Drugs that improve Parkinson's symptoms may not slow disease progression

Main Category: Parkinson's Disease
Article Date: 25 Aug 2005 - 0:00 PDT

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A class of drugs known as MAO-B inhibitors may be effective in improving motor symptoms in people with early Parkinson's disease and may delay the need for treatment with other drugs, according to a new systematic review of current evidence.

However, contrary to results from other studies, the researchers found that MAO-B (monoamine oxidase B) inhibitors do not appear to slow the disease's progression.

"The benefits of MAO-B inhibitors are small but may be worthwhile in some patients," says Carl Counsell of the University of Aberdeen in Scotland and an author of the review. "I don't think our review supports a policy of putting all newly diagnosed patients on an MAO-B inhibitor, but some patients may wish to try it."

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

Parkinson's disease is a motor system disorder that results from the loss of dopamine-producing brain cells. There is no blood or laboratory test to diagnose Parkinson's and no cure. Current treatment involves the use of drug therapies such as levodopa (L-dopa), which nerve cells use to make dopamine and replenish the brain's dwindling supply, thus improving symptoms.

However, L-dopa becomes less effective over time, and the response to the drug can become erratic, causing fluctuations in motor symptoms and fragmented, jerky motions. Drugs such as MAO-B inhibitors have been under study to delay disease progression and postpone the use of L-dopa.

"We did not find any convincing evidence that MAO-B inhibitors significantly delay disease progression in early [Parkinson's]," the authors write. "Although there is good evidence that MAO-B inhibitors have a levodopa-sparing effect, whether this results in fewer long-term, clinically relevant motor complications is unclear.

"At present we do not feel these drugs can be recommended for routine use in the treatment of early Parkinson's disease," the authors conclude, "but further randomized controlled trials should be carried out to clarify, in particular, their effect on deaths and motor complications."

In the review, researchers looked at 10 clinical trials and 2,422 patients with early Parkinson's who had either not received treatment or had started treatment within the last 12 months. There were three groups of patients followed for an average of almost six years: those given an MAO-B inhibitor (selegiline or lazabemide), those given no treatment and those given a placebo.

The patients on MAO-B inhibitors did have reduced impairment and disability over the short term and few side effects, except one trial that showed increased mortality in patients taking the drugs.

"The existing data do not exclude the possibility that MAO-B inhibitors cause an increase in mortality but, given that only one trial has suggested this, we consider it very unlikely," the authors write.

"MAO-B inhibitors delay the need for levodopa by about six months in patients with early disease," says Counsell. "However, this is almost certainly because they have a mild symptomatic effect rather than fundamentally altering the progression of the disease. The question is whether this short delay is important."

"I suspect that selegiline delays motor fluctuations as it continuously delivers dopamine," says Irene Litvan, M.D. of the University of Louisville School of Medicine. "The unresolved question is if it is truly worthwhile prescribing MAO-B inhibitors. Perhaps rasagiline, another MAO-B inhibitor which is more potent, may have more of a future in treating [Parkinson's] as is offers additional benefits, for instance, as an antioxidant."

Rasagiline is newly licensed MAO-B inhibitor. "I would favor selegiline for further study because this is the most widely used; many would favor rasagiline because newer is often perceived as better," Counsell says.

In the United States, at least 500,000 people are believed to have Parkinson's disease, and about 50,000 new cases are reported annually, affecting about 1 percent to 2 percent of people over the age of 60 years. The chances of developing Parkinson's increase with advancing age. The early-onset form, which accounts for 5 percent to 10 percent of people with Parkinson's, occurs before age 50 (such as seen in actor Michael J. Fox, who was diagnosed in his 30s).

The main symptoms of Parkinson's are subtle and gradually worsen, and include trembling in hands, arms, legs, jaw and face; rigidity, or stiffness of the limbs and trunk; slowness of movement; and postural instability, impaired balance and coordination. As the disease progresses, patients may have difficulty walking, talking or completing other simple tasks. Depression and other emotional changes can also occur.

Macleod AD, et al. Monoamine oxidase B inhibitors for early Parkinson's disease. The Cochrane Database of Systematic Reviews 2005, Issue 3.

The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit cochrane.org for more information.

Carl Counsell
carl.counsell@abdn.ac.uk
Center for the Advancement of Health
http://www.cfah.org