Pharmacy & Therapeutics - October 2008 - (Page 604)

Medical Management of Parkinson’s Disease Adverse effects. The adverse reactions reported most frequently at the recommended dose of amantadine in 5% to 10% of patients are nausea, dizziness, lightheadedness, and insomnia.54 Less frequently reported effects in 1% to 5% of patients are depression, anxiety and irritability, hallucinations, confusion, anorexia, dry mouth, constipation, ataxia, peripheral edema, orthostatic hypotension, headache, somnolence, nervousness, dream abnormality, agitation, dry nose, diarrhea, mild fatigue and reversible dizziness, lethargy, anticholinergic effects, livedo reticularis, and lower-extremity edema.54 The Shults Study. In one small study, coenzyme Q10 was found to slow the course in PD patients.57 Coenzyme Q10 affects the energy-generating mechanisms in cells. This study suggested that treatment with 1,200 mg/day of coenzyme Q10 resulted in less disability over the fixed period of the study than lower doses of the same compound or a placebo. A larger trial is needed to confirm these findings and to determine the optimal dose of coenzyme Q10 to use. The Storch Study. In this multicenter, randomized, doubleblind, placebo-controlled, stratified, parallel-group, single-dose trial, nanoparticular coenzyme Q10 at a dosage of 300 mg/day was safe and well tolerated. This dose resulted in plasma levels similar to 1,200 mg/day of standard formulations.58 It was concluded that add-on coenzyme Q10 did not produce symptomatic effects in mid-stage PD. Neuroprotective Therapy (Rasagiline, Coenzyme Q10, Levodopa) In addition to controlling the symptoms of PD, it would be advantageous to develop a therapy that modifies the progressive degeneration that governs PD. Current research strategies are based on mechanistic approaches (e.g., energy metabolism, oxidative stress, environmental triggers, and excitotoxicity) and on discoveries related to the genetics of PD.55 The ELLDOPA Study. The Early versus Late Levodopa (ELLDOPA) study, conducted by the Parkinson’s Study Group, was a randomized, double-blind, placebo-controlled, parallelgroup, multisite clinical trial.59 Participants had early PD of no The TEMPO Study. Neuroprotective data were obtained from the Rasagiline Mesylate [TVP-1012] in Early Monothermore than three years’ duration, but they were not otherwise apy for PD Outpatients (TEMPO) delayed-start study and are receiving antiparkinson medications or symptomatic therapy. more encouraging for disease modification.56 The data sugThe investigators enrolled 360 participants, dividing them randomly into four arms to receive low-dose, middle-dose, gested that earlier therapy, in patients without functional and high-dose carbidopa/levodopa, and placebo. The doses of impairment, results in better long-term outcomes.55 the active-treatment groups were titrated during a course of TEMPO was conducted to determine whether rasagiline nine weeks, to 150, 300, and 600 mg/day, respectively. After 40 monotherapy would be useful in early PD. The safety and efweeks, a three-day washout began, followed for two more ficacy of rasagiline, a selective MAO-B inhibitor, were deterweeks without any medications. Patients were followed for 42 mined. The study was a multicenter, 26-week, parallel-group, weeks without medication.59 randomized, double-blind, placebo-controlled trial conducted in movement-disorder clinics. Patients had early PD but did not The primary outcome variables were the change in severneed dopaminergic therapy (n = 404). They were randomly asity, as measured by total UPDRS scores from baseline to week signed to receive rasagiline 1 mg or 2 mg/day or a matching 42. The primary rater saw the participants only twice, at the placebo. A one-week escalation period was followed by a 25baseline evaluation and at week 42, in an effort to maintain week maintenance period. blindness. The treating investigators were also blinded, but The main outcome measure of efficacy was the change in they observed the patients throughout their course. A subset the total UPDRS scores between baseline and 26 weeks of treatof 135 patients underwent before-and-after neuroimaging studment. Rasagiline monotherapy was effective in this 26-week ies, for which the percentage change in the striatal dopamine study. The adjusted effect size for the total UPDRS was –4.20 transporter between baseline and week 40 assessed by cocaine units comparing 1 mg of rasagiline and placebo (95% CI, –5.66 analogue iodine-123-beta-CIT (beta-CIT) uptake measured by to –2.73 units; P < 0.001) and –3.56 units comparing 2 mg and spectroscopy was the primary imaging outcome. There was no placebo (95% CI, –5.04 to –2.08 units; P < 0.001). There were statistical difference in any baseline characteristics, includno meaningful differences in the frequency of adverse events ing race, age, sex, or onset and duration of disease. UPDRS or premature withdrawals among the treatment groups. The scores ranged from 27.3 to 29.4. Of the 361 randomized investigators concluded that rasagiline was ef fective as patients, 311 completed the study.59 monotherapy for patients with early PD. The two dosages in ELLDOPA returned the most significant results in the carthis trial were both effective in relation to placebo.56 bidopa/levodopa 600-mg/day group, according to the primary raters. The placebo group experienced deterioration Table 5 Muscarinic Blocking Agents for the Treatment during the 40-week course and saw little change after of Parkinson’s Disease the washout. The 150-mg/day group improved, but this effect began to be lost by 40 weeks. Greater Medication Available Doses Initial Dosing improvement was seen in the 300- and 600-mg/day Benztropine mesylate 0.5 mg 0.5 mg twice daily groups, and the 600-mg/day dosage maintained its (Cogentin) 1.0 mg effects a little longer than the 300-mg/day dosage. 2.0 mg After two weeks of washout, patients in the 600-mg/ day group were still improved over their baseline Trihexyphenidyl HCl 2 mg 1–2 mg twice daily scores by 1.4 points, but the placebo group worsened (Artane) 5 mg by 7.8 points. These improvements were also true of 604 P&T® • October 2008 • Vol. 33 No. 10

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Pharmacy & Therapeutics - October 2008 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/ New Medical Devices Drug Forecast Medical Management of Parkinson’s Disease Why Is Health Care Regulation So Complex? The Next President’s Prescription for Action on Drugs Trends in Managing Multiple Sclerosis Product Profiler: Sancuso®

Pharmacy & Therapeutics - October 2008

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