***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND AND PURPOSE Safinamide is an α-aminoamide with both dopaminergic and non-dopaminergic mechanisms of action in Phase III clinical development as a once-daily add-on to dopamine agonist ( DA ) therapy for early Parkinson 's disease ( PD ) . METHODS Study 017 was a 12-month , r and omized , double-blind , placebo-controlled pre-planned extension study to the previously reported Study 015 . Patients received safinamide 100 or 200 mg/day or placebo added to a single DA in early PD . The primary efficacy endpoint was the time from baseline ( Study 015 r and omization ) to ' intervention ' , defined as increase in DA dose ; addition of another DA , levodopa or other PD treatment ; or discontinuation due to lack of efficacy .  Safinamide groups were pooled for the primary efficacy endpoint analysis ; post hoc analyses were performed on each separate dose group . RESULTS Of the 269 patients r and omized in Study 015 , 227 ( 84 % ) enrolled in Study 017 and 187/227 ( 82 % ) patients completed the extension study .  Median time to intervention was 559 and 466 days in the pooled safinamide and placebo groups , respectively ( log-rank test ; P = 0.3342 ) . In post hoc analyses , patients receiving safinamide 100 mg/day experienced a significantly lower rate of intervention compared with placebo ( 25 % vs. 51 % , respectively ) and a delay in median time to intervention of 9 days ( P < 0.05 ; 240- to 540-day analysis ) . CONCLUSIONS The pooled data from the safinamide groups failed to reach statistical significance for the primary endpoint of median time from baseline to additional drug intervention . Post hoc analyses indicate that safinamide 100 mg/day may be effective as add-on treatment to DA in PD CONTEXT Monotherapy with rasagiline mesylate may be useful in early Parkinson disease ( PD ) . OBJECTIVE To evaluate the safety and efficacy of the selective monoamine oxidase type B inhibitor rasagiline . DESIGN Multicenter , 26-week , parallel-group , r and omized , double-blind , placebo-controlled clinical trial . SETTING Academically based movement disorders clinics . PATIENTS Patients with early PD not requiring dopaminergic therapy ( n = 404 ) . INTERVENTION Research participants were r and omized 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 Scal 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 ; P<.001 ) and -3.56 units comparing a 2-mg dosage and placebo ( 95 % confidence interval , -5.04 to -2.08 units ; P<.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 Background and purpose Depressed mood is a common psychiatric problem associated with Parkinson ’s disease ( PD ) , and studies have suggested a benefit of rasagiline treatment . Methods ACCORDO ( see the 1 ) was a 12-week , double-blind , placebo-controlled trial to evaluate the effects of rasagiline 1 mg/day on depressive symptoms and cognition in non-demented PD patients with depressive symptoms . The primary efficacy variable was the change from baseline to week 12 in depressive symptoms measured by the Beck Depression Inventory ( BDI-IA ) total score . Secondary outcomes included change from baseline to week 12 in cognitive function as assessed by a comprehensive neuropsychological battery ; Parkinson ’s disease quality of life question naire ( PDQ-39 ) scores ; Apathy Scale scores ; and Unified Parkinson ’s Disease Rating Scale ( UPDRS ) subscores . Results One hundred and twenty-three patients were r and omized . At week 12 there was no significant difference between groups for the reduction in total BDI-IA score ( primary efficacy variable ) . However , analysis at week 4 did show a significant difference in favour of rasagiline ( marginal means difference ± SE : rasagiline −5.46 ± 0.73 vs. placebo −3.22 ± 0.67 ; P = 0.026 ) . There were no significant differences between groups on any cognitive test . Rasagiline significantly improved UPDRS Parts I ( P = 0.03 ) and II ( P = 0.003 ) scores versus placebo at week 12 . Post hoc analyses showed the statistical superiority of rasagiline versus placebo in the UPDRS Part I depression item ( P = 0.04 ) and PDQ-39 mobility ( P = 0.007 ) and cognition domains ( P = 0.026 ) . Conclusions Treatment with rasagiline did not have significant effects versus placebo on depressive symptoms or cognition in PD patients with moderate depressive symptoms . Although limited by lack of correction for multiple comparisons , post hoc analyses signalled some improvement in patient-rated cognitive and depression outcomes A median safinamide ( SAF ) dose of 70 mg/day ( range 40 to 90 mg/day ) increased the percentage of parkinsonian patients improving their motor scores by ≥30 % from baseline ( responders ) after 3 months from 21.4 % ( placebo ) to 37.5 % ( p < 0.05 , calculated by logistic regression analysis ) . In a subgroup of 101 patients under stable treatment with a single dopamine agonist , addition of SAF magnified the response ( 47.1 % responders , mean 4.7-point motor score decrease ; p ≥ 0.05 ) . These results suggest that doses of SAF exerting ion channel block and glutamate release inhibition add to its symptomatic effect and warrant exploration of higher doses 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 , r and omized , 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 ± SD age was 62.6 ± 9.7 , and duration of PD was 2.1 ± 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 ± SE , -2.4 ± 0.95 ; 95 % confidence interval [ CI ] , -4.3 , -0.5 ; P = 0.012 ) . Mean improvement ( LS mean ± SE ) was -3.6 ± 0.68 in the rasagiline group and -1.2 ± 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 In a 6-month double-blind , placebo-controlled study of Parkinson 's disease patients with motor fluctuations , safinamide 50 and 100 mg/d significantly increased ON-time without increasing dyskinesia . Further long-term safinamide use in these patients was evaluated over an additional 18 months . Patients continued on their r and omized placebo , 50 , or 100 mg/d safinamide . The primary endpoint was change in Dyskinesia Rating Scale total score during ON-time over 24 months . Other efficacy endpoints included change in ON-time without troublesome dyskinesia , changes in individual diary categories , depressive symptoms , and quality of life measures . Change in Dyskinesia Rating Scale was not significantly different in safinamide versus placebo groups , despite decreased mean total Dyskinesia Rating Scale with safinamide compared with an almost unchanged score in placebo . Ad hoc subgroup analysis of moderate to severe dyskinetic patients at baseline ( 36 % of patients ) showed a decrease with safinamide 100 mg/d compared with placebo ( P = 0.0317 ) . Improvements in motor function , activities of daily living , depressive symptoms , clinical status , and quality of life at 6 months remained significant at 24 months . Adverse events and discontinuation rates were similar with safinamide and placebo . This 2-year , controlled study of add-on safinamide in mid-to-late Parkinson 's disease with motor fluctuations , although not demonstrating an overall difference in dyskinesias between patients and controls , showed improvement in dyskinesia in patients at least moderately dyskinetic at baseline . The study additionally demonstrated significant clinical benefits in ON-time ( without troublesome dyskinesia ) , OFF-time , activities of daily living , motor symptoms , quality of life , and symptoms of depression To confirm the clinical utility of selegiline ( L-deprenyl ) , a selective inhibitor of monoamine oxidase B , as an anti-Parkinson 's disease ( PD ) agent , the first Japanese multi-center , double-blind comparative study of this drug was conducted . The subjects were patients who had responded poorly or suffered with other problems related to L-dopa treatment . A total of 112 patients in two groups , one given selegiline at a dose of 7.5 mg/day ( Group D , n = 60 ) and another given a placebo ( Group P , n = 52 ) , were compared over an 8-week treatment period . The percentage patients showing " moderate improvement " or better was 34.5 % in Group D , while that in Group P was 11.5 % ( P < 0.01 ) . In the assessment of overall safety , 66.7 % in Group D showed no adverse reactions , which was not significantly different from the result of 78.9 % for Group Rasagiline ( N-propargyl-1(R)-aminoindan ) mesylate is a potent , selective , and irreversible monoamine oxidase-B inhibitor . This study was design ed 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 , r and omized , placebo-controlled , 10-week study . Fifty-six PD patients were r and omly 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 ( + /-SE ) changes from baseline in total Unified Parkinson 's Disease Rating Scale ( UPDRS ) score were -1.8 ( + /-1.3 ) , -3.6 ( + /-1.7 ) , -3.6 ( + /-1.2 ) , and -0.5 ( + /-0.8 ) 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 < 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 Levodopa is effective for the motor symptoms of Parkinson 's disease ( PD ) , but is associated with motor fluctuations and dy 
    Output:
    
When ranking the MAO-B inhibitors given in combination with levodopa , selegiline was the most effective and rasagiline was the second best .
All of the included MAO-B inhibitors were effective compared to placebo when given as monotherapy .
Combination therapy with MAO-B inhibitors and levodopa showed that all three MAO-B inhibitors were effective compared to placebo , but selegiline was the most effective drug