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Ropinirole Recommended as Initial Treatment for Parkinson's Disease

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WESTPORT, May 18 (Reuters Health) - Treatment of early Parkinson's disease with the dopamine receptor agonist ropinirole, with the addition of levodopa as needed, reduces the risk of dyskinesia compared with levodopa therapy alone, without compromising management of the disease.

The finding is reported in the May 18th issue of The New England Journal of Medicine. In the paper, a multicenter team of researchers led by Dr. Olivier Rascol, of University Hospital in Toulouse, France, point out that whether Parkinson's therapy should begin with levodopa or a dopamine agonist has been a source of controversy among neurologists.

In an attempt to resolve the issue, the researchers conducted a 5-year prospective, double-blind trial of the two approaches in 268 patients with early Parkinson's disease. Of these patients, 179 were randomized to receive ropinirole and 89 to levodopa. Patients in either group whose symptoms persisted after adjusting medication doses could receive supplementary levodopa.

After 5 years of treatment, 47% of the patients taking ropinirole and 51% of those taking levodopa were still enrolled. Supplemental levodopa was prescribed to 51% of all patients in the ropinirole group and 35% of the levodopa group.

During the study, only 20% of patients in the ropinirole group developed dyskinesia, compared with 45% of the levodopa group. The rate of disabling dyskinesia was also significantly lower in patients taking ropinirole than in those taking levodopa, 8% vs. 23%.

In addition, ropinirole and levodopa provided similar control of symptoms. "The mean scores for activities of daily living remained similar in the two groups at each time point during the study...and the changes between base line and completion of the study in the two groups were not significantly different," the authors write.

Despite concerns that dopamine agonists may cause more adverse effects like nausea, hypotension and hallucinations than levodopa, the doses of ropinirole used in the study, which were higher than normally prescribed in the United States, "...were well tolerated, with rates and profiles of adverse events that were similar for the two drugs and typical for any effective dopaminergic agent," the authors state.

"Our study, therefore, demonstrates that Parkinson's disease can be successfully managed for up to five years with ropinirole, with supplemental levodopa given as a second step if necessary," Dr. Rascol and colleagues conclude. "Such treatment significantly lowers the risk of dyskinesia as compared with treatment with levodopa alone."

N Engl J Med 2000;342:1484-1491.

Galantamine Benefits Cognitive, Behavioral, Functional Aspects of Alzheimer's

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WESTPORT, Jul 10 (Reuters Health) - Several domains affected by Alzheimer's disease (AD) are improved or stabilized by the use of the drug galantamine, a novel acetylcholinesterase inhibitor that also potentiates cholinergic nicotinic neurotransmission.

In a placebo-controlled, double-blind study, Dr. Pierre N. Tariot, of the University of Rochester, in New York, and colleagues enrolled 978 patients with mild to moderate AD. Dr. Tariot told Reuters Health, "Our study showed clear-cut differences between drug and placebo in all the domains of interest in AD." These included cognitive function, activities of daily living, and behavioral and emotional changes common to the disease.

In terms of overall clinical response to therapy, 68% of those using galantamine 24 mg/day remained stable or improved after 5 months, compared with 47% of those treated with placebo. Patients treated with galantamine also scored significantly better on the cognitive subscale of the AD Assessment Scale after 5 months, compared with those in the placebo group, whose scores declined.

Similar trends were observed in patients' ADL and scores on the Neuropsychiatric Inventory at 5 months.

Three dosages of galantamine were evaluated: 8, 16, and 24 mg/day. "The fact that there was a very orderly dose-dependent effect is very encouraging," Dr. Tariot told Reuters Health.

While admitting that he probably represents a radical perspective, Dr. Tariot is enthusiastic about galantamine's potential for treating other disorders that target the cholinergic system such as, "to name just a few, dementia due to cerebrovascular disease, Parkinson's disease, dementia with Lewy bodies, delirium, head injury, HIV encephalopathy, even multiple sclerosis."

Neurology 2000;54:2269-2276.

Levodopa-Induced Dyskinesia Partially Reversible

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WESTPORT, May 09 (Reuters Health) - Dyskinesia induced in Parkinson's disease patients by long-term levodopa treatment is partially reversible with subthalamic nucleus stimulation, according to a report in the May issue of the Annals of Neurology.

Dr. Isabelle Arnulf, of Groupe-Hospitalier Pitie-Salpetriere in Paris, France, and colleagues studied levodopa-induced dyskinesias in 12 Parkinson's disease patients before and after treatment with continuous, bilateral, high-frequency stimulation of the subthalamic nucleus. Assessments were undertaken 2 hours after the stimulation was interrupted.

Motor scores on the Unified Parkinson's Disease Rating Scale did not differ before and after surgical implantation of the subthalamic nucleus electrodes, according to the report.

"The severity of dystonia during the 'off' period and levodopa-induced dyskinesias during the 'on' period was reduced by 62%...and 54%...respectively," the authors write, though the types of levodopa-induced dyskinesias did not differ. The improvements did not correlate with subthalamic nucleus stimulation duration, the relative dose reduction in levodopa, or a composite measure incorporating both factors.

Improvement in two patients in whom antiparkinsonian medication was completely withdrawn did not differ from that seen in the overall group of patients, the researchers indicate. This fact strongly suggests that levodopa-induced dyskinesias "are unavoidable in patients with severe degeneration of the nigrostriatal pathway irreversibly worsening with time," they suggest.

"The reduced severity of levodopa-induced dyskinesias in the absence of subthalamic nucleus stimulation demonstrates that the sensitization phenomenon resulting from long-term intermittent levodopa administration is partially reversible," the authors conclude.

Ann Neurol 2000;47:655-658.

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Updated 7/18/2000