June 15th, 2015

Levodopa Better First Parkinson’s Drug than MAO Inhibitors or Dopamine Agonists

Levodopa Better First Parkinson's Drug than MAO Inhibitors or Dopamine Agonists

AS I SEE IT:  For years I have preached that Dopamine Agonists (apomorphine>Apokyn<, pramipexole>Mirapex<, ropinirole>Requip<, rotigotine>Neupro<  ) are truly contraindicated in older adults.  Used to treat Parkinson's Disease and Restless Leg Syndrome in almost every case the psychotic symptoms are awful and those that cognitively alert complain and those that are not as cognitively alert end up with additional psychotic diagnosis and additional treatments.  As this article addresses,  the Doctors emphasize that this is general knowledge in the medical community.  Well it surely isn't,  as a matter of fact, since I started keeping records on this serious problem, 100% of the patients I see on Dopamine Agonists are exhibiting serious psychotic problems and drug has to be removed.  

June 25, 2014

NEW YORK - Patients with newly diagnosed Parkinson's disease do better on patient-rated mobility scores if they receive levodopa instead of a levodopa-sparing therapy, new research suggests.

The benefits are very small but persistent, and of the two levodopa-sparing therapies, monoamine oxidase type B inhibitors (MAOBI) were at least as effective as dopamine agonists, the authors reported online June 11 in The Lancet.

"Levodopa has always been referred to as the 'gold standard' treatment for Parkinson's disease. So the trial results are no surprise. Whereas before it was conjecture, we have proved the point," said study co-author Dr. Carl E. Clarke of the University of Birmingham, UK, in an email to Reuters Health.

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Should the findings change clinical practice? "Yes," Dr. Clarke said. "The majority of patients should be initiated on levodopa therapy."

"We have always been uncertain about the relative merits of MAOBIs and dopamine agonists versus levodopa in early Parkinson's disease," said Dr. Clarke. "Does delaying the onset of motor complications, such as involuntary movements, with levodopa-sparing therapy outweigh the benefits of levodopa in treating the basic physical problems in Parkinson's disease?"

"We needed a large-scale long-term trial with patient-rated quality of life outcome measures to decide which is best. The PD MED trial shows that patients tell us that levodopa provides small benefits over and above the dopamine agonists and MAOBIs in their quality of life," he said.

In an open-label trial conducted over almost nine years, Dr. Clarke and colleagues randomized 1,620 patients newly diagnosed with Parkinson's disease to receive either a dopamine agonist, an MAOBI, or levodopa. Patients and investigators were not masked to group assignment.

The researchers - in 91 medical centers in the UK, Czech Republic and Russia - looked for the mobility dimension on the 39-item patient-rated Parkinson's disease questionnaire (PDQ-39) quality-of-life scale. Scores can range from 0 to 100, with six points defined as the minimally important difference).

With a three-year median follow up, PDQ-39 mobility scores averaged 1.8 points (p=0.005) better in patients taking levodopa than in those taking levodopa-sparing therapy. PDQ-39 mobility scores were 1.4 points (p=0.05) better in patients taking MAOBI than in those taking dopamine agonists.

Rates of dementia, admissions to institutions, and death were not significantly different.

Overall, 179 (28%) of the 632 patients who received dopamine agonists and 104 (23%) of the 460 patients who received MAOBI discontinued treatment due to side effects, compared with 11 (2%) of the 528 patients who received levodopa (p<0.0001).

In an editorial, Drs. Anthony E. Lang and Connie Marras of the University of Toronto in Ontario, Canada, wrote that perhaps most importantly, "the results of this study will help to persuade physicians and reassure patients that the fears that have served as the groundwork in establishing levodopa phobia-that often results in patients experiencing unnecessary and easily managed disability and reduction in quality of life in the early years of their disease-are unfounded."

Dr. Stewart A. Factor, professor of neurology at Emory University in Atlanta, Georgia, said in an email, "It is well known that levodopa is the most effective symptomatic therapy for motor features of Parkinson's disease with fewer psychiatric side effects than dopamine agonists.

"The difference between the levodopa and levodopa-sparing groups was not as large as I would have expected, but this could be due to levodopa equivalents and the large percent of patients in the levodopa sparing groups dropping their initial treatment," said Dr. Factor, who was not involved in the study.

As to whether these findings will change clinical practice, he said, "It won't for us. Because of levodopa's superior impact and better side effect profile, we tend to use it first and other drugs as adjunctive therapies.

Agreeing with Drs. Lang and Marris, Dr. Factor added, "We are faced with quite a lot of levodopa phobia in our patients. Marketing strategies for levodopa-sparing drugs have frightened patients, who insist on doing without the most effective drug for their ailment. Adding to their fear, many patients pursue alternative medications from the Internet and organizations that provide alternative therapies, for which there are no data. This a terrible waste of time and money."

"It is up to us to provide the appropriate treatment for our Parkinson's disease patients," he continued. "Levodopa phobia is unfounded and prevents use of our most effective medication. Once on levodopa, patients usually recognize that the benefit outweighs the risk. Dyskinesia is the primary reason for this phobia and most patients would rather have some dyskinesia than have worse parkinsonian features: tremor slowness and stiffness."

SOURCE: http://bit.ly/1jLooN3

Lancet 2014.