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The levodopa response duration decreases over time, and many patients eventually develop wearing-off fluctuations. Wearing off occurs during the day, characterized by a gradual return of parkinsonian symptoms before the next dose takes effect, usually one to three hours after the last dose. Initially, a practical approach would be to give smaller and more frequent levodopa doses. However, at some point this will no longer be effective. Use of Sinemet CR can be helpful in reducing clinical fluctuations because levodopa is slowly released from a special matrix, producing a more sustained clinical effect. Adding a dopamine agonist such as bromocriptine or pergolide in combination with levodopa can help improve wearing-off effects. These agents should be initiated at subtherapeutic dosages and then very gradually increased over a period of weeks to therapeutic doses. This gradual buildup will help reduce adverse effects such as nausea, hallucinations, hypotension, and sedation. Bromocriptine can be initiated at 1.25 mg twice daily and then gradually increased, according to response, to a usual dose of 10-25 mg daily (some require 50-75 mg daily). Pergolide can be initiated at a dose of 0.05 mg daily and then can be titrated slowly over a period of weeks to a usual dose of 2-3 mg (5 mg daily is the maximum). As the dose of the dopamine agonist is increased, the levodopa dose is usually lowered to reduce dopaminergic toxicity. Another treatment option is amantadine, which can prolong the action of levodopa and produce some mild improvement in wearing-off effects. However, amantadine can increase the risk of cognitive impairment in the elderly, and dosages should be adjusted in patients with impaired renal function. Initially, amantadine can be given at a dose of 100 mg daily for one to two weeks before attempting to increase the dose to 100 mg b.i.d. Doses greater than 200 mg daily are usually not recommended in the elderly. Selegiline is another alternative. Selegiline increases the duration of levodopa effects by preventing its breakdown, and it has been used successfully to improve wearing-off effects.3,23 When selegiline is added to levodopa, it should be started at a low dose and slowly increased (5-10 mg per day is usually effective) to minimize side effects.1 The addition of selegiline can exacerbate the side effects of levodopa and, consequently, a reduction of the levodopa dose by 10%-30% is usually necessary. The psychiatric side effects of selegiline may not be tolerated by the elderly. For those patients who develop severe wearing-off fluctuations that do not respond to the above measures, the use of liquid carbidopa/levodopa is another option. One study showed benefits when this solution was taken at regular intervals.24 Preparing a carbidopa/levodopa solution is relatively easy and inexpensive, but the product must be prepared on a daily basis since it is stable for only 24 hours.20 Use of this solution sidesteps problems with gastric emptying because it does not need to be digested before being emptied into the small intestine. Another advantage to the solution is that it provides more flexibility in titrating the levodopa dose. The solution can be prepared by grinding up 10 tablets of carbidopa 25 mg/levodopa 100 mg along with 2g of ascorbic acid, and adding it to 1 liter of tap water to produce a solution of 1 mg/mL levodopa, 0.25 mg/mL carbidopa, and 2 mg/mL ascorbic acid. The ascorbic acid helps to prevent the oxidation of levodopa.24 Some clinicians recommend dissolving the tablets in Tang fruit drink as a way to add ascorbic acid to the solution.25 The solution must be shaken well before use. The presence of black particles indicates that levodopa has broken down, and a solution with this type of precipitate should be discarded. --- Outgoing mail is certified Virus Free. Checked by AVG anti-virus system (http://www.grisoft.com). Version: 6.0.408 / Virus Database: 230 - Release Date: 10/24/2002 ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn