PRACTICAL GUIDELINES FOR THE DRUG-TREATMENT OF PARKINSONS-DISEASE

A number of drugs are available for the treatment of the symptoms of Parkinson's disease. Because monoamine oxidase B (MAO-B) inhibitors may have a neuroprotective action, starting treatment of de novo patients with these agents may be the best approach. If this therapy is not sufficient to improve symptoms, addition of a levodopa preparation combined with a peripheral dopa decarboxylase inhibitor is the next treatment choice. Treatment can also be started with levodopa, a dopamine agonist, amantadine or an anticholinergic agent. When the treatment is started with a drug other than levodopa, levodopa should be added if the response to that drug is not satisfactory. Daily levodopa dosage should be titrated carefully according to the severity of the disease and the degree of patient satisfaction with this therapy. Successful long term drug treatment of Parkinson's disease requires meticulous management of various problems that may arise from therapy. Among these, levodopa-related motor fluctuations are the most frequent and important problem. Many approaches are now available to reduce the severity and frequency of motor fluctuations. such as the use of controlled release levodopa formulations, concomitant use of a dopamine agonist and/or a MAO-B inhibitor, frequent administration of levodopa, and administration of a protein redistribution diet. Although though still at the stage of preliminary clinical investigation, catechol-O-methyl-transferase inhibitors appear to have promise for reducing the severity and incidence of levodopa-induced motor fluctuations. On-off fluctuations to levodopa are still difficult to treat satisfactorily. Clozapine may suppress levodopa-induced hallucinations and delusions, without significant worsening of Parkinsonism. A mild degree of drug-related dyskinesias usually does not require special treatment. For more severe dyskinesias 2 approaches can be taken. First, a reduction of the maintenance dose of levodopa until the severity of dyskinesias becomes mild enough to be tolerated. Secondly, the concomitant use of a selective dopamine D2 receptor antagonist, such as tiapride, if a reduction of levodopa dosage worsens Parkinsonism. However, tiapride may partially block the anti-Parkinsonian effects of levodopa. The most common adverse effects of other anti-Parkinsonian drugs are gastrointestinal [selegiline (deprenyl), dopamine agonists] and psychiatric (dopamine agonists, amantadine, anticholinergics) effects. Pleuropulmonary change and retroperitoneal fibrosis are rare complications of long term treatment with bromocriptine, and a controlled release formulation of the drug has been developed in an attempt to reduce the overall incidence of adverse effects. Because of their common adverse effects, anticholinergics should be used with care and are contraindicated in patients with narrow angle glaucoma and/or prostate hypertrophy with dysuria.