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1. Drugs that may have a neuroprotective effect

Monoamine oxidase (type B) inhibitor

selegiline 5 mg, bid (breakfast and lunch) $2.71/day

2. In patients with early mild disease who have predominant tremor
i. Anticholingerics

trihexyphenidyl 2 mg, tid;increase by 2 mg, tid weekly until benefit or side effects $0.03/day

or benztropine mesylate 2 mg, tid $0.05/day

or procyclidine 2.5 mg, tid; increase to 5 mg, tid and hs $0.08-0.10/day

OR

ii. Dopamine-releasing agent

amantadine 100 mg, bid; increase as necessary to maximum of8 tablets/day $1.11-4.44/day

2. In patients with more severe disease, levodopa preparations
i. Standard release

levodopa/carbidopa 100 mg/25 mg, 0.5-1 tablet once daily; increase slowly to 1 tablet bid or tid; maximum 8 tablets/day $0.19-3.03/day

or levodopa/benserazide 100 mg/25 mg, 0.5-1 tablet once daily; increase slowly to 1 tablet, bid or tid; maximum 8 tablets/day $0.21-3.36/day

or ii. Controlled release

levodopa/carbidopa CR 200 mg/50 mg, 0.5-1 tablet bid; increase as necessary to maximum of 5 tablets/day, divided tid to qid $0.52-5.28/day

Second-line therapies:

1. To minimize the "wearing-off" and "on-off" responses with levodopa therapy, add to levodopa preparations

i. Catechol-O-methyltransferase (COMT) inhibitor

tolcapone 100 mg, tid; give first dose with first dose of the day of levodopa/benserazide or levodopa/carbidopa and subsequent doses 6 and 12 h later; titrate to 200 mg, tid $4.92-9.84/day

or ii. Dopamine agonist

pergolide 0.05 mg tid; increase by 0.1-0.15 mg/day every 4 days to maximum of 5 mg/day $0.74-15.53/day

or ropinirole 0.25 mg, tid; for first 4 weeks titrate up by weekly increments of 0.25 mg per dose; after 4 weeks increase by weekly increments of 0.5-1.0 mg per dose to maximum of 8 mg tid $0.75-8.00/day

or bromocriptine 1.25 mg, tid; increase by 1.25-2.5 mg/day to maximum of 20 mg/day $1.16-6.16/day

Additional instructions and notes

-Anticholinergics are contraindicated in older patients (over 65 years old) or in patients with pre-existing cognitive disturbances.

-Drug-related complications (dyskinesias and fluctuations in response) are more frequent after a patient has been treated for 2-5 years.

-Despite initial improvement, levodopa’s efficacy deteriorates after 3-5 years of treatment. Reserve or delay treatment until the patient’s symptoms are impairing activities of daily living or quality of life.

-Using controlled-release levodopa or dopamine agonists may reduce fluctuations ("on-off") or dyskinesias.

-Doses of levodopa should be adjusted downward once a therapeutic effect has been achieved with dopamine agonists or a COMT inhibitor.

-Monitor patients for postural hypotension when increasing anti-Parkinson’s drugs.

-Adding selegiline to levodopa increases mortality.

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