***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: OBJECTIVES The objectives of this study were to evaluate the efficacy , safety , and tolerability of quetiapine for treating psychosis in patients with probable/possible Alzheimer disease and assess its impact on other psychopathology and social and daily functioning . METHOD The authors conducted a multicenter , double-blind , placebo-controlled , r and omized trial of flexibly dosed quetiapine and haloperidol . Primary outcomes were change in total Brief Psychiatric Rating Scale ( BPRS ) and Clinical Global Impressions-Severity of Illness ( CGI-S ) scores at week 10 . Secondary outcomes included BPRS factors , Neuropsychiatric Inventory ( NPI ) , Multidimensional Observation Scale for Elderly Subjects ( MOSES ) , and Physical Self-Maintenance Scale ( PSMS ) . RESULTS Two hundred eighty-four participants ( mean age : 83.2 years ) were r and omized ; 63.4 % completed ; and mean Mini-Mental State Examination score was 12.8 . Median of the mean daily dose was 96.9 mg for quetiapine and 1.9 mg for haloperidol . No differential benefit was seen on any psychosis measure . BPRS agitation factor scores improved with quetiapine versus placebo and not quetiapine versus haloperidol .  BPRS anergia scores worsened with haloperidol versus quetiapine but not quetiapine versus placebo . No NPI factors showed change , including the agitation factor . MOSES Withdrawal Subscale and PSMS total scores worsened with haloperidol versus quetiapine .  Somnolence occurred in 25.3 % , 36.2 % , and 4.1 % of the quetiapine , haloperidol , and placebo groups , respectively ; parkinsonism was most prevalent in the haloperidol group ; other safety and tolerability measures differed little among groups . CONCLUSION All treatment groups showed improvement in measures of psychosis without significant differences between them when planned comparisons were performed . Participants treated with quetiapine or haloperidol showed inconsistent evidence of improvement in agitation . Tolerability was better with quetiapine compared with haloperidol Introduction : Psychosis ( delusions and /or hallucinations ) is a well-recognized complication of treatment of Parkinson ’s disease ( PD ) . Quetiapine is a currently favored treatment , but data on its efficacy are equivocal . This trial aim ed to provide further evidence on the efficacy of quetiapine in PD psychosis . Methods : We conducted a 12 week double blind r and omized placebo-controlled trial . Time to dropout due to lack of improvement of psychosis was the primary outcome measure . Other important secondary outcomes were evaluated using st and ard rating scales for PD and psychiatric symptoms . Results : Twenty-four eligible subjects gave consent . The primary outcome , time to dropout , was examined using survival analysis . It was shown that patients in the quetiapine group dropped out earlier than those in the placebo group , but this difference was not significant ( p = 0.68 ) . No significant changes were found for any of the secondary outcome measures in either group . Conclusions : In this study , quetiapine at doses of up to 150 mg/day failed to significantly improve psychosis compared to placebo , however the small sample size does not allow any conclusive interpretation of the results . Quetiapine did not appear to worsen PD motor functioning , but its use was limited by a faster drop out compared with placebo . Significant impediments were difficulty with recruitment and natural fluctuation in symptoms during the trial BACKGROUND To evaluate the antipsychotic efficacy of olanzapine ( OLZ ) in patients with Parkinson 's disease ( PD ) and drug-induced psychosis ( DIP ) and its repercussion on the motor function . METHODS Ten patients ( 5 women and 5 men ) diagnosed of PD and DIP , aged 67 years ( range : 50 - 81 ) , with PD duration of 11.1 years ( range : 6 - 23 ) , treated chronically with levodopa per day  , received a dose of 2.5 or 5.0 mg OLZ daily . Data concerning improvement of psychosis and worsening of motor function was based on Positive And Negative Symptoms Scale ( PANSS ) and Unified Parkinsons Disease Rating Scale ( UPDRS ) motor . RESULTS Psychotic symptoms were improved in all patients . In most of them the improvement was almost total . Seven patients increased levodopa dose on OLZ , but significant worsening of motor function was reported just in one patient . None of the patients had agranulocytosis in the blood monitoring . Two patients presented weight gain . Seven patients improved their cognitive status . CONCLUSIONS We conclude that OLZ at the doses studied may have efficacy for DIP which appears in PD and does not induce worsening of motor function in most of the patients Objective : To compare the efficacy and safety of clozapine in drug induced psychosis in Parkinson ’s disease ( PD ) . Methods : A four week , r and omised , double blind , parallel comparison of clozapine and placebo , followed by a 12 week clozapine open period , plus a one month period after drug discontinuation , in 60 patients with PD . The primary efficacy outcome was the “ clinical global impression scale ” ( CGI ) ; the positive subscore of the “ positive and negative syndrome scale ” ( PANSS ) was used as the secondary efficacy parameter and the “ unified Parkinson ’s disease rating scale ” ( UPDRS ) and the “ mini mental test examination ” ( MMSE ) as safety outcomes . Results : The mean ( SD ) dosage of clozapine was 35.8 ( 12.5–50 ) mg at the end of the double blind period . The mean ( SD ) scores on the CGI improved by 1.8 ( 1.5 ) for the clozapine group compared with 0.6 ( 1.1 ) for the placebo group ( p = 0.001 ) . The mean ( SD ) positive subscore of PANSS improved by 5.6 ( 3.9 ) for the clozapine group ( 0.8 ( 2.8 ) for the placebo group ; p < 0.0001 ) . At the end of the open period , 25 patients had completely recovered from delusions and hallucinations , and 19 experienced a relapse within one month after the clozapine washout period . The UPDRS motor and MMSE mean scores did not change significantly in either group . Somnolence was more frequent with clozapine than with placebo . Conclusions : Clozapine at a mean dose lower than 50 mg/day improves drug induced psychosis in PD without significant worsening of motor function , and the effect wears off once the treatment stops Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more In a double-blind placebo-controlled study , we evaluated the effects of clozapine ( 75 to 250 mg/day , mean 170.8 ) on  dopaminomimetic psychosis and parkinsonian disability .  Clozapine prevented deterioration of psychosis during the increase of dopaminomimetics in the 3 patients who completed the study .  Worsening of parkinsonism occurred in 3 of the 6 patients . In the dosage used , clozapine 's usefulness was limited by its propensity to produce sedation , confusion , and increased parkinsonism BACKGROUND Parkinson 's disease psychosis , which includes hallucinations and delusions , is frequent and debilitating in people with Parkinson 's disease . We aim ed to assess safety and efficacy of pimavanserin , a selective serotonin 5-HT2A inverse agonist , in this population . METHODS In our 6 week , r and omised , double-blind , placebo-controlled study , we enrolled adults ( aged ≥40 years ) with Parkinson 's disease psychosis . Antipsychotic treatments were not permitted during the study , but controlled antiparkinsonian medication or deep brain stimulation was allowed . Eligible participants entered a 2 week non-pharmacological lead-in phase to limit the placebo response , after which they were r and omly allocated ( 1:1 ) to receive pimavanserin 40 mg per day or matched placebo . The primary outcome was antipsychotic benefit as assessed by central , independent raters with the Parkinson 's disease-adapted scale for assessment of positive symptoms ( SAPS-PD ) in all patients who received at least one dose of study drug and had a SAPS assessment at baseline and at least one follow-up . We assessed safety and tolerability in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT01174004 . FINDINGS Between Aug 11 , 2010 , and Aug 29 , 2012 , we r and omly allocated 199 patients to treatment groups . For 90 recipients of placebo and 95 recipients of pimavanserin included in the primary analysis , pimavanserin was associated with a -5·79 decrease in SAPS-PD scores compared with -2·73 for placebo ( difference -3·06 , 95 % CI -4·91 to -1·20 ; p=0·001 ; Cohen 's d 0·50 ) . Ten patients in the pimavanserin group discontinued because of an adverse event ( four due to psychotic disorder or hallucination within 10 days of start of the study drug ) compared with two in the placebo group . Overall , pimavanserin  was well tolerated with no significant safety concerns or worsening of motor function . INTERPRETATION Pimavanserin may benefit patients with Parkinson 's disease psychosis for whom few other treatment options exist . The trial design used in this study to manage placebo response could have applicability to other studies in neuropsychiatric disease . FUNDING ACADIA Pharmaceuticals Objective : To compare olanzapine and clozapine for safety and efficacy measures of psychosis and motor function in patients with PD and chronic hallucinations . Background : Hallucinations occur in approximately one third of patients with PD treated chronically with dopaminergic drugs . Although clozapine is known to be an effective antipsychotic agent that does not significantly exacerbate parkinsonism , its use requires frequent blood count assessment . Olanzapine is another novel antipsychotic that is not associated with blood dyscrasia , and if equally effective could become the preferred drug for treating hallucinations in subjects with PD . Methods : A r and omized , double-blind , parallel comparison of olanzapine and clozapine in patients with PD with chronic hallucinations was conducted . The primary outcome measure was the Scale for the Assessment of Positive Symptoms ( SAPS ) for psychotic symptoms . The Unified Parkinson ’s Disease Rating Scale ( UPDRS ) motor subscale was used as a secondary outcome measure and as a safety monitoring tool . Results : After 15 patients had completed the study , safety stopping rules were invoked because of exacerbated parkinsonism in olanzapine-treated subjects . UPDRS motor impairment scores from baseline to study end significantly increased with olanzapine treatment , and change scores between the olanzapine and clozapine groups significantly differed . The primary clinical domains responsible for the motor decline were gait and bradykinesia . Even with a smaller patient number than originally anticipated , clozapine significantly improved hallucinations and overall behavioral assessment , whereas olanzapine had no effect . Conclusions : At the doses studied , olanzapine aggravates parkinsonism in comparison with clozapine and should not be regularly used in the management of hallucinations in patients with PD Objective : To assess the efficacy and tolerability of quetiapine for agitation or psychosis in patients with dementia and parkinsonism . Methods : Multicenter r and omized , double-blind , placebo-controlled parallel groups clinical trial involving 40 patients with dementia with Lewy bodies ( n = 23 ) , Parkinson disease ( PD ) with dementia ( n = 9 ) , or Alzheimer disease with parkinsonian features ( n = 8) . The main outcome measure for efficacy was change in the Brief Psychiatric Rating Scale ( BPRS ) from baseline to 10 weeks of therapy . For tolerability it was change in the Unified PD Rating Scale ( UPDRS ) motor section over the same time period . The trial was confounded by the need for a design change and incomplete recruitment . Results : No significant differences in the primary or secondary outcome measures of efficacy were observed . An unexpectedly large placebo effect , inadequate dosage ( mean 120 mg/day ) , and inadequate power may have contributed to lack of demonstrable benefit . Quetiapine was generally well-tolerated and did not worsen parkinsonism , but was associated with a trend toward a decline on a measure of daily functioning . Conclusions : Quetiapine was well-tolerated and did not worsen parkinsonism . Although conclusions about efficacy may be limited , the drug in the dosages used did not show demonstrable benefit for treating agitation or psychosis in patients with dementia and parkinsonism . These findings are in keeping with prior studies reporting limited efficacy of various medications for reducing behavioral problems in demented patients Polysomnographic studies of Parkinson 's disease ( PD ) patients with visual hallucinations ( VH ) usually reveal short , fragmented rapid eye movement ( REM ) sleep , with lower sleep efficiency and reduced total REM sleep . Quetiapine has been demonstrated in open-label trials to be effective for the treatment of insomnia and VH in PD . To confirm quetiapine 's efficacy in improving VH , and to determine whether the mechanism was due to its effect on REM sleep architecture , we performed a pilot , 
    Output:
    
Although clozapine had an effective and relatively safe profile , all atypical antipsychotics included in the present study may be unsafe , as they may worsen motor function when compared to placebo