MEDICATIONS TO ENHANCE COGNITIVE FUNCTION AFTER TRAUMATIC BRAIN INJURY

COGNITIVE DYSFUNCTION
COGNITIVE & BEHAVIOURAL DYSFUNCTION AFTER TBI - MORE DEVASTATING THAN RESIDUAL PHYSICAL DEFICITS FORMAL RECOMMENDATIONS FOR PHARMACOLOGICAL INTERVENTIONS ARE STILL PENDING

COGNITIVE DYSFUNCTION AFTER TBI

MEMORY ATTENTION LANGUAGE PERCEPTION EXECUTIVE FUNCTIONS

AGENTS TO ENHANCE COGNITION POST TBI

LITTLE RESEARCH HAS BEEN DONE ON MEDICATIONS FOR TBI SUBJECTS METHODOLOGICAL PROBLEMS WITH STUDIES - OUTCOME MEASURES? CANNOT CONTROL THE INFLUENCE OF LEARNING POST TBI IN RESEARCH STUDIES CANNOT CONTROL FOR NATURAL HX. OF RECOVERY AFTER TBI IN RESEARCH SUBJECTS (PLASTICITY)

NEUROTRANSMITTER SYSTEMS AND COGNITION

THREE NEUROTRANSMITTER SYSTEMS HAVE A ROLE IN COGNITIVE PERFORMANCE AFTER TBI: ACETYLCHOLINE DOPAMINE NOREPINEPHRINE

DRUG INTERVENTIONS FOR MEMORY ENHANCEMENT

CHOLINERGIC SYSTEM-MEDIATES MEMORY, LEARNING, & ATTENTION POST TBI CHOLINERGIC HYPOTHESIS OF MEMORY- EVOLVED FROM OBSERVATIONS IN ALZHEIMERS PTS. DISRUPTION OF CHOLINERGIC NEURONS

CHOLINERGIC HYPOTHESIS OF MEMORY

AMYGDALA HIPPOCAMPUS BASAL NUCLEUS OF MEYNERT THESE AREAS ARE RICH IN CHOLINERGIC NEURONS THESE REGIONS ARE FREQUENTLY DAMAGED IN TBI

MEDICATIONS TO IMPROVE ATTENTION & AROUSAL

BRAIN STRUCTURES INVOLVED IN REGULATION & MEDIATION OF ATTENTION/AROUSAL INCLUDE: MESENCEPHALON BASAL GANGLIA LIMBIC SYSTEM CEREBRAL CORTEX

NOREPINEPHRINE: ROLE IN ATTENTION/AROUSAL

NOREPINEPHRINE: NEURONS RICH IN NE FOUND IN .. LOCUS CAERULEUS LATERAL TEGMENTAL SYSTEM A DIFFUSE SET OF PROJECTIONS FROM THESE AREAS EXTEND TOWARDS THE FOREBRAIN

DOPAMINE
NEURONS CONTAINING DOPAMINE IN THE SUBSTANTIA NIGRA/ NIGROSTRIAL PATHWAYS HYPOTHALAMUS MESOCORTICAL/MESOLIMBIC PATHWAYS VENTRAL TEGMENTUM MEDIATE AROUSAL, MENTATION, AS WELL AS MOTOR CONTROL

CHOLINOMIMETIC AGENTS
CONTROVERSY : SHOULD THESE AGENTS ONLY BE USED IN CHRONIC TBI TO IMPROVE COGNITION ? BECAUSE IN ACUTE TBI,CHOLINERGIC ACTIVITY IS IMPLICATED IN THE CASCADE OF NEUROCHEMICAL CHANGES LEADING TO NEURONAL DEATH

CHOLINERGIC PRECURSORS
LECITHIN CHOLINE CYTIDINE DIPHOSPHOCHOLINE TRIALS HAVE BEEN DONE TO STUDY POSSIBLE IMPROVEMENT IN MEMORY AFTER TBI & DEMENTIA

LECITHIN AND CHOLINE

NO SIGNIFICANT INCREASES IN CNS LEVELS OF ACETYLCHOLINE WHEN USED IN ANIMALS IN A FEW STUDIES,THESE WERE INCREASED ACH IN STRIATUM NOT AS IMPORTANT TO LEARNING/MEMORY AS HIPPOCAMPUS

CHOLINERGIC PRECURSORS AS COGNITIVE ENHANCING AGENTS CONFLICTING RESULTS IN TBI MODEST COGNITIVE BENEFIT POSITIVE RESULTS PRIMARILY IN YOUNG HEALTHY SUBJECTS EFFECTS OF CHOLINERGIC PRECURSORS IN ALZHEIMERS & VASCULAR DEMENTIA - NOT EVIDENT IN STUDIES

DOSING
16-20 GRAMS PER DAY OF CHOLINE 25 GRAMS OF LECITHIN PER DAY THESE ARE THE MAXIMAL TOLERATED DOSAGES WITHOUT SIGNIFICANT SIDE EFFECTS

CYTIDINE DIPHOSPHOCHOLINE
A METABOLIC INTERMEDIATE DISSOCIATES TO CHOLINE AND CYTIDINE AFTER INGESTION IN MILD & MODERATE TBI,CITICHOLINE PRODUCED IMPROVEMENTS IN RECOGNITION & MEMORY COMPARED TO PLACEBO TREATED SUBJECTS

CITICHOLINE
CALATAYUD, 1991 SINGLE BLIND RANDOMIZED STUDY OF 216 SUBJECTS WITH SEVERE OR MODERATE TBI IN THE ACUTE POST INJURY PERIOD IMPROVEMENTS IN MOTOR, COGNITIVE, AND PSYCHIATRIC FUNCTIONING, DECREASED LENGTH OF STAY IN HOSPITAL

CITICHOLINE IN TBI
SHORTENS COMA DURATION SHORTENS LENGTH OF HOSPITAL STAY IMPROVES GLASCOW OUTCOME SCALE AT DISCHARGE DOSE 250-6000 MG PER DAY
LOZANO, J.NEUROL.SCI., 1991

ADVERSE EFFECTS OF CHOLINERGIC PRECURSORS

SALIVATION SWEATING ANOREXIA NAUSEA VOMITING DIARRHEA BLOATING

CITICHOLINE
AVAILABLE AS AN OVER THE COUNTER SUPPLEMENT 250 MG CAPSULES NO FORMAL RECOMMENDATIONS ON DOSAGE ARE AVAILABLE

CHOLINESTERASE INHIBITORS
CARBAMATE TYPE ORGANOPHOSPHATE TYPE CARBAMATE CHOLINESTERASE INHIBITORS - REVERSIBLE ORGANOPHOSPHATE CHOLINESTERASE INHIBITORS IRREVERSIBLEUSED FOR BIOLOGICAL WARFARE

PHYSOSTIGMINE
PO, IV, OR IM ADMINSTRATION HALF LIFE OF 30 MINUTES CROSSES BLOOD BRAIN BARRIER SHORT DURATION OF ACTION MAKES IT IMPRACTICAL FOR USE IN TBI PATIENTS A CARBAMATE ANTICHOLINESTERASE

PHYSOSTIGMINE
USE OF PHYSOSTIGMINE IN ALZHEIMERS PATIENTS - MIXED RESULTS, ? IMPROVEMENT LECITHIN 20 MG & PHYSOSTIGMINE 1-8 MG COMBINATION-IMPROVES VERBAL MEMORY AFTER TBI -GOLDBERG ET AL, J.
CLIN.NEUROPSYCH., 1982

SIDE EFFECTS - SIMILAR TO OTHER CHOLINERGIC AGENTS

DONEPEZIL (ARICEPT)
ACETYLCHOLINESTERASE INHIBITOR CARBAMATE TYPE CASE STUDIES INVOLVING 9 TBI SUBJECTS IMPROVEMENTS IN MEMORY ON MMSE - WHITLOCK,1999

DONEPEZIL
ZHANG ET AL, 2004 24 WEEK RANDOMIZED PLACEBO CONTROLLED DOUBLE BLIND CROSSOVER TRIAL OF DONEPEZIL 10 MG / DAY IN SUBJECTS 2 24 MONTHS POST INJURY IN 18 SUBJECTS SUBJECTS WERE RLA 6 OR HIGHER TREATMENT GROUP DEMONSTRATED IMPROVED COGNITIVE FUNCTION ON TESTS OF ATTENTION & MEMORY

ARICEPT
WHELAN, 2000 OPEN LABEL TRIAL OF DONEPEZIL IN 53 TBI OUTPATIENTS TREATED WITH 5 10 MG DAILY FOR 12 MONTHS IMPROVEMENTS IN IQ TESTING WERE OBSERVED ON WAIS R

ARICEPT
PROVEN SAFE/ EFFECTIVE IN TREATMENT OF MILD MODERATE ALZHEIMERSIMPROVES MEMORY NO IMPROVEMENT IN ADL DOSE IS 5 MG PO QD FOR FIVE WEEKS, THEN TITRATE UP TO 10 MG PER DAY, IF TOLERATED

GALANTAMINE (REMINYL)
A RECENT CASE REPORT INDICATES IT IS NOT HELPFUL IN TBI (JOHNSON ET AL,PSYCHOSOMATICS, 2007) CARBAMATE ANTICHOLINESTERASE THIS DRUG IMPROVES COGNITIVE FUNCTION & ADL IN PATIENTS WITH MILD - MODERATE ALZHEIMERS DISEASE

GALANTAMINE
IF YOU WANT TO TRY IT IN YOUR PATIENTS START AT 8 MG PER DAY TITRATE UP BY 8 MG INCREMENTS EVERY WEEK TO A MAXIMAL DOSE OF 32 MG PER DAY

RIVASTIGMINE (EXELON)
DOUBLE BLIND PLACEBO CONTROLLED RANDOMIZED TRIAL IN 157 TBI SUBJECTS AT LEAST ONE YEAR POST INJURY

In a subgroup of patients with moderate to severe memory impairment (n = 81), defined as 25% impairment or greater on neuropsychological testing at baseline, rivastigmine was significantly better than placebo in performance on memory testing & visual information processing Small but statistically significant gains were noted

RIVASTIGMINE (EXELON)
IF YOU WANT TO TRY IT FOR YOUR PATIENTS START AT 1.5 MG PO BID INCREASE BY 1.5 MG BID INCREMENTS EVERY 4 WEEKS TILL CLINICAL IMPROVEMENT IS NOTED

SIDE EFFECTS OF CHOLINESTERASE INHIBITORS

HEADACHE NAUSEA DIARRHEA VOMITING PAIN MUSCLE CRAMPING INSOMNIA FATIGUE CANNOT USE THESE AGENTS FOR PATIENTS WITH FIRST DEGREE AV BLOCK & SYMPTOMATIC BRADYCARDIA DONT USE WITH KETOCONAZOLE OR QUINIDINE, AS THESE AGENTS CAN INCREASE ARICEPT LEVELS TITRATE DOSE UP SLOWLY OR THESE SIDE EFFECTS WILL BE SEEN

NORADRENERGIC AGENTS IN TBI

CLONIDINE ALPHA 2 RECEPTOR AGONIST, STIMULATES ADRENERGIC RECEPTORS IN THE BRAINSTEM DECREASES SYMPATHETIC OUTFLOW FROM THE CNS USED FOR PREVENTION OF OPIATE WITHDRAWAL ANTIHYPERTENSIVE MANAGEMENT OF SPASTICITY

CLONIDINE
IN ANIMAL MODELS,IT IMPROVES WORKING MEMORY & REDUCES DISTRACTIBILITY NOT EFFECTIVE IN HUMANS WITH TBI IN STUDIES MIXED OUTCOMES FOR PATIENTS WITH KORSAKOFFS & ALZHEIMERS WITH CLONIDINE

CLONIDINE IN TBI
IN ACUTE TBI,HAS A NEGATIVE EFFECT ON MOTOR RECOVERY USE OF CLONIDINE IN CHRONIC HEMIPLEGIC HUMANS CAN TRANSIENTLY REINSTATE MOTOR DEFICITS SUCH AS HEMIPLEGIA

AMPHETAMINES
CATECOLAMINE AGONISTS, ACT PRIMARILY BY INCREASING DOPAMINE DEXTROAMPHETAMINE (DEXEDRIN) - MOST COMMONLY USED - 0.1- 0.2 MG PER KG TYPICAL STARTING DOSE IN AN ADULT : 5 MG PO BID INCREASE BY 5 10 MG / WEEK STANDARD ADULT DOSE:10 - 60 MG PO QD QUICK ONSET OF ACTION

DEXTROAMPHETAMINE FOR TX. OF APHASIA

DEXTROAMPHETAMINE 10 MG QD 1 HOUR BEFORE SPEECH THERAPY IMPROVED VERBAL OUTPUT WALKER-BATSON, CLINICAL APHASIOLOGY, 1991

DEXTROAMPHETAMINE
ADMINISTERED DEXTROAMPHETAMINE 0.1 AND 0.2 MG / KG BODY WEIGHT IMPROVED MEMORY, ATTENTION,PROCESSING SPEED, MOTOR SPEED, & MOOD AFTER TBI IN ONE CASE STUDY (EVANS & GUALTIERI, J.OF NERV.MENTAL DIS,1987) SIDE EFFECTS: TACHYCARDIA, ANXIETY, PALPITATIONS,ANOREXIA SCHEDULE II ON THE DEA PRESCRIPTION FORM DUE TO POTENTIAL FOR ADDICTION

DEXTROAMPHETAMINE
HORNSTEIN ET AL, 1996 : STUDIED 27 ACUTE TBI PATIENTS PLACED ON THIS AGENT DURING ACUTE REHAB 15 / 27 HAD AN IMPROVEMENT ON THE GLASGOW OUTCOME SCALE

METHYLPHENIDATE (RITALIN)
INDIRECT CATHECOLAMINE AGONIST- ACTS PRIMARILY TO INCREASE DOPAMINE ENHANCES ATTENTION, AROUSAL,INITITATION ,VIGILANCE SHORT HALF LIFE - DOSE TWICE/DAY SCHEDULE II

METHYLPHENIDATE
SHOWN TO ENHANCE ATTENTION, AROUSAL, SPEED OF PROCESSING & REDUCE ANGER IN TBI SUBJECTS IN A DOUBLE BLIND PLACEBO CONTROLLED CROSSOVER STUDY INVOLVING 19 SUBJECTS IT DID NOT HOWEVER INCREASE MOTOR SPEED OR REDUCE DISTRACTIBILITY DOSE : 0.25 MG/KG BID (WHYTE ET AL, ARCHIVES OF PM&R, 1997) SHOWN TO ENHANCE INITIATION & AROUSAL IN 2 MINIMALLY CONSCIOUS PATIENTS (LABORDE & WHYTE,J. OF HEAD TRAUMA REHAB,1997)

METHYLPHENIDATE
SHOWN TO IMPROVE ATTENTION, VIGILANCE, MOTOR PERFORMANCE & DISABILITY RATING SCORES IN 23 SUBACUTE TBI SUBJECTS BY DAY 30 IN A 30 DAY DOUBLE BLIND PLACEBO CONTROLLED STUDY (PLENGER ET AL., ARCHIVES OF PM&R,1996) IT WAS NOTED HOWEVER THAT THERE WAS NO DIFFERENCE BETWEEN THE TREATMENT GROUP AND THE PLACEBO GROUP IN TERMS OF OUTCOME MEASURES BY DAY 90 THIS SUGGESTS THE METHYLPHENIDATE IMPROVES THE RATE OF RECOVERY

METHYLPHENIDATE
SHOWN TO IMPROVE ATTENTION & THE DISABILITY RATING SCALE IN 11 ACUTE TBI SUBJECTS IN A PROSPECTIVE STUDY AT A DOSE OF 15 MG PO BID (KAELIN ET AL.,
ARCHIVES OF PM&R, 1996)

METHYLPHENIDATE
SIDE EFFECTS: TACHYCARDIA, HYPERTENSION, ANOREXIA, OVERSTIMULATION, INSOMNIA OVERALL LOWER SEIZURE INCIDENCE OBSERVED IN TBI PATIENTS WITH SEIZURE HX.WHILE ON RITALIN
WROBLEWSKI ET AL, J. CLIN. PSYCH., 1992

METHYLPHENIDATE IN TBI
DOUBLE BLIND PLACEBO CONTROLLED CROSSOVER STUDY 15 ADULTS WITH SEVERE TBI WITH METHYLPHENIDATE 0.15 MG/KG BID, AND 0.3 MG/KG BID RESULT : TREND TOWARDS IMPROVED MOOD, IMPROVED ATTENTION, LESS DISTRACTIBILITY IN STUDY SUBJECTS NO IMPROVEMENTS IN MEMORY, PROCESSING SPEED, OR SOCIAL INTERACTION NO IMPROVEMENTS IN MEMORY, PROCESSING SPEED, OR SOCIAL INTERACTION GUALTIERI & EVANS, 1988

METHYLPHENIDATE IN CHILDREN
MAHALICK ET AL, 1998 : CROSSOVER STUDY OF 14 CHILDREN AGE 5 14 WITH MILD MODERATE TBI DOSE : 0.3 MG/KG BID STATISTICALLY SIGNIFICANT IMPROVEMENTS IN VIGILANCE, PROCESSING SPEED, AND REDUCTIONS IN DISTRACTIBILITY

BROMOCRIPTINE
ERGOT DERIVATIVE MIXED DOPAMINERGIC AGONIST & ANTAGONIST PROPERTIES AT LOW DOSES, ACTS AS A PRESYNAPTIC D2 RECEPTORS AGONIST - INHIBITS DOPAMINE RELEASE A HIGHER DOSES - ACTS AS A DIRECT AGONIST AT POST SYNAPTIC RECEPTORS AUGMENTS DOPAMINERGIC FRONTAL LOBE FUNCTION DOSING : START AT 2.5 MG / DAY AND TITRATE UP **DOES NOT HAVE AN EFFECT ON AFFECTIVE LABILITY OR MOOD DISORDER POST TBI**

BROMOCRIPTINE - IMPROVES APHASIA POST TBI/STROKE

BROMOCRIPTINE- WELL DOCUMENTED TO IMPROVE APHASIA IN TBI IMPROVES FLUENCY REDUCES LATENCY OF VERBAL RESPONSES & PARAPHASIAS INCREASES NAMING ABILITY DOSAGE : START AT 2.5 MG & TITRATE UP TO 15 MG / DAY
GUPTA ET AL., NEUROLOGY, 1995 SMALL, STROKE, 1994

BROMOCRIPTINE FOR HEMISPATIAL NEGLECT

BROMOCRIPTINE 15 MG QD IMPROVED HEMISPATIAL NEGLECT IN PTS. WITH ISCHEMIC INFARCTION & TBI EFFECT REVERSED BY DOPAMINE ANTAGONIST, HALDOL
FLEET ET AL.,NEUROLOGY, 1987 ZASLER ET AL., ARCHIVES OF PM&R,1989

BROMOCRIPTINE
IN 1 CASE STUDY, BROMOCRIPTINE
DECREASED RETROGRADE AMNESIA IMPROVED VERBAL LEARNING MEMORY / DAILY RECALL IN A PATIENT WITH MEDIOBASAL FOREBRAIN INJURY (DOBKIN ET AL., ANNALS
OF NEUROLOGY, 1993)

BROMOCRIPTINE
IMPROVED FRONTAL LOBE MEDIATED COGNITIVE FUNCTION & MOTIVATION IN 11 TBI SUBJECTS
POWELL ET AL., JOURNAL OF NEUROLOGY, NEUROSURGERY, PSYCHIATRY,1996

BROMOCRIPTINE
IMPROVED EXECUTIVE FUNCTION AND INITIATION
ZAFONTE ET AL., J. OF HEAD TRAUMA REHAB, 2001

BROMOCRIPTINE-SIDE EFFECTS
NAUSEA HALLUCINATIONS/ PSYCHOSIS MOVEMENT DISORDERS ABDOMINAL CRAMPS SYNCOPE NAUSEA VOMITING CANNOT BE USED IN PTS. WITH :
UNCONTROLLED HTN **PTS WHO ARE BREASTFEEDING** THOSE WHO ARE SENSITIVE TO ERGOT ALKALOIDS SAFE FOR USE IN PREGNANCY

LEVODOPA / CARBIDOPA
SHOWN TO IMPROVE EXECUTIVE FUNCTION IN TBI PATIENTS IN PLACEBO CONTROLLED TRIALS
ZAFONTE ET AL., J. OF HEAD TRAUMA REHAB, 2001

IMPROVED STATUS OF PATIENT IN VEGETATIVE STATE MATSUDA

ET AL

LEVODOPA
SHOWN TO REDUCE NEUROGENIC FATIGUE IN 12 TBI SURVIVORS (COMMON AFFECTS 80% OF TBI PTS.) PATIENTS ALSO HAD IMPROVED ALERTNESS, CONCENTRATION, MEMORY, MOBILITY, POSTURE, SPEECH, AS WELL AS LESS SIALORRHEA & HYPOMANIA
LAL ET AL., BRAIN INJURY, 1988

LEVODOPA
DOSAGE 10/100 MG BID TID, TITRATE UP TO 25/250 MG QID IF NECESSARY SIDE EFFECTS:
HYPOTENSION / HYPERTENSION ARRYTHMIAS NAUSEA / VOMITING /ANOREXIA DYSTONIA / ATAXIA DYSKINESIA HALLUCINATIONS PARANOIA / PSYCHOSIS ORTHOSTATIC HYPOTENSION / DIZZINESS CAN ALSO TRY THE COMTAN / LEVODOPA /CARBIDOPA COMBINATION DRUG, STALEVO 200 MG PO TID

SELEGILINE
MAOI B INHIBITOR AT LOW DOSES MAOI A & B INHIBITOR AT HIGHER DOSES USED AS AN ADJUNCT IN MANAGEMENT OF PARKINSONS DISEASE - 5 MG PO BID ANECDOTAL REPORTS OF ITS SUCCESSFUL USE IN TBI PATIENTS STUDIES IN TBI PENDING, IMPROVES MEMORY/ ATTENTION IN ALZHEIMERS SUBJECTS

NIMODIPINE
CALCIUM CHANNEL BLOCKER SELECTIVE FOR CEREBRAL VESSELS PREVENTS ISCHEMIC INJURY CAUSED BY VASOCONSTRICTION AFTER SUBARACHNOID HEMORRHAGE

NIMODIPINE
SIDE EFFECTS: DECREASED BLOOD PRESSURE AND HEART RATE GASTROINTESTINAL SYMPTOMS ELEVATED LFTS

NIMODIPINE
EFFICACY IN TBI OTHER THAN THAT PRODUCED BY SUBARACHNOID HEMORRHAGE IS NOT WELL STUDIED DOSE IS 90 MG PO QD

GINKGO BILOBA
HERBAL MEDICATION FREE RADICAL SCAVENGER SUPPRESSES PLATELET AGGREGATION FACTOR INCREASES REVASCULARIZATION OF ISCHEMIC TISSUE

GINKGO BILOBA
IN NORMAL HUMANS,GINKGO INCREASES SHORT TERM MEMORY DECREASES REACTION TIME INCREASES SPEED OF INFORMATION PROCESSING POSITIVE EFFECT ON ATTENTION & MEMORY IN ALZHEIMERS & MULTIINFARCT DEMENTIA

GINGKO BILOBA
EFFECT IN TBI NOT KNOWN DOSES TYPICALLY 120-600 MG PER DAY

NEUROPEPTIDES
VASOPRESSIN IS THE MOST FREQUENTLY STUDIED IN NORMAL HUMANS,1 MG PO QD FOR TWO WEEKS IMPROVED.. INITIAL STORAGE OF ABSTRACT WORDS REDUCED RXN. TIME FOR SCREENING DIGITS EFFECTS PERSISTED AFTER DISCONTINUATION OF VASOPRESSIN

VASOPRESSIN
VASOPRESSIN TRIALS IN TBI SURVIVORS WITH POST TRAUMATIC AMNESIA INCONCLUSIVE RESULTS JENKINS ET AL., LANCET, 1981 KOCH-HENDRICKSON ET AL, LANCET, 1981

PEMOLINE
SYMPATHOMIMETIC AGENT KNOWN AS CYLERT INDIRECT ACTING CATECHOLAMINE STIMULANT SCHEDULE II DEA DUE TO ADDICTIVE POTENTIAL

PEMOLINE
PROVEN EFFECTIVE IN THE TREATMENT OF ATTENTION DEFICIT DISORDER NO EVIDENCE TO SUPPORT ITS USE IN TBI AT THIS TIME DOSE : 2-3 MG / KG OF BODY WEIGHT

TRICYCLIC ANTIDEPRESSANTS
PROTRIPTYLINE,AMITRIPTYLINE,& DESIPRAMINE IMPROVE AROUSAL & INITIATION IN CHRONIC TBI PATIENTS REINHARD ET AL., ARCHIVES OF PM&R,1996 WROBLEWSKI ET AL., BRAIN INJURY,1993

TRICYCLICS IMPROVE APHASIA POST TBI

TRICYCLICS IMPROVE LANGUAGE PERFORMANCE AFTER TBI IN CASE REPORTS ELAVIL 50 MG QHS IMPROVED SPEECH INITIATION IN 1 TBI PT. DESIPRAMINE 75 MG- INITIATION OF SPEECH 1 CASE REPORT REINHARD ET AL., ARCHIVES OF PM&R, 1996

TRICYCLIC ANTIDEPRESSANTS
IN ACUTE TBI, TRICYCLICS IMPROVE RXN. TIMES IN PTS. WITH POST TRAUMATIC AMNESIA AMITRIPTYLINE 50 MG PO QD DESIPRAMINE 50-75 MG PO QD PROTRIPTYLINE 15-50 MG PO QD MYSIW ET AL.,ARCHIVES OF PM&R,1986

AMANTADINE IN TBI
CENTRAL DOPAMINERGIC AGONIST MECHANISM OF ACTION: UNCLEAR USED FOR TREATMENT OF EXTRAPYRAMIDAL SYMPTOMS SECONDARY TO ANTIPSYCHOTICS INFLUENZA A FATIGUE IN MS PATIENTS PARKINSONS DISEASE START AT 50 MG / DAY AND TITRATE UP BY 100 MG / DAY WEEKLY TO MAX DOSE OF 400 MG / DAY

AMANTADINE
IN TBI, AMANTADINE IMPROVES..
FATIGUE VISUAL ATTENTION SPEED OF INFORMATION PROCESSING CONCENTRATION ENHANCED PARTICIPATION IN THERAPY REDUCED DISTRACTIBILITY ALSO IMPROVES :
ABULIA MUTISM ANHEDONIA PERSEVERATION AGITATION

AMANTADINE THE EVIDENCE

IMPROVEMENT IN COMA AND NEAR COMA SCORE AND AROUSAL IN A CASE STUDY OF 1 SEVERELY BRAIN INJURED SUBJECT
ZAFONTE ET AL., BRAIN INJURY, 1998

AMANTADINE THE EVIDENCE

IMPROVEMENT IN VISUAL ATTENTION, SPEED OF INFORMATION PROCESSING, CONCENTRATION
ANDERSSON ET AL, TIDSSKR NORS LAEGEFOREN,1992

3 DAY COURSE OF AMANTADINE REDUCED MORTALITY & IMPROVED GCS SANIOVA ET AL, J. NEURAL TRANSMISSION,
2004

AMANTADINE THE EVIDENCE

GAINS IN
ATTENTION, CONCENTRATION REDUCED DISTRACTIBILITY INCREASED RESPONSIVENESS ENHANCED PARTICIPATION IN THERAPIES
NICKELS ET AL., BRAIN INJURY,1994

AMANTADINE - THE EVIDENCE

CASE REPORTS: AMANTADINE REDUCED POST TRAUMATIC AGITATION WHEN OTHER AGENTS FAILED
NICKELS ET AL., BRAIN INJURY,1994 CHANDLER ET AL., BRAIN INJURY,1988

AMANTADINE
REDUCED NEUROGENIC FATIGUE IN TBI PATIENTS
NICKELS ET AL., BRAIN INJURY,1994

AMANTADINE THE EVIDENCE

AMANTADINE IN DAI : DOUBLE BLIND PLACEBO CONTROLLED CROSSOVER STUDY OF 35 PTS. WITH DAI AMANTADINE 200 MG / DAY FOR 6 WEEKS FINDINGS : IMPROVEMENTS IN MMSE, FIM, DRS, GOS
MEYTHALER ET AL, J. OF HEAD TRAUMA REHABILITATION, 2002

AMANTIDINE THE EVIDENCE

KRAUS & MAKI, 1997AMANTIDINE 400 MG / DAY TO 6 PATIENTS IMPROVEMENTS NOTED IN : ALERTNESS ATTENTION MOTIVATION EXECUTIVE FUNCTION DIMINISHED LABILITY DECREASED IMPULSIVITY

AMANTADINE-SIDE EFFECTS
WELL TOLERATED AT DOSES LESS THAN 400 MG PER DAY ADVERSE EFFECTS:
INSOMNIA/ IRRITABILITY DIZZINESS ANXIETY/ANOREXIA LOWERS SEIZURE THRESHOLD - MAY PRECIPITATE PSYCHOSIS / MANIA / HALLUCINATIONS LIVEDO RETICULARIS

MODAFINIL
MARKETED TO TREAT NARCOLEPSY & FATIGUE SECONDARY TO ..
MS PARKINSONS SLEEP APNEA NARCOTICS

MODAFINIL
MECHANISM OF ACTION IS UNCLEAR MAY ACT BY INCREASING NOREPINEPHRINE LEVELS IMPROVES AROUSAL & ALERTNESS IN NON INJURED SUBJECTS ELOVIC HAS SUGGESTED THAT THIS AGENT MAY BE USEFUL IN UNDERAROUSAL STATES POST TBI DOSE : 100 400 MG PO Q AM

MODAFANIL
TEITELMAN, 2001 STUDIED 10 TBI OUTPATIENTS IN AN OPEN LABEL STUDY WITH 100 400 MG / DAY SUBJECTS HAD NON PENETRATING BRAIN INJURIES & EXCESSIVE DAYTIME SLEEPINESS SUBJECTS DESCRIBED IMPROVEMENTS IN SLEEPINESS AND IMPROVEMENTS IN ATTENTION TREATMENT INTOLERANCE DEVELOPED IN SOME PATIENTS IN THE FORM OF EMOTIONAL INSTABILITY WHILE ON THE DRUG

MODAFINIL
SIDE EFFECTS:
HEADACHE GASTROINTESTINAL DISTURBANCES ANXIETY HALLUCINATIONS CONTRAINDICATED IN PTS. WITH ANGINA AND RECENT MI

MEMANTINE
LOW AFFINITY NMDA RECEPTOR ANTAGONIST FDA APPROVED FOR TREATMENT OF COGNITIVE DECLINE IN ALZHEIMERS NO STUDIES OF THIS AGENT IN TBI TO DATE

ATOMOXETINE (Strattera)
NEW AGENT USED FOR ADHD IN CHILDREN NOT STUDIED IN TBI YET HIGHLY SELECTIVE INHIBITOR OF NOREPINEPHRINE REUPTAKE WEAK DOPAMINERGIC EFFECT 40 MG PO DAY IS STARTING DOSE INCREASE TO 80 MG / DAY SIDE EFFECTS : INSOMNIA, MANIA, ANOREXIA

TRAZADONE
HETEROCYCLIC ANTIDEPRESSANT USED TO RESTORE NORMAL SLEEP/WAKE CYCLES IN TBI PTS. BLOCKS SEROTONIN REUPTAKE, INCREASES SEROTONIN IN RAPHE NUCLEUS- AREA WHICH CONTROLS SLEEP & MOOD START IT AFTER COMPILING A SLEEP DIARY DOSE 50 100 MG PO Q HS

AGENTS TO IMPROVE THE SLEEP/WAKE CYCLE

NEFAZODONE (SERZONE) 100-200 MG PO Q HS REMERON (MIRTAZIPINE) 15-60 MG PO QHS LESS FREQUENTLY USED IN TBI FOR RESTORATION OF THE SLEEP/WAKE CYCLE

THANKS FOR YOUR ATTENTION!