***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 : Parkinson disease ( PD ) is a common neurodegenerative disease affecting up to 1 million individuals in the United States . Depression affects up to 50 % of these patients and is associated with a variety of poor outcomes for patients and their families . Despite this , there are few evidence -based data to guide clinical care . Methods : An NIH-funded , r and omized , controlled trial of paroxetine CR , nortriptyline , and placebo in 52 patients with PD and depression . The primary outcomes were the change in the Hamilton Depression Rating Scale ( HAM-D ) and the percentage of depression responders at 8 weeks . Results : Nortriptyline was superior to placebo for the change in HAM-D ( p < 0.002 ) ; paroxetine CR was not . There was a trend for superiority of nortriptyline over paroxetine CR at 8 weeks ( p < 0.079 ) . Response rates favored nortriptyline ( p = 0.024 ) : nortriptyline 53 % , paroxetine CR 11 % , placebo 24 % . In planned contrasts of response rates , nortriptyline was superior to paroxetine CR ( p = 0.034 ) . Nortriptyline was also superior to placebo in many of the secondary outcomes , including sleep , anxiety , and social functioning , while paroxetine CR was not . Both active drug treatments were well tolerated . Conclusions : Though relatively modest in size , this is the largest placebo-controlled trial done to date in patients with Parkinson disease ( PD ) and depression .  Nortriptyline was efficacious in the treatment of depression and paroxetine CR was not . When compared directly , nortriptyline produced significantly more responders than did paroxetine CR . The trial suggests that depression in patients with PD is responsive to treatment and raises questions about the relative efficacy of dual reuptake inhibitors and selective serotonin reuptake inhibitors . ARR = absolute risk reduction ; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders , 4th edition ; HAM-A = Hamilton Anxiety Scale ; HAM-D = Hamilton Depression Rating Scale ; MMSE = Mini-Mental State Examination ; NNT = number needed to treat ; PD = Parkinson disease ; PDQ = Parkinson ’s Disease Question naire ; PSQI = Pittsburgh Sleep Quality Index ; SCID = Structured Clinical Interview ; SSRI = selective serotonin reuptake inhibitor ; TCA = tricyclic antidepressant ; UPDRS = Unified Parkinson ’s Disease Rating Scale OBJECTIVE To evaluate the efficacy and safety of donepezil , an acetylcholinesterase inhibitor , as a treatment for cognitive impairment and dementia in patients with Parkinson ' s disease ( PD ) . METHODS Using a r and omized , double-blind , placebo-controlled design , nine patients received placebo and seven patients received donepezil ( 2.5 - 10 mg/day ) for a mean ( SD ) duration of 15.2 ( 3.4 ) weeks . The primary efficacy outcomes were derived from a neuropsychological battery that assessed global cognitive status as well as memory , attention , psychomotor speed , and visuospatial and executive functions . Secondary efficacy outcomes were psychiatric symptom and activities of daily living ratings . Primary safety measures were motor signs and assessment s of adverse effects . RESULTS Patients on donepezil showed selective and significant ( p<0.05 ) improvement on the memory subscale of the Dementia Rating Scale . There was also a trend toward improvement on a measure of psychomotor speed and attention . There were no group differences in psychiatric status , motor function , or activities of daily living as measured at baseline or end-point . Adverse effects result ed in premature withdrawal of four patients on donepezil , two for peripheral cholinergic effects and one for increased parkinsonism . Side effects were associated with dosage increases . CONCLUSION Donepezil has a beneficial effect on memory and may improve other cognitive deficits in patients with PD and cognitive impairment . However , variable tolerability in our sample underscores the need for careful monitoring when prescribing donepezil to patients with PD , especially with dosage increases Background : Excessive daytime somnolence ( EDS ) commonly complicates Parkinson ’s disease ( PD ) . The aetiology of EDS is probably multifactorial but is probably exacerbated by dopaminergic medications . Modafinil is a wake-promoting agent approved for use in narcolepsy , but it is often used to treat a variety of somnolent conditions . Method : A double blind , placebo controlled parallel design trial was conducted to assess the efficacy of modafinil ( 200–400 mg/day ) for the treatment of EDS in PD . The primary efficacy measure was the Epworth Sleepiness ( ES ) scale score . Secondary efficacy points included the Unified Parkinson ’s Disease Rating Scale ( UPDRS ) , the Fatigue Severity Scale , the Hamilton Depression Scale , and the multiple sleep latency test ( MSLT ) . Results : Of a total of 40 subjects ( 29 men , mean ( SD ) age 64.8 ( 11.3 ) years ) , r and omised to modafinil or placebo , 37 completed the study . Modafinil failed to significantly improve ES scores compared with placebo ( 2.7 v 1.5 points improvement , respectively , p = 0.28 ) . MSLT failed to improve with modafinil relative to placebo ( −0.16 v −0.70 , respectively , p = 0.14 ) . UPDRS , global impressions , Fatigue Severity Scale , and Hamilton Depression Scale scores were unchanged . Adverse events were minimal . Conclusion : Modafinil failed to significantly improve EDS in PD compared with placebo . The drug did not alter motor symptoms in PD and was well tolerated BACKGROUND Non-motor symptoms of Parkinson 's disease ( PD ) represent major causes of morbidity . RECOVER , a r and omized controlled trial of rotigotine transdermal system , was the first prospect i ve controlled trial to use the Non-Motor Symptoms Scale ( NMSS ) as an exploratory outcome for assessment of treatment effects on non-motor symptoms in PD . Rotigotine improved NMSS total score compared with placebo , and the " Sleep/fatigue " and " Mood/apathy " domains . This post hoc analysis further characterizes the effects of rotigotine on sleep/fatigue and mood/apathy . METHODS Patients with PD and unsatisfactory early-morning motor impairment were r and omized to transdermal patches of rotigotine ( 2 - 16 mg/24 h ) or placebo .  Treatment was titrated to optimal dose over 1 - 8 weeks , maintained for 4 weeks . The NMSS was assessed at baseline and end of treatment . Post hoc analyses are presented for individual items of the " Sleep/fatigue " and " Mood/apathy " domains . The interpretation of p-values is considered exploratory in nature . RESULTS Of 287 patients r and omized ,  NMSS data were available for 267 patients ( 178 rotigotine , 89 placebo ) . Within the " Sleep/fatigue " domain there was a significant difference , in favor of rotigotine , in change from baseline score in 1 of 5 items : " fatigue ( tiredness ) or lack of energy " ( ANCOVA , p < 0.0001 ) . Within the " Mood/apathy " domain , there were significant differences in favor of rotigotine in 4 of 7 items : " lost interest in surroundings " ( p < 0.0001 ) , " lost interest in doing things " ( p < 0.0001 ) , " seems sad or depressed " ( p < 0.01 ) , and " difficulty experiencing pleasure " ( p < 0.05 ) . CONCLUSIONS Rotigotine transdermal system may improve non-motor symptoms such as fatigue , symptoms of depression , anhedonia , and apathy in patients with PD ; further prospect i ve controlled studies are required to confirm this post hoc analysis The serotonergic hypothesis for depression in Parkinson 's disease ( PD ) states that the reduced cerebral serotonergic activity that occurs in PD constitutes a biological risk factor for depression . The aim of our study was to assess the serotonergic hypothesis of depression in PD patients using an experimental approach . In a double-blind , r and omized order , placebo-controlled crossover design , the response on the Profile of Mood States ( POMS ) question naire to acute tryptophan depletion ( ATD ) was studied in 15 PD nondepressed patients and 15 control subjects , without a prior personal or family history of depression . PD patients had lower ( worse ) baseline scores on the sadness , fatigue and vigor subscales of the POMS , in both ATD and the placebo condition , but not on the tension and anger subscales . There was however neither a significe between group effect , nor significe within-group effect due to ATD . We could find no evidence of a specific serotonergic vulnerability of PD patients for depression . Therefore , our results do not support the serotonergic hypothesis for depression in PD BACKGROUND The ADAGIO study investigated whether rasagiline has disease-modifying effects in Parkinson 's disease .  Rasagiline 1 mg per day , but not 2 mg per day , was shown to be efficacious in the primary analysis . Here , we report additional secondary and post-hoc analyses of the ADAGIO study . METHODS ADAGIO was a placebo-controlled , double-blind , multicentre , delayed-start study , in which 1176 patients with untreated early Parkinson 's disease were r and omly assigned to receive rasagiline 1 mg or 2 mg per day for 72 weeks ( early-start groups ) or placebo for 36 weeks followed by rasagiline 1 mg or 2 mg per day for 36 weeks ( delayed-start groups ) . We assessed the need for additional antiparkinsonian therapy and changes in non-motor experiences of daily living and fatigue scales ( prespecified outcomes ) and changes in unified Parkinson 's disease rating scale ( UPDRS ) scores and subscores in placebo and active groups ( post-hoc outcomes ) . The ADAGIO study is registered with Clinical Trials.gov , number NCT00256204 . FINDINGS The need for additional antiparkinsonian therapy was reduced with rasagiline 1 mg ( 25 of 288 [ 9 % ] patients ) and 2 mg ( 26 of 293 [ 9 % ] ) versus placebo ( 108 of 593 [ 18 % ] ; odds ratio for 1 mg rasagiline vs placebo 0·41 , 95 % CI 0·25 - 0·65 , p=0·0002 ; 2 mg rasagiline vs placebo 0·41 , 0·26 - 0·64 , p=0·0001 ) . At week 36 , both doses significantly improved UPDRS motor subscores  compared with placebo ( 1 mg rasagiline mean difference -1·88 [ SE 0·35 ] ; 2 mg rasagiline -2·18 [ 0·35 ] ; both p<0·0001 ) and activities of daily living subscores ( ADL ; 1 mg rasagiline -0·86 [ 0·18 ] ; 2 mg rasagiline -0·88 [ 0·18 ] ; both p<0·0001 ) , and 1 mg rasagiline significantly improved UPDRS mentation subscore ( -0·22 [ 0·08 ] ; p=0·004 ) . At week 72 , the only significant difference between early-start and delayed-start groups was for ADL subscore with the 1 mg dose ( -0·62 [ 0·29 ] ; p=0·035 ) . When assessed for the effect on non-motor symptoms at week 36 , both doses showed benefits on the Parkinson fatigue scale  versus placebo ( 1 mg rasagiline mean difference -0·14 [ SE 0·05 ] , p=0·0032 ; 2 mg rasagiline -0·19 [ 0·05 ] , p<0·0001 ) , and the 1 mg dose showed benefits on the scale for non-motor experiences of daily living compared with placebo ( mean difference -0·33 [ 0·17 ] ; p=0·049 ) . The rate of progression of total UPDRS score for patients in the placebo group was 4·3 points [ SE 0·3 ] over 36 weeks , with extrapolation to about 6 units per year . In the placebo group , patients with the lowest quartile of baseline UPDRS scores ( ≤14 ; n=160 ) progressed more slowly than did those with highest scores ( > 25·5 ; n=145 ; mean difference -3·46 [ SE 0·77 ] ; p<0·0001 ) . INTERPRETATION These findings show that rasagiline delayed the need for symptomatic antiparkinsonian drugs and emphasise the contribution of the UPDRS ADL in the response of the rasagiline 1 mg per day early-start versus delayed-start group . The rate of UPDRS deterioration was less than was anticipated from previous studies and correlated with baseline severity . Underst and ing of the pattern of UPDRS deterioration is essential to assess disease modification . FUNDING Teva Pharmaceutical Industries and H Lundbeck In recent years quality of life instruments have been featured as primary outcomes in many r and omized trials . One of the challenges facing the investigator using such 
    Output:
    
None of the other pharmacological interventions affected subjective fatigue in PD .
Based on the current evidence , no clear recommendations for the treatment of subjective fatigue in PD can be provided .
Rasagiline may be effective in reducing levels of physical fatigue in PD .
No evidence was found for the effectiveness of  levodopa-carbidopa , memantine , caffeine , methylpheni date , modafinil or exercise .