title: Aggression and psychopathology in treatment-resistant inpatients with schizophrenia and schizoaffective disorder. What does the PANSS mean? Neurocognitive effects of clozapine, olanzapine, risperidone, and haloperidol in patients with chronic schizophrenia or schizoaffective disorder. Components of variance and intraclass correlations for the design of community-based surveys and intervention studies: data from the Health Survey for England 1994. Benzodiazepines for psychosis-induced aggression or agitation. Depression and impulsivity as pathways to violence: implications for antiaggressive treatment. Effects of atypical antipsychotics on the syndromal profile in treatment-resistant schizophrenia. Effects of clozapine, olanzapine, risperidone, and haloperidol on hostility among patients with schizophrenia. Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder. Atypical Antipsychotics, Neurocognitive Deficits, and Aggression in Schizophrenic Patients Changes in glucose and cholesterol levels in patients with schizophrenia treated with typical or atypical antipsychotics. Prolactin levels in schizophrenia and schizoaffective disorder patients treated with clozapine, olanzapine, risperidone, or haloperidol. Overt Aggression and Psychotic Symptoms in Patients With Schizophrenia Treated With Clozapine, Olanzapine, Risperidone, or Haloperidol Unpublished rating scales: a major source of bias in randomised controlled trials of treatments for schizophrenia. Executive function predicts response to antiaggression treatment in schizophrenia: a randomized controlled trial.
abstract: Positive psychotic symptoms , such as threat/"control-override " delusions or comm and hallucinations , have been related to aggression in patients with schizophrenia . However , retrospective data collection has hampered evaluation of the direct influence of psychopathology on aggressive behavior . In this study , we monitored aggressive behavior and psychopathology prospect ively and in close temporal proximity in 157 treatment-resistant in patients diagnosed with chronic schizophrenia or schizoaffective disorder participating in a 14-week double-blind clinical trial . Aggressive behavior was rated with the overt aggression scale ( OAS ) . Psychopathology was assessed using the positive and negative syndrome scale ( PANSS ) . At baseline , subjects who would be aggressive during the study had higher scores on only two PANSS items : hostility and poor impulse control . During the study PANSS positive subscale scores were significantly higher in aggressive subjects . Total PANSS scores were higher within 3 days of an aggressive incident , as were positive and general psychopathology subscale scores . However , in a smaller sub sample for whom PANSS ratings were available within 3 days before aggressive incidents , only scores on the PANSS positive subscale were significantly higher . These findings in chronic , treatment resistant in patients support the view that positive symptoms may lead to aggression 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 OBJECTIVE Newer antipsychotic drugs have shown promise in ameliorating neurocognitive deficits in patients with schizophrenia , but few studies have compared newer antipsychotic drugs with both clozapine and conventional agents , particularly in patients who have had suboptimal response to prior treatments . METHOD The authors examined the effects of clozapine , olanzapine , risperidone , and haloperidol on 16 measures of neurocognitive functioning in a double-blind , 14-week trial involving 101 patients . A global score was computed along with scores in four neurocognitive domains : memory , attention , motor function , and general executive and perceptual organization . RESULTS Global neurocognitive function improved with olanzapine and risperidone treatment , and these improvements were superior to those seen with haloperidol . Patients treated with olanzapine exhibited improvement in the general and attention domains but not more than that observed with other treatments . Patients treated with risperidone exhibited improvement in memory that was superior to that of both clozapine and haloperidol . Clozapine yielded improvement in motor function but not more than in other groups . Average effect sizes for change were in the small to medium range . More than half of the patients treated with olanzapine and risperidone experienced " clinical ly significant " improvement ( changes in score of at least one-half st and ard deviation relative to baseline ) . These findings did not appear to be mediated by changes in symptoms , side effects , or blood levels of medications . CONCLUSIONS Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs , and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects 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 BACKGROUND Acute psychotic illness , especially when associated with agitated or violent behaviour , can require urgent pharmacological tranquillisation or sedation . In several countries , clinicians often use benzodiazepines ( either alone or in combination with antipsychotics ) for this outcome . OBJECTIVES To estimate the effects of benzodiazepines , alone or in combination with antipsychotics , when compared with placebo or antipsychotics , alone or in combination with antihistamines , to control disturbed behaviour and reduce psychotic symptoms . SEARCH METHODS We search ed the Cochrane Schizophrenia Group 's register ( January 2012 ) , inspected reference lists of included and excluded studies and contacted authors of relevant studies . SELECTION CRITERIA We included all r and omised clinical trials ( RCTs ) comparing benzodiazepines alone or in combination with any antipsychotics , versus antipsychotics alone or in combination with any other antipsychotics , benzodiazepines or antihistamines , for people with acute psychotic illnesses . DATA COLLECTION AND ANALYSIS We reliably selected studies , quality assessed them and extracted data . For binary outcomes , we calculated st and ard estimates of relative risk ( RR ) and their 95 % confidence intervals ( CI ) using a fixed-effect model . For continuous outcomes , we calculated the mean difference ( MD ) between groups . If heterogeneity was identified , this was explored using a r and om-effects model . MAIN RESULTS We included 21 trials with a total of n = 1968 participants . There was no significant difference for most outcomes in the one trial that compared benzodiazepines with placebo , although there was a higher risk of no improvement in people receiving placebo in the medium term ( one to 48 hours ) ( n = 102 , 1 RCT , RR 0.62 , 95 % CI 0.40 to 0.97 , very low quality evidence ) . There was no difference in the number of participants who had not improved in the medium term when benzodiazepines were compared with antipsychotics ( n = 308 , 5 RCTs , RR 1.10 , 95 % CI 0.85 to 1.42 , low quality evidence ) ; however , people receiving benzodiazepines were less likely to experience extrapyramidal effects ( EPS ) in the medium term ( n = 536 , 8 RCTs , RR 0.15 , 95 % CI 0.06 to 0.39 , moderate quality of evidence ) . Data comparing combined benzodiazepines and antipsychotics versus benzodiazepines alone did not yield any significant results . When comparing combined benzodiazepines/antipsychotics ( all studies compared haloperidol ) with the same antipsychotics alone ( haloperidol ) , there was no difference between groups in improvement in the medium term ( n = 155 , 3 RCTs , RR 1.27 , 95 % CI 0.94 to 1.70 , very low quality evidence ) but sedation was more likely in people who received the combination therapy ( n = 172 , 3 RCTs , RR 1.75 , 95 % CI 1.14 to 2.67 , very low quality evidence ) . However , more participants receiving combined benzodiazepines and haloperidol had not improved by medium term when compared to participants receiving olanzapine ( n = 60,1 RCT , RR 25.00 , 95 % CI 1.55 to 403.99 , very low quality evidence ) or ziprasidone ( n = 60 , 1 RCT , RR 4.00 , 95 % CI 1.25 to 12.75very low quality evidence ) . When haloperidol and midazolam were compared with olanzapine , there was some evidence the combination was superior in terms of improvement , sedation and behaviour . AUTHORS ' CONCLUSIONS The evidence from trials for the use of benzodiazepines alone is not good . There were relatively little good data and most trials are too small to highlight differences in either positive or negative effects . Adding a benzodiazepine to other drugs does not seem to confer clear advantage and has potential for adding unnecessary adverse effects . Sole use of older antipsychotics unaccompanied by anticholinergic drugs seems difficult to justify . Much more high quality research is needed in this area BACKGROUND Difficulties with affect regulation and impulse control have a strong influence on violence . The objective of this study was to determine whether baseline depression and impulsivity predict aggression and whether they predict differential response to antiaggressive treatment . This is important , as we lack knowledge as to the selection of antipsychotics for the treatment of aggression . METHODS Physically aggressive in patients with schizophrenia who received an evaluation of depression and impulsivity at baseline were r and omly assigned in a double-blind , parallel group , 12-week trial to clozapine , olanzapine , or haloperidol . Trait impulsivity was measured by the Barratt Impulsiveness Scale ; depression by the Positive and Negative Syndrome Scale Depression factor . The number and severity of aggressive events , as measured by the Modified Overt Aggression Scale ( MOAS ) , were the outcome measures . RESULTS Baseline depression and impulsivity predicted higher levels of aggression , as measured by the MOAS total score , over the 12-week treatment period across all 3 medication groups . In addition , there was a strong interaction effect between baseline depression/impulsivity and medication grouping in predicting MOAS score . In particular , when higher depression and impulsivity were present at baseline , patients on haloperidol presented with more aggression than patients on the other 3 medications . CONCLUSIONS Depression and impulsivity are important predictors of aggression and of differential response to antiaggressive treatment . This is most likely due to the medications ' dissimilar neurotransmitter profiles . By identifying patients who will respond better to a given medication , we will be able to develop individualized strategies for the treatment of violent behavior BACKGROUND There has been considerable support for the observation that atypical antipsychotics have a broader range of therapeutic effects than traditional antipsychotics . We are exploring whether this exp and ed clinical efficacy can also be seen in patients with treatment-resistant schizophrenia . METHOD The subjects were 157 treatment-resistant in patients diagnosed with DSM-IV schizophrenia or schizoaffective disorder . They were r and omly assigned to treatment with clozapine , olanzapine , risperidone , or haloperidol in a 14-week double-blind trial and rated with a st and ard measure of clinical antipsychotic efficacy ( Positive and Negative Syndrome Scale [ PANSS ] ) . Factor analysis at baseline and endpoint together with changes in 5 PANSS-derived factors were examined . Data were gathered from June 1996 to December 1999 . RESULTS The underlying PANSS factor structure , as indicated by the factor loadings , was essentially identical at baseline and endpoint . At baseline , the excitement factor was followed by the positive , negative , cognitive , and depression/anxiety factors , explaining 49.4 % of the total variance . At endpoint , the positive factor was followed by the negative , excitement , cognitive , and depression/anxiety factors , explaining 55.5 % of the total variance . The endpoint data indicated statistically significant ( p < .05 ) improvements over time on the positive factor for all 3 atypicals , but not for haloperidol . The negative factor showed significant improvement for clozapine and olanzapine , with significant worsening for haloperidol . Clozapine , olanzapine , and risperidone were superior to haloperidol on the negative factor , while clozapine was also superior to risperidone . The cognitive factor showed significant improvement for all atypicals , as did the depression/anxiety factor . Only clozapine showed improvement on the excitement factor and was superior to both haloperidol and risperidone . CONCLUSIONS Treatment with atypical antipsychotics did not substantially change the underlying PANSS 5-factor structure . However , antipsychotic treatment with all 3 atypical medications was associated with significant improvements on 3 of 5 syndromal domains ( positive , cognitive , and depression/anxiety ) of schizophrenia . Clozapine and olanzapine also showed improvement on the negative factor . Only clozapine was associated with improvement on the excitement domain . This finding confirms that atypicals are associated with improvement of an exp and ed spectrum of symptoms in treatment-resistant patients OBJECTIVE This study compared the specific antiaggressive effects of clozapine with those of olanzapine , risperidone , and haloperidol . METHODS A total of 157 in patients with schizophrenia or schizoaffective disorder and a history of suboptimal treatment response were r and omly assigned to receive clozapine , olanzapine , risperidone , or haloperidol in a double-blind 14-week trial . The trial was divided into two periods : eight weeks during which the dosage was escalated and then fixed , and six weeks during which variable dosages were used . The hostility item of the Positive and Negative Syndrome Scale ( PANSS ) was the principal outcome measure . Covariates included the items that reflect positive symptoms of schizophrenia ( delusions , suspiciousness or feelings of persecution , gr and iosity , unusual thought content , conceptual disorganization , and hallucinations ) and the sedation item of the Nurses Observation Scale for Inpatient Evaluation ( NOSIE ) . RESULTS Patients differed in their treatment response as measured by the hostility item of the PANSS . The scores of patients taking clozapine indicated significantly greater improvement than those of patients taking haloperidol or risperidone . The effect on hostility appeared to be independent of the antipsychotic effect of clozapine on other PANSS items that reflect delusional thinking , a formal thought disorder , or hallucinations and independent of sedation as measured by the NOSIE . Neither risperidone nor olanzapine showed superiority to haloperidol . CONCLUSION Clozapine has a relative advantage over other antipsychotics as a specific antihostility agent CONTEXT Violent behavior of patients with schizophrenia prolongs hospital stay and interferes with their integration into the community . Finding appropriate treatment of violent behaviors is of primary importance . OBJECTIVE To compare the efficacy of 2 atypical antipsychotic agents , clozapine and olanzapine , with one another and with haloperidol in the treatment of physical assaults and other aggressive behaviors in physically assaultive patients with schizophrenia and schizoaffective disorder . DESIGN AND SETTING R and omized , double-blind , parallel-group , 12-week trial . Physically assaultive subjects with schizophrenia or schizoaffective disorder who were in patients in state psychiatric facilities were r and omly assigned to treatment with clozapine ( n = 37 ) , olanzapine ( n = 37 ) , or haloperidol ( n = 36 ) . MAIN OUTCOME MEASURES Number and severity of physical assaults as measured by the Modified Overt Aggression Scale ( MOAS ) physical aggression score and the number and severity of all aggressive events as measured by the MOAS overall score . Psychiatric symptoms were assessed through the Positive and Negative Syndrome Scale ( PANSS ) . RESULTS Clozapine was superior to both olanzapine and haloperidol in reducing the number and severity of physical assaults as assessed by the MOAS physical aggression score and in reducing overall aggression as measured by the MOAS total score . Olanzapine was superior to haloperidol in reducing the number and severity of aggressive incidents on these 2 MOAS measures . There were no significant differences among the 3 medication groups in improvement of psychiatric symptoms as measured by the PANSS total score and the 3 PANSS subscales . CONCLUSIONS Clozapine shows greater efficacy than olanzapine and olanzapine greater efficacy than haloperidol in reducing aggressive behavior . This antiaggressive effect appears to be separate from the antipsychotic and sedative action of these medications The purpose of this study was to compare the effects of olanzapine , clozapine , and haloperidol on neurocognitive function in schizophrenic patients who present with documented episodes of physical aggression and to determine whether change in cognitive function is related to aggression . One hundred physically aggressive schizophrenic in patients were assigned to a r and omized , double-blind , parallel-group , 12-week treatment , and received cognitive evaluations at baseline . There were 33 , 34 , and 33 subjects in the clozapine , olanzapine , and haloperidol groups , respectively . They were administered a battery of tests assessing psychomotor function , general executive function , visual and verbal memory , and visuospatial ability . A general cognitive index was derived from the above battery . The overall score on the Modified Overt Aggression Scale was used to measure the number and severity of the aggressive events . Psychiatric symptoms and side effects were also assessed . The improvement in the general cognitive index differed significantly among the 3 treatment groups , with olanzapine being superior to both haloperidol and clozapine . Further analyses revealed significantly greater improvement with olanzapine in several cognitive domains . Furthermore , improvement in the general cognitive index was significantly associated with a decrease in aggression in the olanzapine group but not in the other 2 medication groups . In violent schizophrenic patients , olanzapine treatment is associated with better cognitive functioning relative to haloperidol and clozapine . This improvement in neurocognitive function is associated with a decrease in aggressive behavior . As clozapine markedly reduced aggression , there may be different pathways for the antiaggressive effect of olanzapine and that of clozapine OBJECTIVE The association of hyperglycemia and hypercholesterolemia with use of atypical antipsychotics has been documented in case reports and uncontrolled studies . The authors ' goal was to assess the effects of clozapine , olanzapine , risperidone , and haloperidol on glucose and cholesterol levels in hospitalized patients with schizophrenia or schizoaffective disorder during a r and omized double-blind 14-week trial . METHOD One hundred fifty-seven patients with schizophrenia or schizoaffective disorder who were in patients at four hospitals were originally included in the study . The 14-week trial consisted of an 8-week fixed-dose period and a 6-week variable-dose period . Planned assessment s included fasting glucose and cholesterol , which were collected at baseline and at the end of the 8-week period and the following 6-week period . RESULTS One hundred eight of the 157 patients provided blood sample s at baseline and at least at one point after r and om assignment to clozapine , olanzapine , risperidone , or haloperidol during the treatment trial . Seven of these patients had diabetes ; their glucose levels were > 125 mg/dl at baseline . Data from 101 patients were used for statistical analyses . During the initial 8-week period there was an overall significant increase in mean glucose levels . There were significant increases in glucose levels at the end of the 8-week fixed-dose period for patients given clozapine ( N=27 ) and those given haloperidol ( N=25 ) . The olanzapine group showed a significant increase of glucose levels at the end of the 6-week variable-dose period ( N=22 ) . Fourteen of the 101 patients developed abnormal glucose levels ( > 125 mg/dl ) during the trial ( six with clozapine , four with olanzapine , three with risperidone , and one with haloperidol ) . Cholesterol levels were increased at the end of the 8-week fixed-dose period for the patients given clozapine ( N=27 ) and those given olanzapine ( N=26 ) ; cholesterol levels were also increased at the end of the 6-week variable-dose period for patients given olanzapine ( N=22 ) . CONCLUSIONS In this prospect i ve r and omized trial , clozapine , olanzapine , and haloperidol were associated with an increase of plasma glucose level , and clozapine and olanzapine were associated with an increase in cholesterol levels . The mean changes in glucose and cholesterol levels remained within clinical ly normal ranges , but approximately 14 % of the patients developed abnormally high glucose levels during the course of their participation in the study BACKGROUND Prolactin levels are elevated to varying degrees by antipsychotics . Prolactin elevations may result in sexual and other adverse effects , and they may be related to antipsychotic effects . We used the data collected in a trial of antipsychotics to study the differential effect of these drugs on prolactin level , to explore the relation between clinical effects and prolactin level , and to determine the relationship between plasma levels of antipsychotics and prolactin level . METHOD Treatment-resistant patients ( 133 men , 24 women ) diagnosed with DSM-IV schizophrenia or schizoaffective disorder participated in a double-blind , r and omized , 14-week trial comparing clozapine ( N = 40 ) , olanzapine ( N = 39 ) , risperidone ( N = 41 ) , and haloperidol ( N = 37 ) . Plasma levels of prolactin and antipsychotics were determined at baseline and at weeks 5 , 8 , 10 , 12 , and 14 during the trial . Clinical effects were measured with the Positive and Negative Syndrome Scale and the Extrapyramidal Symptom Rating Scale . Statistical analyses were limited to the 75 men for whom repeated prolactin levels were available . Data were gathered from June 1996 to December 1999 . RESULTS Risperidone caused significant elevation of prolactin levels ( p < .05 ) that appeared to be dose-dependent . Clozapine and olanzapine were associated with decreases of prolactin , whereas haloperidol led to a minor , nonsignificant increase . Plasma olanzapine and prolactin levels were correlated . Prolactin levels were not related to clinical improvement or extrapyramidal side effects . CONCLUSION Antipsychotics show major differences in their effects on prolactin , and risperidone has clearly the most robust effect Abstract : The subjects were 157 treatment-resistant in patients diagnosed with chronic schizophrenia or schizoaffective disorder . They were r and omly assigned to treatment with clozapine , olanzapine , risperidone , or haloperidol in a 14-week , double-blind trial . Incidents of overt aggression were recorded and their severity was scored . The Positive and Negative Syndrome Scale was administered . Atypical antipsychotics showed an overall superiority over haloperidol , particularly after the first 24 days of the study when the dose escalation of clozapine was completed . Once an adequate therapeutic dose of clozapine was reached , it was superior to haloperidol in reducing the number and severity of aggressive incidents . Patients exhibiting persistent aggressive behavior showed less improvement of psychotic symptoms than the other patients . There was an interaction between aggressiveness , medication type , and antipsychotic response : risperidone and olanzapine showed better antipsychotic efficacy in patients exhibiting less aggressive behavior ; the opposite was true for clozapine . Clozapine appears to have superior antiaggresive effects in treatment-resistant patients ; this superiority develops after the patient has been exposed to an adequate dose regimen BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales  were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials OBJECTIVE Despite extensive experience with antipsychotic medications , we have limited capacity to predict which patients will benefit from which medications and for what symptoms . Such prediction is of particular importance for the proper treatment of violence . Our goal was to determine whether executive function predicts outcome of treatment for aggressive behavior and whether such prediction varies across medication groups . METHOD Ninety-nine physically aggressive in patients ( aged 18 - 60 years ) with schizophrenia or schizoaffective disorder ( diagnosed according to DSM-IV ) who completed tests of executive function were r and omly assigned in a double-blind , parallel-group , 12-week trial to clozapine ( n = 32 ) , olanzapine ( n = 32 ) , or haloperidol ( n = 35 ) . The number and severity of aggressive events as measured by the Modified Overt Aggression Scale ( MOAS ) were the outcome measures . Psychopathology and medication side effects were also assessed . The study was conducted from 1999 to 2004 . RESULTS Poor executive function predicted higher levels of aggression , as measured by MOAS scores over the 12-week period , in all 3 medication groups ( F(1,98 ) = 222.2 , P < .0001 ) . There was , however , a significant interaction effect between medication grouping and executive function ( F(1,98 ) = 15.32 , P < .001 ) : clozapine exerted an antiaggression effect even in the presence of executive dysfunction . CONCLUSIONS Executive function was a strong predictor of response to antiaggression treatment in all medication groups , but clozapine still retained clinical efficacy in the presence of poor executive functioning . Olanzapine was particularly efficacious in the absence of executive dysfunction . These findings have important implication s for a targeted approach to the treatment of aggression in patients with schizophrenia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01123408
target: MAIN RESULTS We have no good- quality evidence of the absolute effectiveness of haloperidol for people with long-term aggression .
  When haloperidol was compared with olanzapine or clozapine , skewed data ( n=83 ) at high risk of bias suggested some advantage in terms of scale scores of unclear clinical meaning for olanzapine/clozapine for ' total aggression ' .
  Although there were some data for the outcomes listed above , there were no data on most of the binary outcomes and none on service outcomes ( use of hospital/police ) , satisfaction with treatment , acceptance of treatment , quality of life or economics .
background: BACKGROUND Psychotic disorders can lead some people to become agitated .
  Characterised by restlessness , excitability and irritability , this can result in verbal and physically aggressive behaviour - and both can be prolonged .
  Aggression within the psychiatric setting imposes a significant challenge to clinicians and risk to service users ; it is a frequent cause for admission to inpatient facilities .
  If people continue to be aggressive it can lengthen hospitalisation .
  Haloperidol is used to treat people with long-term aggression .
  OBJECTIVES To examine whether haloperidol alone , administered orally , intramuscularly or intravenously , is an effective treatment for long-term/persistent aggression in psychosis .