***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: Abstract Haloperidol treatment has been shown to produce oxidative stress in patients with acute psychosis . Oxidative stress has also been implicated in the extrapyramidal symptoms ( EPS ) produced by haloperidol . Supporting the oxidative stress hypothesis , vitamin E ( antioxidant ) has demonstrated therapeutic efficacy in idiopathic parkinsonism . The prophylactic efficacy of vitamin E ( antioxidant ) on haloperidol-induced EPS was examined in a r and omized controlled trial . The sample consisted of 24 acute psychotic patients hospitalized for a 2-week trial . All patients received oral haloperidol  10 mg/day . The sample was equally r and omized to receive either haloperidol alone or haloperidol + vitamin E ( 3200 IU/day ) . EPS was rated at recruitment , both live and with video records , and on days 3 , 7 , 10 and 14 . Psychopathology was rated at recruitment and weekly thereafter . Vitamin E had no prophylactic effect on drug-induced EPS , though it did not interfere with the therapeutic efficacy of haloperidol It has been suggested that the extract of gingko biloba ( EGb ) may enhance the efficiency of the classic antipsychotic haloperidol in patients with chronic schizophrenia , especially on positive symptoms , and reduce serum superoxide dismutase ( SOD ) levels . Therefore , we decided to evaluate the therapeutic effect of EGb and to examine the effect of it on the levels of antioxidant enzymes in schizophrenic patients on olanzapine treatment . We hypothesized that EGb would have the beneficial effects on schizophrenic symptoms and might cause reductions in antioxidant enzymes . The subjects were r and omly assigned to the two groups : olanzapine plus EGb  ( group I ) ( n=15 ) and olanzapine alone  ( group II ) ( n=14 ) . The patients were evaluated at baseline and at week 8 with respect to the Positive and Negative Syndrome Scale ( PANSS ) , serum SOD , catalase ( CAT ) , and glutathion peroxidase ( GPX ) levels . At baseline , no statistically significant difference regarding the mean total PANSS scores between treatment groups was found . At the evaluation of week 8 , a significant difference in mean Scale for the Assessment of Postive Symptoms ( SAPS ) scores but not in Scale for the Assessment of Negative Symptoms scores between groups was found . Total patients had statistically significant higher serum SOD , CAT and GPX levels compared to control groups at baseline . At 8 weeks , there were significant differences in the mean decrease in SOD and CAT levels but not in GPX levels between treatment groups . The changes in SOD and CAT levels were correlated with the change in SAPS in group I , but not in the group II . The present study supported the findings of the previous study demonstrating that EGb might enhance the efficiency of antipsychotic in patients with schizophrenia , particularly on positive symptoms of the disorder OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate BACKGROUND Antipsychotics remain the mainstay of drug intervention in the management of schizophrenia . However , long-term treatment with antipsychotics is associated with a variety of movement disorders , the most disabling of which is tardive dyskinesia ( TD ) , which occurs in up to 50 % of patients hospitalized with chronic schizophrenia . The pathophysiology of TD is still unclear and no definite treatment exists . Both dopamine receptor supersensitivity and oxidative stress-induced neurotoxicity in the nigrostriatal system are apparently implicated . The pineal hormone melatonin is a potent antioxidant and attenuates dopaminergic activity in the striatum and dopamine release from the hypothalamus . Thus , it may have a beneficial effect for both the treatment and prevention of TD . METHODS Using a double-blind , placebo-controlled , crossover study , we evaluated the efficacy of 10 mg/d of melatonin for 6 weeks in 22 patients with schizophrenia and TD . The primary outcome measure was the change from baseline in Abnormal Involuntary Movement Scale ( AIMS ) score . RESULTS The decrease ( mean + /- SD ) in AIMS score was 2.45 + /- 1.92 for the melatonin and 0.77 + /- 1.11 for the placebo treatment groups ( P<.001 ) . No adverse events or side effects were noted . CONCLUSION This is the first clinical evidence for efficacy of melatonin in the treatment of TD Adherence to prescribed medications is believed to be a major problem in medicine . However , actual medication taking behaviour is rarely measured as no reliable objective measures of adherence are available . 50 mg of riboflavin administered at night could be reliably detected in urine , under UV light , for the next 18 - 24 h. The ability of 20 schizophrenic out patients to adhere to a once-a-night dosage was studied by dispensing riboflavin or placebo in a r and om sequence and testing the urine for UV fluorescence the next day . The majority of patients ( 80 % ) had errors between 40 - 80 % of the times tested . Only age and sex predicted the level of adherence . Clinicians were very poor predictors of the error rates in their patients The purpose of the study was to evaluate the effect of the classic antipsychotic haloperidol plus extract of ginkgo biloba ( EGb ) on treatment-resistant chronic schizophrenia and on blood superoxide dismutase ( SOD ) levels . Eighty-two patients with chronic refractory schizophrenia were studied . Forty-three patients were treated with haloperidol plus extract of ginkgo  biloba ( group 1 ) , and 39 received haloperidol plus placebo ( group 2 ) . SOD levels of these patients were measured before and after treatment and were compared with SOD levels of 30 healthy volunteers . Therapeutic efficiency was equated with a change in clinical rating scores assessed by st and ardized measurement tools that included the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms ( SANS ) over this period . Patients in group 1 improved significantly as demonstrated by scores from these two assessment instruments ; those in group 2 improved significantly only as shown by scores on SANS . SOD levels before treatment in all patients were significantly higher than those in healthy controls ; after treatment , the SOD level decreased significantly in group 1 but not in group 2 . These results suggest that EGb may enhance the efficiency of the classic antipsychotic haloperidol in patients with schizophrenia , especially on their positive symptoms , and that EGb may work through an antioxidant effect that is involved in the therapeutic mechanism in patients with chronic refractory schizophrenia BACKGROUND Pathomorphologic brain changes occurring as early as first-episode schizophrenia have been extensively described . Longitudinal studies have demonstrated that these changes may be progressive and associated with clinical outcome . This raises the possibility that antipsychotics might alter such pathomorphologic progression in early-stage schizophrenia . OBJECTIVE To test a priori hypotheses that olanzapine-treated patients have less change over time in whole brain gray matter volumes and lateral ventricle volumes than haloperidol-treated patients and that gray matter and lateral ventricle volume changes are associated with changes in psychopathology and neurocognition . DESIGN Longitudinal , r and omized , controlled , multisite , double-blind study . Patients treated and followed up for up to 104 weeks .  Neurocognitive and magnetic resonance imaging ( MRI ) assessment  s performed at weeks 0 ( baseline ) , 12 , 24 , 52 , and 104 . Mixed-models analyses with time-dependent covariates evaluated treatment effects on MRI end points and explored relationships between MRI , psychopathologic , and neurocognitive outcomes . SETTING Fourteen academic medical centers ( United States , 11 ; Canada , 1 ; Netherl and s , 1 ; Engl and , 1 ) . PARTICIPANTS Patients with first-episode psychosis ( DSM-IV ) and healthy volunteers . INTERVENTIONS R and om allocation to a conventional antipsychotic , haloperidol ( 2 - 20 mg/d ) , or an atypical antipsychotic , olanzapine ( 5 - 20 mg/d ) . MAIN OUTCOME MEASURES Brain volume changes assessed by MRI . RESULTS Of 263 r and omized patients , 161 had baseline and at least 1 postbaseline MRI evaluation .  Haloperidol-treated patients exhibited significant decreases in gray matter volume , whereas olanzapine-treated patients did not . A matched sample of healthy volunteers ( n = 58 ) examined contemporaneously showed no change in gray matter volume . CONCLUSIONS Patients with first-episode psychosis exhibited a significant between-treatment difference in MRI volume changes .  Haloperidol was associated with significant reductions in gray matter volume , whereas olanzapine was not . Post hoc analyses suggested that treatment effects on brain volume and psychopathology of schizophrenia may be associated . The differential treatment effects on brain morphology could be due to haloperidol-associated toxicity or greater therapeutic effects of olanzapine BACKGROUND Brain glutathione levels are decreased in schizophrenia , a disorder that often is chronic and refractory to treatment . N-acetyl cysteine ( NAC ) increases brain glutathione in rodents . This study was conducted to evaluate the safety and effectiveness of oral NAC ( 1 g orally twice daily [ b.i.d . ] ) as an add-on to maintenance medication for the treatment of chronic schizophrenia over a 24-week period . METHODS A r and omized , multicenter , double-blind , placebo-controlled study . The primary readout was change from baseline on the Positive and Negative Symptoms Scale ( PANSS ) and its components . Secondary readouts included the Clinical Global Impression ( CGI ) Severity and Improvement scales , as well as general functioning and extrapyramidal rating scales . Changes following a 4-week treatment discontinuation were evaluated . One hundred forty people with chronic schizophrenia on maintenance antipsychotic medication were r and omized ; 84 completed treatment . RESULTS Intent-to-treat analysis revealed that subjects treated with NAC improved more than placebo-treated subjects over the study period in PANSS total [ -5.97 ( -10.44 , -1.51 ) , p = .009 ] , PANSS negative [ mean difference -1.83 ( 95 % confidence interval : -3.33 , -.32 ) , p = .018 ] , and PANSS general [ -2.79 ( -5.38 , -.20 ) , p = .035 ] , CGI-Severity ( CGI-S ) [ -.26 ( -.44 , -.08 ) , p = .004 ] , and CGI-Improvement ( CGI-I ) [ -.22 ( -.41 , -.03 ) , p = .025 ] scores . No significant change on the PANSS positive subscale was seen . N-acetyl cysteine treatment also was associated with an improvement in akathisia ( p = .022 ) . Effect sizes at end point were consistent with moderate benefits . CONCLUSIONS These data suggest that adjunctive NAC has potential as a safe and moderately effective augmentation strategy for chronic schizophrenia OBJECTIVE The authors ' goal was to test the efficacy of selegiline augmentation of antipsychotic medication in out patients with schizophrenia who had negative symptoms of moderate or greater severity . METHOD A 12-week , double-blind , placebo-controlled , multicenter trial of oral selegiline augmentation 
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Adverse events were generally poorly reported .
No evidence was available for relapse , quality of life or service use .