Levodopa remains principal treatment for Parkinson's disease

April 1, 2005

Parkinson's Disease is a chronic, progressive neurological disorder that occurs when neurons in the part of the brain that controls movement start to degenerate. This leads to a shortage of the neurotransmitter dopamine, causing characteristic movement problems.

Parkinson's disease affects 1.5 million people in the United States, according to the American Parkinson Disease Assn., and there are about 50,000 new cases reported each year. Many patients need no treatment for several years after initial diagnosis. Symptoms worsen over time, and there is no cure.

LEVODOPA AND CARBIDOPA When symptoms grow severe, doctors usually prescribe levodopa combined with carbidopa.

Both immediate-release and controlled-release formulations of levodopa/carbidopa are available generically. "Controlled-release formulations of levodopa/carbidopa generally are more erratic in their absorption," says Mark Abramowicz, MD, editor of The Medical Letter on Drugs and Therapeutics, a non-profit newsletter that critically appraises drugs. "Some clinicians have the impression that Sinemet CR may be less erratic, but objective data are lacking."

Dopamine agonists, which activate dopamine receptors, have less anti-Parkinson's effect than levodopa, but they are also less likely to cause uncontrollable movements as a side-effect. They include Mirapex (pramipexole) and ReQuip (ropinirole). "New drugs for Parkinson's, such as the dopamine agonists, have come out in recent years. They are considerably more expensive than the older ones, but also have advantages over the older ones," says Mark N. Brueckl, RPh, MBA, pharmacy affairs manager for the Academy of Managed Care Pharmacy. "In general, MCOs are covering the newer drugs, but some are implementing step therapy programs to ensure that older, less-expensive medications are tried first."

"The dopamine agonists are most commonly used as an adjunct to levodopa in advanced disease," Dr. Abramowicz says. "They are also effective in early, mild disease, but in comparative studies, levodopa remained more effective at all time points. Many patients on agonists require the addition of levodopa over time."

Two older, ergot-derived dopamine agonists are still on the market in the United States: Parlodel (bromocriptine), and Permax (pergolide).

However, Dr. Abramowicz notes, "among the dopamine agonists, the newer non-ergot ropinirole and pramipexole should cause fewer adverse effects than the ergots, and they cost less,"

A third class of drugs, the COMT inhibitors, inhibit a gastrointestinal enzyme that metabolizes levodopa, so they prolong the half-life of levodopa without affecting peak concentrations. The COMT inhibitor Comtan (entacapone) is available in various fixed-dose combinations with carbidopa/levodopa.

Another COMT inhibitor, Tasmar (tolcapone), has caused fatal hepatotoxicity and has been taken off the market in Canada and Europe, but is still available in the United States.

Parkinson's is a progressive disease. "Levodopa is really the most effective medication, but eventually it appears to stop working," Dr. Abramowicz says. "The disease progresses. The consensus of opinion now is, it's not that you only have a certain number of years of effectiveness for levodopa. The reality is that after you've been using it for a few years, the disease has progressed."

In addition, there is some risk of levodopa-induced psychosis. Clozaril (clozapine) is an anti-psychotic drug that does not cause drug-induced Parkinsonism and is particularly useful in controlling psychosis associated with levodopa. It is effective at much lower doses than those usually needed to treat schizophrenia.