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Stroke Rehabilitation Medication Management for TBI Jun Zhang, MD, FAAPMR Assistant Professor Stony Brook University St. Charles Hospital “My brain? That's my second favorite organ.” Facts 1.8 million visits annually to the ED Over 289,000 patients were hospitalized annually for injuries related to a TBI. Where Is the Mango Princess Where Is the Mango Princess Cathy, Alan, and seven-year- old daughter Kelly from Philadelphia, won a raffle at Kelly’s school auction for a week long vacation at a remote location called Bob's Lake in Kingston, Ontario. Where Is the Mango Princess The vacation went pretty miserably, and on the last day they were ready to head home. Alan took a boat trip to take away dirty laundry and garbage from their cabin. On the way, a speedboat T-boned Alan's boat, knocking him in the head and causing massive bleeding and bruising. Kelly was in the boat and witnessed the accident. Where Is the Mango Princess The speedboat knocking him in the head and causing massive bleeding frontal lobe, TBI, DAI, or diffuse axonal injury Where Is the Mango Princess 44 YO left hand white male, with no significant PMH, s/p boat accident on July 1, 1996, with LOS then grand mal seizure, induced coma then intubated for airway protection. Airlifted to Kingston General Hospital for intensive care. Airlifted to the Hospital of the University of Philadelphia. Magee Rehabilitation Center. Day hospital Home. Where Is the Mango Princess Hyper-arousal/agitation What to do? First: environment change Second Medicine Beta-blockers Buspirone Psychotropic medications Benzodiazepines Amantadine Lamotrigine Beta Blocker Beta Blocker Benzodiazepines Benzodiazepines were first recognized in the 1950s for their ability to produce "taming" without apparent sedation in animal experiments. The benzodiazepines were recognized as comparatively problem-free compared to the barbiturates, and rapidly replaced earlier sedatives. Benzodiazepines exert their principal pharmacodynamic effect via CNS GABA receptors, potentiating the effects of endogenous GABA, the main inhibitory neurotransmitter. Most benzodiazepines are off patent currently, and are not actively promoted by pharmaceutical representatives. Benzodiazepines Benzodiazepines Diazepam (Valium) and clorazepate (Tranxene) have fast onsets of action and usually start working within 30 to 60 minutes. Oxazepam (Serax) has a slow onset, and lorazepam (Ativan), alprazolam (Xanax), and clonazepam (Klonopin) have intermediate onsets of action. Clorazepate (Tranxene), midazolam (Versed), and triazolam (Halcion) are short-acting agents with durations of action of 3 to 8 hours. Alprazolam (Xanax), lorazepam (Ativan), estazolam (Prosom), and temazepam (Restoril) are intermediate-acting agents with durations of action of 11 to 20 hours. Chlordiazepoxide (Librium), clonazepam (Klonopin), diazepam (Valium), flurazepam (Dalmane), and quazepam are long-acting agents with duration of action of 1 to 3 days. Benzodiazepines Slows motor recovery, induced hemiparesis (animal model). Paradoxical agitation. Shorter Acting for acute mania and psychiatric emergencies: . Midazolam (versed) . Lorazepam (ativan) Not recommended for long term agitation treatment due to interference with cognitive function and sedation Benzodiazepines Almost always, hinder cognition recover Typical Antipsychotics D2 antagnoism Rapid onset Extrapyramidal ssx, paradoxical akathesia, PTA, longer motor recovery, 2nd parkinsonism etc.. Such as: Haldol …The typical agents, in both human and animal studies, have been shown to cause a decline in cognitive performance (verbal ability, memory, learning, attention, spatial ability…..once the medication was stopped, cognition improved) Stanislav et al, Brain Injury 1997, p335-41 Atypical Antipsychotics D2 and 5-HT not quite sure, but decreased unwanted effects of typical antipsychotics. Such as: . Risperidone (Risperdal) . Quetiapine (Seroquel) . Buspirone(Buspar) . Aripiprazole (Abilify) . Ziprazadone (Geodon) . Clozapine (Clozaril) Atypical Antipsychotics Risperidone (Risperdal) advantage of extensive clinical experience, availability in multiple forms, and lower cost generic versions; associated with somewhat greater risk for EPS (extrapyramidal symptoms) , weight gain, and prolactin elevation than other atypicals. Atypical Antipsychotics Quetiapine (Seroquel) The usual adult starting dose 25 mg twice daily, followed by titration at the rate of 25 to 50 mg/day to a total dose of 300 to 600 mg/day. more effective in long-term maintenance therapy for schizophrenia but carries greater risk of metabolic side effects. particularly low incidence of EPS and is preferred for patients with movement disorders. Atypical Antipsychotics Buspirone(Buspar) Aripiprazole (Abilify) Ziprazadone (Geodon) Clozapine (Clozaril) Life-threatening agranulocytosis has been reported during the first six months of treatment. Routine CBC monitoring required. Buspirone Contraindications/Cautions . hypersens. to drug/class/compon. MAO inhibitor use w/in 14 days caution if hepatic impairment caution if renal impairment Amantadine NMDA agonist Lamotrigine SIDE EFFECTS: dizziness, somnolence, headache, double vision, blurred vision, nausea, vomiting, and rash. Which drug class has the best evidence for its effectiveness in the treatment of agitation associated with acquired brain injury? (a) Anticonvulsants (b) Anxiolytics (c) Antipsychotics (d) Beta blockers Hypo-arousal Incidence : unknown Treatment: First evaluate meds Then, possible more meds Amantadine NMDA agonist Bromocriptine Agonist at dopamine D2 receptors and serotonin receptors. inhibits the release of glutamate, by reversing the glutamate GLT1 transporter. Research on vegetative state : small sample size Sinemet (levodopa/carbidopa) Research on vegetative state patient, increase dose until plateaued, with some improvement. Zolpidem GABA inhibitor Setraline SSRI Small studies Modafinil Unknown mechanism . Pramipexole D2- 4 receptor agonis, Similar effect as amantadine. Attention and Slow Processing Speed Prevalence: 40 -60 % at 1-3 months after TBI also found long term effect What to do? Speech Therapy, Occupational Therapy, Psychology Medicine Target Norepinephrine, Acetylcholine and Dopamine pathway Methylphenidate Ritalin Dopamine and norepinephrine reuptake inhibitor Multiple studies showed beneficial Caution: side effects such as hyperactivity, aggression , psychosis, arrhythmias or psychogenic dependence.. Donepezil Aricept reversible acetylcholinesterase inhibitor Small study showed beneficial Bromocriptine Agonist at dopamine D2 receptors and serotonin receptors. inhibits the release of glutamate, by reversing the glutamate GLT1 transporter. Research on pilot showed no difference on attention. Other Atomoxetine: a selective Norepinephrine reuptake inhibitor, no evidence Amantadine : nuh Citicoline: nuh… Sleep Sleep Diet and life style: exercise, rest and sleep hygiene Avoid naps during the day Keep regular sleep schedule (sleep log) Meds: . Non Benzodiazepine: zoldipem, zalepon . Seratonergic agent: Trazodone . Melatonin Antidepressants Depression and emotional lability Cognitive therapy and neurorehabilitation. SSRI recommended. Spasticity Spasticity Baclofen: GABA-B receptor agonist Tizanidine: centrally acting alpha-2 adrenergic agonist Dantrolene: inhibits release of calcium in the sarcoplasmic reticulum of skeletal muscle Gabapentin Other: intrathecal baclofen, Botox etc… Back to the story Alan regained most of his abilities. He returned to part- time work as bank trust officer, he could attend plays and parties, and in most areas he was able to compensate for his disability. Where Is the Mango Princess Jun Zhang, MD St. Charles Hospital 200 Belle Terre Rd, E140, Port Jefferson, NY 11777 Tel: (631) 474 - 6879 Email: [email protected].
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