RISK FACTORS: Unknown in the idiopathic disease, Association between smoking and increased caffeine intake and reduced risk for Parkinson disease has been reported
GENERAL MEASURES
• Drugs have therapeutic and toxic effects
• Acute worsening may indicate depression, non-compliance or supervening illness
• Course is progressive with or without drugs. Life-long therapy directed toward symptom control - treat disability
• Investigate for drug-induced cause; if found, discontinue drug. Symptom resolution may take weeks to months.
• Physical, occupational and speech therapy
• Physical limitations require adjustments in the home, e.g., special chairs, elevated toilet seat, eating utensils,
dressing oneself
SURGICAL MEASURES
• Adrenal medullary transplants, fetal midbrain with substantia nigra neurons - unproven
• Thalamotomy - akinesia
• Stereotactic pallidotomy - akinesia
• Deep brain stimulation subthalamic nucleus - dyskinesia, tremor response 88%; may worsen pre-existing
psychiatric disorders; less (off) problems, less (on) dyskinesias, and 50% reduction of medications
ACTIVITY Maintain activity to whatever degree possible; use cane for walking
DIET
• Small frequent meals if difficulty in eating
• High liquid intake important; high bulk foods
• Reduced protein diet is unnecessary
DRUG(S) OF CHOICE
. Levodopa-carbidopa (Sinemet): may be initial drug of choice in older patients with more severe symptoms;
although neuro-vegetative symptoms such as speech disorders and falls are resistant to levodopa
. Sinemet SR 50-200 (start with 1/2 tab) qid after food. Increase by 100 mg levodopa per day until desired effect or side effects occur. If early morning symptoms, add Sinemet 25-100 immediate release one half hour before arising.
. If switching to the SR, increase daily dose by 25%
. Add agonist if wear off or dyskinesia appears or when 800-1000 mg levodopa SR per day being taken
. Dopamine agonists. Low potency; long half-life; reduces wearing-off effects of levodopa. Add when levodopa > 500 mg/day. early monotherapy may reduce levodopa use and long-term effects. May be initial drug of choice in younger patients with milder symptoms. May slow progression of the disease vs. L-Dopa.
. Bromocriptine - start with 1.25 mg qd or bid
. Pergolide - 0.05 mg/d for 2 days and increase by 0.1 mg/d q 3 days x 12 days. If higher doses needed,
then increase by 0.25 mg q 3 days. Mean dose is 3 mg.
. Pramipexole non-ergoline 0.125 mg tid, max 4.5 mg/day; useful for drug-resistant tremor
. Ropinirole non-ergoline. 0.25 mg tid, max 24 mg/day
. Titrate the levodopa-carbidopa combination downward as these agents are added such that 1 mg of
bromocriptine equals 10 mg of levodopa and 1 mg of pergolide equals 10 mg of bromocriptine
. MAO inhibitors. Blocks metabolism of dopamine. May be neuro-protective. Added to levodopa to diminish
motor fluctuations.
. Selegiline 5 mg - start with 1/2 tab qAM and 1/2 q noon; increase to 5 mg bid. If add to levodopa-carbidopa,
lower dosage 20%.
. Anticholinergics. For tremor and rigidity in early stages or as an adjunct (30% improvement in 50% of patients).
Not recommended for patients > age 65.
. Trihexyphenidyl (Artane): 1 mg/day, increase by 2 mg every 3 days until 6-10 mg/day
. Benztropine (Cogentin): 1-2 mg/day. Start with 0.5 mg/day and increase slowly by 0.5 mg every 6 days.
Maximum 6 mg/day.
. Amantadine, mode of action unknown
. Similar to anticholinergics; improves bradykinesia and rigidity; rapid onset 48-72h
. Synergistic with L-dopa; reduces dyskinesia
. 100-200 mg/day
. COMT inhibitor
. Reduces peripheral metabolism of levodopa permitting increase brain concentration
. Use as adjunct to L-dopa as in dopamine agonists
. May decrease motor fl uctuation in late stage disease and reduce early wearing off of levodopa, requires
fewer daily doses of levodopa
. Tolcapone - 100 mg tid, max 1200 mg/day
. Entacapone - 100 mg tid, max 1200 mg/day
Precautions:
. L-dopa/carbidopa - late effects
. Time related dosage problems occur in 50% of patients in 4-5 years
. Dyskinesias probably secondary to receptor hypersensitivity.
- Inter dose dyskinesia: occurs at peak level of drug 2 hours after immediate release form, limb choreoathetosis and grimacing; change to sustained release, reduce levodopa dose plus add agonist or
clozapine 100-200 mg.
- Diphasic dyskinesia: mobile dystonia of limbs occurs as the dose is rising and falling; increase individual dose or subcutaneous apomorphine pulses.
- Off period dyskinesia: may begin as early morning dystonia (foot); reduce inter-dose interval or switch to sustained release or agonist
. Wear-off phenomena: usually occurs 3-4 hours after last dose. Usually fi rst sign of drug-response problems caused by increased severity of nigral degeneration. Use sustained release form with an agonist or selegiline.
. On/off phenomena: 15-20% of patients develop severe fl uctuation of response. Long-term high dose
levodopa may be cause. Try low protein diet, slow release preparations, continuous subcutaneous infusions, or enteral infusion into duodenum. Also can decrease dose until on-off phenomena disappears and then restart drug. COMT inhibitors increase on time and reduce off time
. Hourly liquid preparation - 10 tablets 25-100 plus 2g ascorbic acid crystals in 1L of tap water; 75 mL in AM, then 35-50 mL/hr
. Freezing: find a visual clue to step over or counting numbers in head
. Psychiatric side effects: confusion, hallucinations (well-formed visual or auditory) paranoia, nightmares.
If mainly at night, reduce last evening dose or try clozapine.
. Agonists
. Somnolence (27%), nausea, nightmares, agitation, orthostatic hypertension, hallucinations (17%), edema (14%)
. Raynaud phenomena in doses > 30 mg/day, edema, hypertension, worsening CHF
. If stopped abruptly, can result in a syndrome resembling neuroleptic malignant syndrome
. MAO inhibitor: Anxiety/sleep disturbance
. Anticholinergics: Confusion, constipation, urinary retention, dry mouth and glaucoma
. Dopamine release stimulator: Confusion, hallucinations, edema, livedo reticularis, and worsening CHF
ALTERNATIVE DRUGS
• Tricyclic antidepressants for night time sedation and associated depression (50% of patients with Parkinson)
• Antioxidants or vitamin E have shown no definite benefit
• Selective COMT inhibitors
• Apomorphine as agonist or for freezing (use limited by adverse effects [vomiting] and need for parenteral
administration)
• Clozapine: 70-200 mg/day can suppress frequency of dyskinesia and increase on time; also useful for hallucinations.
Side effects include sedation and sialorrhea, and most serious, agranulocytosis. Use 50 mg or less per day for drug-induced psychosis.
• Donepezil 5-10 mg/day well tolerated, improved cognitive impairment
• Modafinil 100-200 mg q AM may improve excessive daytime sleepiness
PATIENT MONITORING Life-long for medication adjustment and physical therapy
PREVENTION/AVOIDANCE Avoid drugs known to cause tardive dyskinesia, such as: Fluphenazine,
perphenazine, prochlorperazine, thiopropazate, trifl uoperazine, promazine, thioridazine, haloperidol,
droperidol, benperidol, fluspirilene, pimozide, trifluperidol, chlorprothixene, clopenthixol, thiothixene
POSSIBLE COMPLICATIONS Dementia, depression, aspiration pneumonia, falls, freezing, dyskinesias; also associated with a twofold increase risk of death
EXPECTED COURSE/PROGNOSIS
• More rapid progression: Older at disease onset; dementia
• Milder disease, the predominant feature is tremor