***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 
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    Input: A double-blind withdrawal trial in 41 chronic schizophrenic out patients was carried out during 6 months . Depot neuroleptics ( fluphenazine decanoate or flupenthixol decanoate ) were compared with placebo to evaluate clinical and neurological effects during continued therapy and during withdrawal . The drugs were significantly more effective than placebo in preventing relapse and rehospitalization . In the placebo group 62 % relapsed compared to 27 % in the drug group . There was a weak and nonsignificant tendency to a higher relapse frequency in the flupenthixol group compared to the fluphenazine group . After withdrawal for 6 months , plasma levels for fluphenazine were detectable . Plasma levels for flupenthixol  were not detectable after 9 weeks of withdrawal . The differences in the plasma levels may possibly explain the difference in relapse rate between the two depot neuroleptics . Furthermore , it was found that the patients who relapsed during fluphenazine treatment had a significantly lower plasma level of the drug than patients who did not relapse during treatment . The results from this study provide some information on the therapeutic levels of fluphenazine and flupenthixol in schizophrenic patients Out of 253 patients fulfilling criteria for a first episode of schizophrenic illness , 120 entered a r and omised placebo-controlled trial of maintenance neuroleptic medication on discharge ; they were followed to relapse or loss to follow-up , for two years or to the end of the study . Of those on active medication , 46 % relapsed , as did 62 % of those on placebo ; the most important determinant of relapse was duration of illness prior to starting neuroleptic medication . This finding might be because extended duration of symptoms before admission is more likely to be present in illnesses which in any case will have poor prognosis , or because susceptibility to relapse is reduced by early institution of treatment . The study provides no data on which a decision between these alternative explanations can be based 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 The study investigated the non-inferiority of flupentixol compared to risperidone in the treatment of negative symptoms . In addition , the effects of flupentixol on mood and cognitive symptoms were explored . In a r and omized , double-blind multicenter study , 144 non-acute schizophrenia patients with predominant negative symptoms were treated with a flexible dose of either flupentixol ( 4 - 12 mg/d ) or risperidone ( 2 - 6 mg/d ) for up to 25 weeks . In addition to a non-inferiority analysis , a principal component analysis ( PCA ) of the PANSS was performed post hoc . Regarding negative symptoms , flupentixol proved to be non-inferior to risperidone . Both drugs improved depressed mood with effect sizes favoring flupentixol . PCA suggested a five-factor structure . Effect sizes for the cognitive factor were up to 0.74 for flupentixol and up to 0.80 for risperidone .  EPS scores were rather low and Parkinsonism improved in both groups , but anticholinergic drugs were prescribed significantly more frequently in the flupentixol group , which generally showed significantly more adverse events . Results indicate that the 1st generation antipsychotic flupentixol  improves negative , affective and cognitive symptoms in chronic schizophrenia comparable to risperidone . Further studies should confirm the latter using neuropsychological performance tests and should investigate whether tolerability improves with a markedly lower dose range Urinary MHPG excretion in patients with acute schizophrenia was studied before and during a trial of the isomers of flupenthixol and placebo . Pretrial MHPG excretion was not related to severity of illness before the trial or to other pretrial clinical variables . In male subjects higher pretrial MHPG excretion was associated with a better outcome 1 year post-trial . However in females no relationship between MHPG excretion and outcome was established . During the trial there was a reduction in MHPG excretion in patients treated with β-flupenthixol but no decrease in the group treated with α-flupenthixol or chlorpromazine . In patients on placebo  there was a reduction in MHPG excretion in those who dit well clinical ly , but not in those who did poorly . Thus low MHPG excretion may be a predictor of poor outcome in schizophrenia , but MHPG excretion also changes both as a function of clinical state and of neuroleptic drug administration Fifty‐six out of 60 schizophrenic patients completed a double‐blind study of two long‐acting neuroleptics , penfluridol ( peroral ) and flupenthixol decanoate ( parenteral ) . Half of the patients were on maintenance . therapy of flupenthixol prior to the study , the other half on penfluridol . The actual double‐blind study ( 12 weeks ) was commenced after a preliminary period of 4 weeks , the patients in the two main groups being r and omly divided into two further groups , one continuing the medication unchanged , the other changing to the alternative drug The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more .  ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas Forty-five patients with acute schizophrenic illnesses ( defined by PSE criteria ) were assessed in clinical , cognitive and social terms before being entered in a four week study of the isomers of flupenthixol and placebo . At the end of one year they were re-assessed in the same terms . The clinical and psychological features of the acute illness and the drug treatment given did not predict outcome . Poor outcome in social terms was significantly related to severe social isolation in the initial assessment and to the presence of nuclear symptoms and negative schizophrenic features at follow-up In a double-blind trial in which 45 patients with acute schizophrenia took part the alpha-isomer of flupenthixol  ( which blocks the dopamine receptor ) was found to be significantly more effective than both beta-flupenthixol ( which does not ) and placebo . The drug effect was confined to the " positive " symptoms -- delusions , hallucinations , and though disorder-- and appeared only in the 3rd and 4th weeks of the trial . It was as great in patients with evidence of deterioration ( Feighner-positive patients ) as in patients without deterioration and was less in patients who had affective disturbance in addition to schizophrenia symptoms . The findings are consistent with the hypothesis that dopamine-receptor blockade is the only requirement for antipsychotic activity and suggest that the antipsychotic effect occurs in patients with typically schizophrenic illnesses but may be limited to positive symptoms Changes in levels of prolactin , growth hormone , luteinizing hormone , and follicle stimulating hormone in serum , and testosterone in plasma , have been studied in 38 patients with acute schizophrenic illnesses in a 4-week double-blind comparison of the 2 isomers of flupenthixol and placebo . Only prolactin showed changes which could be related either to changes in clinical state or to the effects of medication . Prolactin levels increased during treatment with the therapeutically active alpha-isomer of flupenthixol but were unchanged with the inactive beta-isomer and placebo . Although there was a significant relationship between prolactin level and antipsychotic effect in patients on alpha-flupenthixol  , in the individual case prolactin level was not a strong predictor of therapeutic response ; and in patients on inactive medication changes in prolactin level could not be related to sympton change . There was a time lag of at least 2 weeks between the increase in prolactin secretion in patients on alpha-flupenthixol and the therapeutic effect attributable to medication . This delay suggests that if the antipsychotic effect is dependent upon dopamine receptor blockade it is not a direct consequence of this action . Perhaps dopamine receptor blockade permits other , and slower , changes to take place and it is these changes , rather than dopamine receptor blockade itself , which are reflected in clinical improvement Abstract The benzamide amisulpride ( ASP ) is a selective D2-like dopamine antagonist , while flupentixol ( FPX ) , a thioxanthene , blocks D2-like , D1-like and 5-HT2 receptors . To evaluate efficacy and safety of ASP and to investigate the importance of an additional D1-like antagonism for antipsychotic effects and extrapyramidal tolerability , a r and omized double-blind multi-center study versus FPX as reference drug was performed for 6 weeks in 132 patients suffering from acute schizophrenia ( DSM-III-R ) with predominant positive symptomatology . Doses were initially fixed ( ASP : 1000 mg/day ; FPX : 25 mg/day ) but could be reduced by 40 % in case of side effects ( mean daily doses : ASP : 956 mg ; FPX : 22.6 mg ) . Intention-to-treat evaluation demonstrated significant improvement under both medications . The difference between the mean BPRS decreases of both treatment groups was 5.6 points ( 95 % CI : 0.55 ; 10.65 ) in favour of ASP . According to CGI , 62 % of patients in either drug group were treatment responders . ANCOVA analysis showed that reductions of BPRS ( ASP : −42 % ; FPX : −32 % ) and SAPS ( ASP : −78 % ; FPX : −65 % ) were more pronounced under ASP . Due to adverse events , significantly fewer ASP patients ( 6 % ) were withdrawn from the study ( FPX : 18 % ) . Extrapyramidal tolerability was better in the ASP group , as demonstrated by smaller increases in the Simpson-Angus Scale , the AIMS , and the Barnes Akathisia Scale in ANCOVA analyses with dosage as covariate . ASP appears to be as effective as FPX with regard to antipsychotic effects on positive schizophrenic symptomatology , while extrapyramidal tolerability is better . These conclusions have to be drawn cautiously , as dosage effects on outcome parameters can not be entirely ruled out . The present results question the notion that additional blockade of D1-like receptors may be necessary to achieve sufficient antipsychotic effects or to improve extrapyramidal tolerability CMAJ • MAY 12 , 2009 • 180(10 ) © 2009 Canadian Medical Association or its licensors E47 R and omized trials have traditionally been broadly categorized as either an effectiveness trial or an efficacy trial , although we prefer the terms “ pragmatic ” and “ explanatory . ” Schwartz and Lellouch described these 2 approaches toward clinical trials in 1967 . These authors coined the term “ pragmatic ” to describe trials that help users choose between options for care , and “ explanatory ” to describe trials that test causal research hypotheses ( i.e. , that a given intervention causes a particular benefit ) . We take the view that , in general , pragmatic 
    Output:
    
We found no clear data on mental state and behaviour , adverse effects , service use , satisfaction with treatment or costs .