Rasagiline and Rapid Symptomatic Motor Effect in Parkinson’s Disease: Review of Literature (original) (raw)
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A Controlled Trial of Rasagiline in Early Parkinson Disease
Archives of Neurology, 2002
Patients: Patients with early PD not requiring dopaminergic therapy (n = 404). Intervention: Research participants were randomized to rasagiline mesylate at dosages of 1 mg or 2 mg per day or matching placebo. A 1-week escalation period was followed by a 25-week maintenance period. Main Outcome Measure: The primary prespecified measure of efficacy was the change in the total Unified Parkinson's Disease Rating Scale score between baseline and 26 weeks of treatment, comparing each active treatment group with the placebo group. Results: Monotherapy with rasagiline was effective in this 26-week study. The adjusted effect size for the total Unified Parkinson's Disease Rating Scale was −4.20 units comparing 1 mg of rasagiline and placebo (95% confidence interval, −5.66 to −2.73 units; PϽ.001) and −3.56 units comparing a 2-mg dosage and placebo (95% confidence interval, −5.04 to −2.08 units; P Ͻ.001). There were no meaningful differences in the frequency of adverse events or premature withdrawals among the treatment groups. Conclusions: Rasagiline is effective as monotherapy for patients with early PD. The 2 dosages in this trial were both effective relative to placebo. Further study is warranted to evaluate the longer-term effects of rasagiline in PD.
European Journal of Neurology, 2010
Rasagiline (Azilect 1) is a highly selective irreversible second generation MAO-B inhibitor indicated for the treatment of idiopathic Parkinson's disease (PD) as monotherapy or as adjunct therapy (with levodopa). The 6-month observational study included 871 patients to investigate the efficacy and tolerability of rasagiline in clinical daily practice focussing on non-motor symptoms and quality of life. Two thirds of the patients received 1 mg rasagiline daily as add-on to their regular PD-medication, the rest as monotherapy. Efficacy criteria were: (1) CURS, (2) PS-23 scale on Parkinson non-motor symptom strength, (3) UPDRS, part IV B, (4) duration of OFF-periods, (5) QoL by PDQ-8, (6) WHO-5 Well-being Index and (7) change of global clinical impression (CGI-I). Significant improvements have been observed in total severity of PD: PS-23 total score declined from 46.4 to 42.2. Health and general well-being measured by PDQ-8 improved significantly from baseline 16.3 to 14.3. Emotional well-being according to WHO-5 improved significantly from 14.4 to 16.4. Positive effects of rasagiline on motor symptoms have been observed: CURS total score improved significantly from 14.8 to 11.4. The proportion of patients without any OFF period increased from 47.1% to 59.1%. Patients reported that OFF periods decreased significantly, most pronounced the morning OFF. Rasagiline has shown to be effective either in monotherapy or in combination with L-Dopa, dopamine agonists or both. AEs were reported by 6.5% of the patients. The treatment with rasagiline in patients with PD resulted in improvements of motor and non-motor symptoms and led to an improved quality of life. 2015 Elsevier GmbH. All rights reserved.
Movement Disorders, 2004
Rasagiline (N-propargyl-1(R)-aminoindan) mesylate is a potent, selective, and irreversible monoamine oxidase-B inhibitor. This study was designed to evaluate the safety, tolerability, and preliminary efficacy of rasagiline monotherapy in early Parkinson's disease (PD) patients not receiving levodopa. The study was performed as a multicenter, parallel-group, double-blind, randomized, placebo-controlled, 10-week study. Fifty-six PD patients were randomly assigned to rasagiline mesylate 1, 2, or 4 mg once daily, or placebo. A 3-week dose-escalation period was followed by a 7-week maintenance phase. At week 10, the mean (ϮSE) changes from baseline in total Unified Parkinson's Disease Rating Scale (UPDRS) score were Ϫ1.8 (Ϯ1.3), Ϫ3.6 (Ϯ1.7), Ϫ3.6 (Ϯ1.2), and Ϫ0.5 (Ϯ0.8) in the rasagiline 1, 2, and 4 mg/day and placebo groups, respectively. Analysis of responders showed that 28% of patients (12 of 43) receiving rasagiline had an improvement in total UPDRS score of greater than 30%, compared with none of the patients receiving placebo (P Ͻ 0.05, Fisher's exact test). The frequency and types of adverse events reported by rasagiline-treated and placebo-treated patients were similar. These results suggest that rasagiline monotherapy is well tolerated and efficacious in early PD.
Movement Disorders, 2008
A neuroprotective therapy is the single most important unmet medical need in Parkinson's disease. Several promising agents in the laboratory have been tested in the clinic, but none has been established in clinical trials to have a disease modifying effect despite positive results because of potential confounding symptomatic or pharmacologic effects. The delayed start design was developed to try to avoid a symptomatic confound when testing a putative neuroprotective therapy. In this study design, patients are randomly assigned to study drug or placebo in the first phase of the study, and both groups receive the active drug in the second phase. If benefits seen at the end of phase I persist through the end of phase II, they cannot be readily explained by a symptomatic effect (as patients in both groups are receiving the same medication) and benefits in the early start group must relate to the early initiation of the treatment. Although the precise mechanism responsible for such an effect can be debated, positive results in a delayed start study indicate that patients who receive early treatment have a better outcome than those where
Randomized, Controlled Trial of Rasagiline as an Add-on to Dopamine Agonists in Parkinson's Disease
A B S T R AC T : Dopamine agonists (DA) are often used as first-line monotherapy for the symptomatic control of Parkinson's disease (PD). However, DA monotherapy typically becomes inadequate within a few years, at which time the DA dosage must be increased or other antiparkinsonian medications added. Adding a monoamine oxidase-B (MAO-B) inhibitor to DA monotherapy might improve symptomatic control while maintaining good safety and tolerability. We conducted an 18-week, randomized, double-blind, placebo-controlled trial of rasagiline 1 mg/d as an add-on to DA therapy (ropinirole 6 mg/d or pramipexole 1.0 mg/d) in early PD patients whose conditions were not adequately controlled on their current treatment regimen. The primary efficacy variable was the change in total Unified Parkinson Disease Rating Scale (UPDRS) score (sum of parts I, II, and III) from baseline to week 18, comparing rasagiline and placebo groups. The modified intent-to-treat (ITT) population included 321 subjects whose mean 6 SD age was 62.6 6 9.7, and duration of PD was 2.1 6 2.1 years. Results demonstrated a significantly greater improvement in total UPDRS scores from baseline to week 18 in the rasagiline group compared with the placebo group (least squares [LS] mean difference 6 SE, 22.4 6 0.95; 95% confidence interval [CI], 24.3, 20.5; P 5 0.012). Mean improvement (LS mean 6 SE) was 23.6 6 0.68 in the rasagiline group and 21.2 6 0.68 in the placebo group. Rasagiline was well tolerated, and the most common adverse events (AEs; rasagiline vs. placebo) were dizziness (7.4% vs. 6.1%), somnolence (6.8% vs. 6.7%), and headache (6.2% vs. 4.3%). Rasagiline 1 mg/d provided statistically significant improvement when added to dopamine agonist therapy and was well tolerated.
2015
IMPORTANCE Depression, cognitive impairment, and other nonmotor symptoms (NMSs) are common early in Parkinson disease (PD) and may be in part due to disease-related dopamine deficiency. Many patients with PD are treated with antidepressants for NMSs, and the effect of the combination of PD medications that enhance dopamine neurotransmission and antidepressants on NMSs has not been studied. We report the effects of the addition of a monoamine oxidase B inhibitor, rasagiline, to antidepressant treatment in PD. OBJECTIVE To evaluate the effect of rasagiline on depression, cognition, and other PD NMSs in patients taking an antidepressant in the Attenuation of Disease Progression With Azilect Given Once Daily (ADAGIO) study. DESIGN, SETTING, AND PARTICIPANTS The ADAGIO study was a double-blind, placebo-controlled, delayed-start trial of rasagiline in de novo PD. In this exploratory post hoc analysis, we analyzed patients taking an antidepressant during the 36-week phase 1 period, in whic...