But active ingredient in antidepressant Paxil has no effect on physical symptoms
PORTLAND, Ore. – A well-known drug used to treat hyperactive children boosts the potency of another drug that reduces Parkinson's disease symptoms, an Oregon Health & Science University study has found.
Scientists at the OHSU Parkinson Center of Oregon found that methylphenidate, known commercially as Ritalin, bolsters the effects of levodopa, a drug converted in the brain to dopamine. Methylphenidate inhibits the reabsorption of dopamine into nerve cells, increasing the neurotransmitter's potency.
Parkinson's disease is caused by a deficiency of nerve cells that produce dopamine.
A parallel study by Parkinson center researchers found that paroxetine, a popular antidepressant best known under the brand name Paxil, doesn't augment the effects of levodopa and has little benefit in reducing physical symptoms of Parkinson's disease.
Paroxetine is a selective serotonin reuptake inhibitor, or SSRI, a class of antidepressants that block the reabsorption of another neurotransmitter, serotonin, into nerve cells. Researchers studied it because laboratory evidence has suggested the serotonin transporter, the system through which serotonin is reabsorbed into nerve cells, may take up dopamine as well.
"Both studies looked at the effects of these drugs on Parkinson's disease," said John "Jay" G. Nutt, M.D., professor of neurology, and physiology and pharmacology, OHSU School of Medicine, and director of the Parkinson center. He also is director of the Parkinson's Disease Research, Education, and Clinical Center (PADRECC) at the Portland Veterans Affairs Medical Center. The studies were presented last week at the 56th annual meeting of the American Academy of Neurology in San Francisco.
Ritalin, the drug used in the methylphenidate study, "increases the effects of levodopa," Nutt said, while paroxetine didn't affect Parkinson's disease symptoms. However, paroxetine, when taken without levodopa, did increase the walking speed of Parkinson's patients.
"There was no evidence that (paroxetine) made Parkinson's disease worse, as some clinicians have suggested," Nutt said. "If that occurred, it probably wasn't by negatively impacting dopamine's effects."
In the Ritalin study, 14 Parkinson's disease patients with fluctuating responses to levodopa were examined. All received two-hour levodopa infusions at either minimum or maximum doses for four consecutive days, but some also received oral doses of Ritalin. Participants were then tested for symptoms of Parkinsonism, including tapping and walking speeds; dyskinesia or involuntary movements such as twitching, nodding and jerking; mood, anxiety and fatigue; and sitting blood pressure.
Ritalin amplified the effects of levodopa, particularly for those given minimum doses of levodopa. It increased, from 36 percent to 86 percent, the number of patients responding to levodopa, and it boosted the duration of levodopa response as measured by tapping and walking tests. But the severity of dyskinesia, a side effect of levodopa therapy, did not rise.
In addition, Ritalin decreased another levodopa side effect – hypotension, or low blood pressure – and it enhanced improvements levodopa made in mood and decreased fatigue. Adverse effects, in general, were minimal, and the drug had no effect when given alone to Parkinson's disease patients.
The study's findings do more than show that Ritalin improves patients' responses to levodopa, Nutt said. They confirm the importance of the dopamine transporter, the system through which dopamine is reabsorbed into nerve cells, and shows that the transporter may be a target for other levodopa-boosting drugs.
"It may be that by blocking the dopamine transporter with one drug or another, we can augment the effects of levodopa and get better control of Parkinson's disease," he said.
Pharmaceutical companies already are looking at other drugs that may block the transporter, Nutt added. And the OHSU Parkinson Center will continue to study Ritalin, including whether more doses promotes levodopa response throughout the day.
"The first study is proof of principle – blocking the dopamine transporter," Nutt said. "Now the question is, would Ritalin be the drug to do that? That's not clear."
The paroxetine study was conducted on 14 people with varying severity of Parkinson's disease. Each was given two-hour levodopa infusions; some also received paroxetine for two weeks while the rest were given a placebo. The subjects were then scored for tapping rate, tremor and dyskinesia, as well as walking speed.
Paroxetine, when given with levodopa, didn't affect tapping, dyskinesia or tremor, according to the findings. In fact, six people reported worse balance while on paroxetine.
Nutt's Ritalin study collaborators were Julie H. Carter, R.N., A.N.P., associate professor of neurology, OHSU School of Medicine, and associate director of the Parkinson center; and Gary J. Sexton, Ph.D., associate professor of public health and preventive medicine, OHSU School of Medicine. Paroxetine study collaborators were Kathryn A. Chung, M.D., assistant professor of neurology, OHSU School of Medicine and the Parkinson center, and PADRECC, Portland VA Medical Center.
Source: Eurekalert & othersLast reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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