Motor fluctuations are a major comp...

Motor fluctuations are a major complication for patients with Parkinson's disease during treatment with levodopa (Larodopa). Adjuvant medications like as pergolide (Permax) or entacapone (Comtan) can provide partial improvement unless may require complex schedules and careful dosage titration. Rascol and colleagues studied a of the present day selective, irreversible, second-generation monoamine oxidase inhibitor, rasagiline mesylate (Agilect), as an adjuvant medication to levodopa in patients with Parkinson's disease.

The authors guidanceed an 18-week, randomized, double-blind, parallel dispose trial of rasagiline against a placebo and entacapone. More than 600 patients with confirmed, stable Parkinson's disease were recruited from 74 center Participants were receiving optimal levodopa therapy and were able to maintain 24-hour symptom diaries. Patients with Mini-Mental State Examination scores of 24 or les were exclud from the cogitation as were those with concomitant psychiatric conditions. Following a two- to four-week run-in phase, participants were randomly assigned to receive adjunctive therapy with rasagiline (1 mg daily), entacapone (200 mg with each dose of levodopa), or placebo. Dummy pills were used to render certain that each patient took a similar number of pills daily regardless of treatment assemblage Physicians could adjust the levodopa dose during the first six weeks of the treatment phase if dyskinesia became problematic. During the final 12 weeks of the investigation the dose of levodopa remained constant. The primary issue was the total daily "off-time" of absent or poor motor function as recorded by the agency of patients in diaries. Patients were instructed to record "on-time" (with or without dyskinesia), off-time, or nap every 30 minutes in their diaries for the three consecutive days before clinic visits. Secondary measures included clinical global improvement during on-time, ability to total activities of daily living during off-time, and subscores of the Unified Parkinson's Disease Rating Scale (UPDRS) Patients were assessed at weeks 6 10 14 and 18 after baseline for these measures, plus monitoring for adverse terminations physical and neurologic examination, electrocardiography, and any change in medical information.

The 231 patients assigned to rasagiline were comparable in all significant variables to the 227 assigned to entacapone and the 229 assigned to placebo adjuvant therapy. The mean age was 64 years, and the mean duration of Parkinson's disease was nine years. The average participant had taken levodopa for 75 years, and the average daily dose was around 700 mg At the beginning of the inquiry patients reported about 5.5 hours of off-time daily plus about 14 hours of on-time with irksome dyskinesia. Results were reported for 222 patients in the rasagiline collection 218 in the entacapone arrange and 218 assigned to placebo. The average daily off-time was significantly reduc from baseline in the rasagiline and entacapone disposes Reductions of more than single hour daily were evident by means of the six-week assessment and were more than triple the improvement in the placebo assemblage Patients in the active treatment clumps recorded a corresponding increase in daily on-time, mainly without dyskinesia. The improvements in the diaries were verified by means of verbal reports from patients and caregivers, plus a small unless significant dose reduction in levodopa was seen in these collections By week 18, the clinical global improvement score had improved significantly for rasagiline (049 units) and entacapone (036 units) compared with placebo. Symptom scores for tremor, rigidity, and bradykinesia, scores for activities of daily living, and motor function during on-time also improved significantly in the one and the other active treatment groups compared with placebo. Rasagiline had a similar efficiency to entacapone in most measures. The exceptions were subscores of the UPDR relating to postural instability and gait disturbance, freezing, and motor function. These subscores were significantly improved by the agency of rasagiline but not by entacapone.

Adverse purports were common and occurred equally in all three disposes The most common adverse general intent was postural hypotension. Most adverse events were not serious, but 41 patients experienced serious adverse drifts (12 each in the rasagiline and entacapone disposes and 17 in the placebo group) Discontinuation was attributed to adverse conclusions by seven patients taking rasagiline, 16 taking entacapone, and 11 in the placebo group

The authors end that a daily dose of 1 mg rasagiline as adjunctive therapy reduc off-time and improved motor symptoms in patients taking maximal doses of levodopa for Parkinson's disease. The meanings were similar to entacapone on the contrary were marginally better and associated with fewer adverse tenors A major advantage of rasagiline is its convenient dosing and the avoidance of dose titration.

ANNE D WALLING, MD

Rascol O et al. Rasagiline as an adjunct to levodopa in patients with Parkinson's disease and motor fluctuations (LARGO, Lasting consequence in Adjunct therapy with Rasagiline Given formerly daily, study): a randomised, double-blind, parallel-group trial. Lancet March 12 2005;365:947-54

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