOT APPEAR TO AFFECT MOTOR SPEED • MP MAY ENHANCE RATE OF NEURAL RECOVERY BUT NOT ULTIMATE PLATEAU

  18. PSYCHOSTIMULANTS • ONLY 2 CONTROLLED STUDIES IN BI WITH DEXTROAMPHETAMINE • IMPROVES COGNITIVE PROCESSING SPEED • NO GOOD DATA ON MEMORY OR MOOD/BEHAVIOR EFFECTS

  19. DOPAMINE AGONISTS • AMANTADINE IS BEST STUDIED OF ALL COMMONLY USED AGENTS • INCONSISTENT EFFECTS BUT GENERALLY FACILITATE ATTENTION, CONCENTRATION AND MODULATE BEHAVIOR • MAY MODULATE FRONTAL LOBE IMPAIRMENTS • DRUG CLASS OF CHOICE IN AM • CLASS AS A WHOLE USED MOST FREQUENTLY TO FACILITATE NEURORECOVERY IN MCS AND MODULATE BRADYKINETIC SYMPTOMS

  20. CHOLINOMIMETICS • ALTHOUGH THERE ARE SEVERAL AGENTS IN CLASS NONE HAVE BEEN WELL STUDIED IN ND-ABI • DONEPEZIL IS BEST STUDIED AGENT IN TBI • NEWER AGENTS APPEAR MORE PROMISING THAN OLDER ONES (E.G. TACRINE) DUE TO SPECIFICITY AND SIDE-EFFECT PROFILE • MAY HAVE BOTH COGNITIVE AND BEHAVIORAL BENEFITS

  21. SEROTONERGIC AGONISTS • LIMITED STUDIES EXIST IN TBI • GENERALLY WELL TOLERATED • LIKELY EFFECTIVE FOR A VARIETY OF BEHAVIORAL SPECTRUM DISORDERS • CARE NEEDS TO BE TAKEN WHEN COMBINING AGENTS AND/OR WITHDRAWING DRUG

  22. COMMON PSYCHOSTIMULANT DRUGS AND DOSING • METHYLPHENIDATE: 2.5 - 5 BID, MAX 20 TID • AMPHETAMINE & DEXTROAMPHETAMINE: 5 QDAY, MAX 60/DAY (SPLIT) • DEXTROAMPHETAMINE: 5 QDAY, MAX 60/DAY (SPLIT) • PEMOLINE: 18.75 - 37.5 QDAY, MAX 112.5/DAY

  23. COMMON DOPAMINERGIC DRUGS AND DOSING • L-DOPA/CARBIDOPA: 10 - 25 TID • AMANTADINE HCL: 50 BID, MAX 200 BID • BROMOCRIPTINE: 2.5 BID, MAX 40 TID • PERGOLIDE: .05/DAY, 5 MG/DAY (TID) • ROPINIROLE: .25 TID, MAX 24/DAY • PRAMIPEXOLE: .125 TID, MAX 1.5 TID • SELEGELINE:5 QDAY, MAX 5 BID

  24. COMMON CHOLINOMIMETIC DRUGS AND DOSES • DONEZEPIL: 5/DAY, MAX 10/DAY • RIVASTAGMINE: 1.5 BID, MAX 6 BID • GALANTAMINE: 4 BID, MAX 12 BID • CDP-CHOLINE: 250 BID, MAX 1000 BID

  25. COMMON PROSEROTONERGIC DRUGS AND DOSES • AMITRYPTILINE: 10 QHS, MAX 300/DAY • NORTRIPTYLINE: 10 QHS, 150/DAY IN DIVIDEDED DOSES • PROTRIPTYLINE: 5 QDAY, MAX20 TID • DOXEPIN: 10 QHS, MAX 300/DAY • IMIPRAMINE: 10 QHS, MAX 300/DAY

  26. COMMON PROSEROTONERGIC (SSRI) DRUGS AND DOSES • FLUOXETINE: 10 QDAY, MAX 90/DAY • PAROXETINE: 10 QDAY, MAX 50/DAY • SERTRALINE: 50/DAY, MAX 200/DAY • FLUVOXAMINE:50 QHS, MAX 300/DAY • CITALOPRAM: 10/DAY, MAX 60/DAY • ESCITOLOPRAM: 10/DAY, MAX 20

  27. OTHER ANTIDEPRESSANTS • VENLAFAXINE: 37.5 QDAY, MAX 375/DAY • BUPROPRION: 75/DAY, MAX 450/DAY • DULOXETINE: 20/DAY, MAX 60/DAY • TRAZODONE: 50/DAY, MAX 600/DAY • NEFAZODONE: 50/DAY, MAX 300 BID • MIRTAZAPINE: 15/DAY, MAX 45/DAY

  28. ANTIPSYCHOTIC DRUGS AND DOSING • HALOPERIDOL: .5 BID, MAX 100/DAY • THIORIDAZINE: 50 TID, MAX 800/DAY • RISPERDONE: 1 BID, MAX 4 BID • QUETIAPINE: 25 BID, MAX 800/DAY • OLANZAPINE: 2.5/DAY, MAX 20/DAY • ZIPRASIDONE: 20 BID, MAX 80 BID

  29. PSYCHOTROPIC ANTICONVULSANTS AND DOSES • VALPROIC ACID: 15 MG/KG, MAX 60/MG/KG • TOPIRAMATE: 25 QHS, MAX 400 BID • LAMOTRIGINE:50 QDAY, MAX 250 BID • OXCARBAZEPINE: 300 QDAY, MAX 1200 BID • GABAPENTIN: 10 MG/KG, 1200 TID • ZONISAMIDE: 50/DAY, MAX 300 BID • LEVETIRACETAM: 500 BID, 1500 BID

  30. ANTIANXIETY DRUGS AND DOSES • BUSPIRONE: 7.5 BID, MAX 30 BID • ALPRAZOLAM: .25 TID, MAX 4/DAY • CLONAZEPAM: .5 QDAY, MAX 20/DAY • SSRIs - SEE PRIOR SECTION

  31. MISCELLANEOUS DRUGS AND DOSES • PROVIGIL: 100 QDAY, 200 BID • ZOLPIDEM: 5 QHS, MAX 10 QHS • ZALEPLON: 5 QHS, MAX 20 QHS • LITHIUM: 300 QDAY, MAX DOSE = DOSE NEEDED TO ACHIEVE LEVEL OF .6 – 1.2 • NALTREXONE: 50 QDAY, MAX 100 QDAY

  32. DIFFERENTIAL DIAGNOSIS OF BEHAVIORAL DYSFUNCTION • ABI • PT-AFFECTIVE AND/OR ADJUSTMENT ISSUES • PRE-EXISTING AFFECTIVE ISSUES • AGGRAVATION OF PRE-EXISTING CHARACTEROLOGICAL TRAIT AND/OR AFFECTIVE DISORDER • PT-MEDICAL ISSUES • UNRELATED MEDICAL ISSUES • DRUG RELATED SIDE-EFFECTS • DISSIMULATED

  33. STRESS AND IMPACT ON COGNITION & BEHAVIOR • PHYSIOLOGIC EFFECTS • NEUROHORMONAL AND NEUROTRANSMITER CHANGES • PSYCHOLOGICAL EFFECTS • NEGATIVE INFLUENCES ON ATTENTION, CONCENTRATION AND FRUSTRATION TOLERANCE • PATHOANATOMICAL EFFECTS • SUBCORTICAL/HIPPOCAMPAL ATROPHY

  34. SPECIFIC BEHAVIORAL IMPAIRMENTS • FATIGUE/HYPOAROUSAL • HYPERSOMNOLENCE • LIBIDINAL ALTERATIONS • APATHY/ABULIA/LACK OF INITIATION • DYSPHORIA AND DEPRESSION • ANXIETY SPECTRUM DISORDERS INCLUDING PHOBIAS AND PTSD

  35. SPECIFIC BEHAVIORAL IMPAIRMENTS • IRRITABILITY/AGGRESSION • EMOTIONAL LABILITY • OCD • PARANOIA/PSYCHOSIS • MANIA • BPD

  36. TBI and Psychiatric DisordersFrom van Reekum et al. Can traumatic brain injury cause psychiatric disorders? J Neuropsychiatry 12:316-327, 2000

  37. FATIGUE • MOST COMMON CAUSES ARE AFFECTIVE ISSUES AND POOR SLEEP • NEUROGENIC FATIGUE IS A DIAGNOSIS OF EXCLUSION • NEUROMEDICAL ISSUES INCLUDING CHRONIC PAIN CAN PRESENT WITH DEPRESSION • IF DRUGS USED, HAVE ADEQUATE MEASURE PRE- AND POST-TREATMENT AND CORROBORATE PATIENT REPORT AS POSSIBLE • PSYCHOSTIMULANTS ARE NOT THE ONLY DRUGS THAT WORK FOR FATIGUE, CONSIDER NON-CONTROLLED AGENTS FIRST

  38. HYPOAROUSAL AND HYPERSOMNOLENCE • MAY BE RELATED TO SLEEP PROBLEM, UNDERSTIMULATION/BOREDOM, MEDICAL CONDITION, MEDICATION SIDE-EFFECT OR LOW LEVEL NEUROLOGIC STATE • TREAT WHAT CAN BE TREATED FIRST THEN CONSIDER MEDS • DIMS VS. DOES: TX. IMPLICATIONS • SLEEP HYGIENE AND PSGs • DEPENDING ON PRESENTATION, CONSIDER DA AGONISTS AND/OR PSYCHOSTIMULANTS

  39. LIBIDINAL ALTERATIONS • TRUE HYPERSEXUALITY IS UNCOMMON (E.G. KBS) • TREATMENTS INCLUDE BM AND/OR MEDS (HORMONAL OR SEROTONERGIC). IF KBS MAY RESPOND TO AED. • DECREASED LIBIDO • CHECK HORMONES FIRST • GET GOOD HISTORY & R/O DRUG SIDE-EFFECTS • CONSIDER BEHAVIORAL THERAPIES • CONSIDER DRUG TREATMENT - NORADRENERGIC AGENTS, TESTOSTERONE SUPPLEMENTATION

  40. DYSPHORIA AND DEPRESSION • APATHY AND ABULIA MAY BE RELATED TO DEPRESSION AND/OR ORGANICALLY CAUSED • DEPRESSION IS SOMETIMES “OVER-DX’D” • FRONTAL BEHAVIORAL SYNDROMES AND DRUG TREATMENT • DEPRESSIVE MOOD DISORDERS AND DRUG TREATMENT • THERE IS NO “MAGIC” DRUG • CHOOSE DRUG BASED ON PATIENT PROFILE • CONSIDER AUGMENTATION IF SUBOPTIMAL RESPONSE • IF ACUTELY DEPRESSED CONSIDER METHYLPHENIDATE

  41. ANXIETY SPECTRUM DISORDERS • ASDs ARE MORE COMMON IN PERSONS WITH TBI THAN GENERALLY ACKNOWLEDGED • SUB-SYNDROMAL PTSD IS NOT UNCOMMON AND SYNDROMAL PTSD IS SOMETIMES MISSED • MTBI AT TIMES DX’D INSTEAD OF PTSD • THINK ABOUT ASD IN MTBIs WHO ARE NOT GETTING BETTER • CHRONIC PAIN PROMULGATES ASDs • GOOD TREATMENT COMBINES BEHAVIORAL MEDICINE AND PHARMACOTHERAPEUTICS

  42. IRRITABILITY AND AGGRESSION • IRRITABILITY VERY COMMON FOLLOWING TBI • TRUE PHYSICAL AGGRESSION NOT PARTICULARLY COMMON IN POST-ACUTE PHASE • GENERALLY, THIS BEHAVIORAL CLASS OF IMPAIRMENTS RESPONDS WELL TO SSRIs AND/OR PSYCHOTROPIC ANTICONVULSANTS

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