There are many new drugs now available for the treatment of idiopathic Parkinson’s disease (PD). Careful thought has to be given to the various drugs, their use, and the order in which they are started and added. The guiding principle is evidence-based: does the drug reduce rigidity, tremor, and akinesia, and does it improve activities of daily living and quality of life? Evidence-based data are obtained through double-blind placebo controlled clinical trials. There must be awareness whether the drug does or does not reduce “off” time and increase “on” time, compared to placebo.

Two new drugs have recently been released in the United States. They are Azilect (rasigiline) and Zelapar (selegine HCl).

Azilect is a new second-generation MAO-B inhibitor. Its metabolite is Azilect-aminoiodan, which is not an amphetamine. The drug is given once a day in tablets of 0.5 and 1.0 mg. In tissue-cultures study and in animal models, it has shown to be neuroprotective.

There have been three large clinical trials with this drug. The first trial was TEMPO, a monotherapy trial for newly diagnosed PD patients. Azilect was given over six months. It improved the United PD Rating Scale (UP-DRS) scores by four points over placebo, with few adverse side effects. At six months, the placebo group was given Azilect (medication was switched from placebo to Azilect) and compared to those patients initially on Azilect. The earlier-treated group always remained better than the placebo group. This could possibly indicate disease modification. At two years, 46 percent of patients who were in the study remained adequately controlled on Azilect. After six years, the early Azilect started group had less progression as compared to the delayed start group.

A second study, called PRESTO, was an adjunctive therapy trial. All patients were optimized carbidopa/levodopa treated patients. Many were on dopamine agonists. Placebo was compared to 0.5 mg and 1 mg of active medication. The 0.5 mg patients had a half hour less of “off” time and the 1 mg group had one hour less of “off” time.

LARGO, the third trial, showed that entacapone and Azilect were similar in reducing “off” time, which was 0.8 hours less “off” time in optimized carbidopa/levodopa treated patients. Freezing of the gait was also improved.

There have now been well over a thousand patients who have been on Azilect for up to seven years. I have about 20 patients who have been on Azilect for more that six months, and they appear to be doing quite well.

Significant reduction of “off” time for patients on carbidopa/levodopa is seen using

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Azilect and many of these patients have been on dopamine agonists.

Adverse effects compared to placebo were abnormal dreams, and several other minor side effects. There will probably be a tyramine warning (i.e. cheeses, red wines, etc.) when using this drug. There may be concerns with the use of Selective Serotonin Uptake Inhibitors (SSRI) and antidepressants.

Zelapar (selegiline HCl), a MOA-B inhibitor, is an orally-disintegrating tablet that has been compared to placebo in clinical trials. It is given once a day and has fewer amphetamine metabolites than oral selegiline. Selegiline previously (in the DATATOP study) has been shown to delay L-dopa therapy for nine months and to give some symptomatic benefit. Zelapar has been shown to reduce “off” time by 1.6 hours compared to placebo.

There is an increase in dyskinesia-free “on” time by 1.4 hours over placebo. Titration of Zelapar from 1.25 mg to 2.5 mg occurs in six weeks. Most adverse effects occur in the first six weeks and they may include dizziness, dyspepsia, hallucinations, headaches, dyskinesias and nausea. Eighty per cent of patients did not reduce their dose of L-dopa, but 20% were able to reduce the dose by 50 to 60 mg. There will probably not be a tyramine warning. There may be concerns with the use of SSRIs and antidepressants.

Parkinson’s patients with or without medication may have compulsive and/or impulsive reward seeking behavior, such as overeating, excessive spending, shopping, computer use, and gambling.

Exelon, an acetylcholine esterase inhibitor, has now been shown to improve dementia in PD patients and it has an FDA approval for its treatment. It improves cognition, activities of daily living, and quality of life, and may improve some aspects of behavior and neuropsychiatric symptoms. The caregivers’ impressions supported the clinical improvements suggested by the clinical trials.

The above article was adapted from the one originally published in the November-December 2006 issue of Parkinson Post, the newsletter of the Parkinson’s Disease Association of San Diego.

This article was copied with permission of the American Parkinson Disease Association from their Winter 2007 Newsletter issue.