Neuropsychopharmacology Update : 2012

09.12.2012 1430-1545

Gregory J. O’Shanick, MD

President & Medical Director, Center for Neurorehabilitation Services, Richmond, VA

Past Chair, Board of Directors & Medical Director Emeritus, BIAA

OVERVIEW

Rationale underlying the use of centrally acting medications in individuals following brain injury

Roles of neurotransmitters, hormones and cofactors with specific attention to those that influence behavior and cognition

Strategies for medication trials

Misuse of these agents

Tolerance difficulties and common side effects

DISCLAIMER

Currently a paid consultant for Avanir, a pharmaceutical manufacturing company.

Has also been a paid consultant to other

pharmaceutical companies in the past. Medication strategies in this presentation will

include discussion of off-label uses for conditions other than those specifically approved by the FDA in the package insert of the product.

The neuron is the basic unit of brain function

10,000 neurons can fit in a

space the size of the eye of a needle (1mm)

Mature neurons have

specialized functions Neurons are supported by a

“skeleton” (glial cells) Electrical activity triggers

neurotransmitter release

Neurons interact through the release of neurotransmitters

Powering the neuron

Mechanics of traumatic brain injury

“cell suicide”

Neurotransmitter changes after TBI

Activity correlates with better outcome

Increased catecholamine activity correlates with better outcome

Decreased serotonergic activity noted in frontal contused/agitated

Decline in catecholamine activity over time

Neuropharmacology and Brain Injury

Predicated on studies in other populations

Few large, well-designed RCTs in brain injury

Uses are “off label”

Treatment of co-morbid or pre-morbid conditions

Third party reimbursement problems

Patient assistance program complexities

Successful treatment requires that the following must be stable:

Sleep

Pain

Nutrition

Hydration

Exercise

Classes of agents used in brain injury

Anticonvulsants

Antispasticity agents

Antidepressants

Antianxiety agents

Antipsychotics

Antiparkinsonian agents

Anti-impulsivity/Antimanic agents

Cognitive enhancers

Anticonvulsants: Types and Target Symptoms

• Tegretol, Carbatrol (carbamazepine)

• Trileptal (oxcarbazepine)

• Dilantin (phenytoin)

• Depakote (valproic acid)

• Neurontin (gabapentin)

• Klonopin (clonazepam)

• Lamictal (lamotrigine)

• Topamax (topiramate)

• Keppra (levetiracetam)

• Zonegran (zonisamide)

• Lyrica (pregabalin)

• Vimpat (lacosamide)

• Phenobarbital

• Posttraumatic seizures

• Epilepsy spectrum disorder

• Posttraumatic headache

• Intermittent explosive disorder

• Impulsivity/ mania

• Positive psychotic symptoms

• Kluver-Bucy Syndrome

• Chronic pain syndromes

Antispasticity agents: Types and Target Symptoms

• Dantrium (dantrolene)

• Flexeril (cyclobenzaprine)

• Baclofen (lioreseal)

• Robaxin (methocarbamol)

• Skelaxin (metaxolone)

• Soma (carisoprodol)

• Zanaflex (tizanidine)

• Botox (botulinum toxin)

• Increased muscle tone

• Acute muscle spasm

• Headache due to muscle tension

Antidepressants: Types and Target Symptoms

• Tricyclics: imipramine, amitriptyline, nortriptyline, desipramine, protriptyline, clomipramine, doxepin, amoxapine

• Tetracyclics: maprotiline (Ludiomil) • SSRI: fluoxetine (Prozac), sertraline

(Zoloft), fluvoxamine (Luvox), paroxetine (Paxil), trazodone, citalopram (Celexa), escitalopram (Lexapro), vilazodone (Viibryd)

• SNRI: venlafaxine (Effexor), duloxtine (Cymbalta), desvenlafaxine (Pristiq)

• Bupropion (Wellbutrin, Zyban) • Mirtazapine (Remeron) • Milnacipran (Savella) • MAO Inhibitors: phenelzine (Nardil),

tranylcypromine (Parnate) • Nutriceuticals: tetrahydrofolate

(Deplin)

• Neurovegetative symptoms: IN SAD CAGES

• Post traumatic stress disorder

• DIMS

• Enuresis

• Explosive episodes

• Chronic pain syndromes

• Migraine prophylaxis

• Pseudobulbar affect

Dextromethorphan/quinidine

Antianxiety agents: Types and Target Symptoms

• Benzodiazepines: lorazepam (Ativan), diazepam (Valium), alprazolam (Xanax), chlordiazepoxide (Librium), chlorazepate (Tranxene), clonazepam (Klonopin), temazepam (Restoril), flurazepam(Dalmane)

• Buspirone (Buspar)

• Hydroxyzine (Atarax, Vistaril)

• Initial insomnia

• Anticipatory anxiety

• Spasticity

• Seizure

• Acute aggressive behavior

• Chronic agitation (buspirone)

• Ethanol detox (except buspirone)

Psychostimulants: Types and Target Symptoms

• methylphenidate (Ritalin, Concerta, Metadate, Daytrana)

• d-amphetamine (Dexedrine)

• dexmethylphenidate (Focalin)

• amphetamine salts (Adderall)

• lisdexamfetamine (Vyvanse)

• atomoxetine (Strattera)

• guanfacine (Intuniv)

• Decreased attention/concentration

• Fatigue

• Narcolepsy / posttraumatic sleep disorder

• Apathy/amotivation

Anti-impulsivity (antimanic) agents Types and Target Symptoms

• Lithium

• clonidine (Catapres)

• propranolol (Inderal)

• carbamazepine (Tegretol)

• valproic acid (Depakote)

• lamotrigine (Lamictal)

• Cyclic mood disorders

• Refractory mood disorders

• Aggressive behavior

• Interictal behavior disturbance

Cognitive enhancers: Types and Target Symptoms

• tacrine (Cognex)

• donepezil (Aricept)

• rivastigmine (Exelon)

• galantamine (Razadyne)

• memantine (Namenda)

• Gingko biloba

• Estrogen

• Omega 3 Fatty Acids

• Tetrahydrofolate/cyanocobalamin (Cerefolin)

• Alzheimer’s disease

• Vascular dementia

• Hypoxic brain injury

• Traumatic brain injury

? Elders

? APOE4

Antipsychotics: Types and Target Symptoms

• clozapine (Clozaril)

• olanzepine (Zyprexa)

• quetiapine (Seroquel)

• phenothiazines (Thorazine,

Mellaril, Compazine, Trilafon, Phenergan, Stelazine, Prolixin)

• buterophenones (Haldol, Risperdal, Geodon)

• aripiprazole (Abilify)

• Vomiting

• Analgesic potentiation

• Decreased GI motility

• Positive psychotic symptoms

• Agitation / aggression - short term use

Antiparkinson agents: Types and Target Symptoms

Dopamine agonists: bromocriptine (Parlodel) pergolide (Permax) ropinirole (ReQuip) pramipexole (Mirapex)

DA production enhancers:

L-DOPA/carbidopa

DA potentiators:

amantadine, selegiline, rasagiline

Anticholinergics:

trihexyphenidyl (Artane),

benztropine (Cogentin), diphenhydramine (Benedryl)

• “Classic” Parkinsons Syndrome

• Initiation /amotivation

• Dysphagia

• Attention and concentration

• Fatigue

• cognitive endurance

• Drooling

• Vestibular dysfunction

• Tactile defensiveness

• Coma

Therapeutic trial: General concepts

Adequate drug available to the CNS

“Start low and go slow”

Duration appropriate to half-life & CNS effect

Monitor target symptoms (? blinded)

Change only one variable at a time

If trial (+), withdraw agent to assess if spontaneous remission or drug effect

Thank you and remember to support the

Brain Injury Association of America and its local affiliates!!