Use of antipsychotics and benzodiazepines in patients with psychiatric emergencies: Results of an observational trial Current practices in managing acutely disturbed patients at three hospitals in Rio de Janeiro-Brazil: a prevalence study Overt Aggression and Psychotic Symptoms in Patients With Schizophrenia Treated With Clozapine, Olanzapine, Risperidone, or Haloperidol Comparative study of the effectiveness of zuclopenthixol acetate and haloperidol in acutely disturbed psychotic patients. Intramuscular flunitrazepam versus intramuscular haloperidol in the emergency treatment of aggressive psychotic behavior. Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder. Comparison of Risperidone Orodispersible Tablet and Intramuscular Haloperidol in the Treatment of Acute Psychotic Agitation: A Randomized Open, Prospective Study Long-term maintenance therapy with quetiapine versus haloperidol decanoate in patients with schizophrenia or schizoaffective disorder. Quality of life during treatment with haloperidol or olanzapine in the year following a first psychotic episode Asian outpatients with schizophrenia: a double-blind randomized comparison of quality of life and clinical outcomes for patients treated with olanzapine or haloperidol. Olanzapine versus haloperidol in the treatment of schizophrenia and other psychotic disorders: Quality of life and clinical outcomes of a randomized clinical trial Rapid tranquillisation in psychiatric emergency settings in Brazil: pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine Rapid Tranquilization of Severely Agitated Patients With Schizophrenia Spectrum Disorders: A Naturalistic, Rater-Blinded, Randomized, Controlled Study With Oral Haloperidol, Risperidone, and Olanzapine Rapid tranquilization for agitated patients in emergency psychiatric rooms: a randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone. Rapid treatment of acute psychotic symptoms with high- and low-dose haloperidol. Behavioral considerations. Plasma/RBC haloperidol ratios and improvement in acute psychotic symptoms. Predictors of therapeutic response to haloperidol in acute schizophrenia.
Background Conventional antipsychotics augmented with benzodiazepines have been the st and ard acute treatment for psychiatric emergencies for more than 50 years . The inability of patients to give informed consent limits r and omised , controlled studies . This observational study on immediate therapy for aggression and impulse control in acutely agitated patients ( IMPULSE ) evaluated the short-term effectiveness and tolerability of atypical and typical antipsychotic medications ( AP ) in a non-interventional setting . Methods This was a comparative , non-r and omised , prospect i ve , open-label , observational study . Treatment over the first 5 days was classified according to whether any olanzapine , risperidone , or haloperidol was included or not . Documentations ( PANSS-excited component , CGI-aggression , CGI-suicidality , tranquilisation score ) were at baseline ( day 1 ) and days 2–6 after start of AP . Results During the short treatment-period , PANSS-EC and CGI-aggression scores improved in all cohorts . 68.7 % of patients treated with olanzapine , 72.2 % of patients treated with risperidone , and 83.3 % of patients treated with haloperidol received concomitant benzodiazepines ( haloperidol vs. non-haloperidol : p < 0.001 ) . More patients treated with olanzapine ( 73.8 % ) were fully alert according to a tranquilisation score and active at day 2 than patients treated with risperidone ( 57.1 % ) or haloperidol ( 58.0 % ) . Conclusion Current medication practice s for immediate aggression control are effective with positive results present within a few days . In this study , concomitant benzodiazepine use was significantly more frequent in patients receiving haloperidol Background The medical management of aggressive and violent behaviour is a critical situation for which there is little evidence . In order to prepare for a r and omised trial , due to start in the psychiatric emergency rooms of Rio de Janeiro in 2001 , a survey of current practice was necessary . Methods A seven day survey of pharmacological management of aggressive people with psychosis in the emergency rooms of all four public psychiatric hospitals in Rio de Janeiro , Brazil . Results In one hospital data were not available . Of the 764 people with psychosis attending these ERs , 74 were given IM medication for rapid tranquillisation ( 9.7 % , 2.1/week/100,000 ) . A haloperidol-promethazine mix ( with or without other drugs ) was used for the majority of patients ( 83 % ) . Conclusion The haloperidol-promethazine mix , given intramuscularly for rapid tranquilization , is prevalent in Rio , where it is considered both safe and efficient . However , scientific evaluation of all pharmacological approaches to rapid tranquilization of psychotic people is inadequate or incomplete and a r and omized trial of IM haloperidol-promethazine is overdue 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 OBJECTIVES To study the effectiveness , frequency of administration and side effects of zuclopenthixol acetate ( ZPTA ) and haloperidol ( HAL ) in the treatment of acute psychotic disturbance with aggression . METHOD Purposive sampling method was employed in a group of psychotic patients with aggression admitted to Songkla Neuropsychiatric Hospital , they were r and omly divided into 2 groups :  ZPTA  group and HAL group . All of the patients were evaluated daily for 7 consecutive days using the Brief Psychiatric Rating Scale ( BPRS ) and the Clinical Global Impression Scale ( CGI ) . Statistical analysis was performed by using the Student t-test and Linear regression . RESULTS There were 70 patients with diagnosis of schizophrenia , mania and acute psychosis . Thirty-eight patients were r and omly assigned to the ZPTA group and were given 50 - 100 mg of the drug , while 32 patients received HAL 5 - 10 mg . The result showed a significant reduction in BPRS or CGI scores in both groups . Patients treated with ZPTA required less frequent administration than did those on HAL ( p < 0.05 ) . There was no statistically significant difference in the reduction in scores between the two groups . Nor was there a statistical difference in reduction of aggression based on BPRS rating . Each group of patients showed a few side effects of mild degree . CONCLUSION Both ZPTA and HAL were effective in the treatment of acute psychosis with aggression , but frequency of administration was lower in the ZPTA OBJECTIVE The authors examined the efficacy of intramuscular flunitrazepam compared with intramuscular haloperidol for the immediate control of agitated or aggressive behavior in acutely psychotic patients . METHOD Twenty-eight actively psychotic in patients , aged 20 - 60 years , who were under treatment with neuroleptic agents were selected for the study . Each was r and omly assigned on a double-blind basis to receive either 5 mg i.m . of haloperidol ( N=13 ) or 1 mg i.m . of flunitrazepam ( N=15 ) during an aggressive event . Verbal and physical aggression was measured over time with the Overt Aggression Scale . Patients were also rated with the Brief Psychiatric Rating Scale and the Clinical Global Impression scale . RESULTS Both flunitrazepam and haloperidol exhibited acute antiaggressive activity . This beneficial effect , as assessed by the Overt Aggression Scale , was obtained within 30 minutes . CONCLUSIONS Intramuscular flunitrazepam may serve as a convenient , rapid , safe , and effective adjunct to neuroleptics in reducing aggressive behavior in emergency psychiatric setting 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 Objectives : Psychotic agitation of psychiatric patients is a common manifestation that needs emergent management . Traditionally , parenteral or intramuscular injection of antipsychotics was conducted for treatment of psychotic agitation . Considering that the rapidly absorbed form of risperidone ( risperidone orodispersible tablet ) could be used for the agitated patient , comparison of oral risperidone and intramuscular haloperidol was performed in emergency treatment of psychotic agitation in this study . Methods : 124 patients with psychotic agitation were recruited at the emergency room or inpatient ward . They were r and omly assigned to either the group of oral risperidone or intramuscular haloperidol .  Efficacy of both treatments was measured and compared using the 5-item acute agitation cluster from the Positive and Negative Syndrome Scale-Excited Component ( PANSS-EC ) and the Clinical Global Impression-Severity of Illness Scale ( CGI-S ) . Tolerability and safety were also compared between the two groups . Results : The PANSS-EC and CGI-S scores were significantly decreased over time in both treatment groups without any significant group difference and time by group interaction effect ( F = 459.7 , p < 0.0001 ) . There were no serious adverse events in both groups . Conclusion : For the emergency treatment of psychotic agitation , risperidone orodispersible tablet was as effective and tolerable as intramuscular administration of haloperidol . Therefore , we might choose oral medication instead of intramuscular injection for treatment of patients with acute psychotic agitation OBJECTIVE To compare the long-term efficacy and tolerability of oral quetiapine with those of intramuscular haloperidol . METHOD Patients with DSM-IV-diagnosed schizophrenia or schizoaffective disorder requiring long-term antipsychotic treatment were r and omly assigned to open-label oral quetiapine or intramuscular haloperidol decanoate for 48 weeks . Clinicians were instructed to target dosing at 500 mg/day of quetiapine or 200 mg of haloperidol decanoate every 4 weeks . The Positive and Negative Syndrome Scale was used to assess efficacy ; the Simpson-Angus Scale and the Barnes Akathisia Scale were used to assess safety and tolerability . For statistical analyses , a general linear mixed-model repeated- measures analysis of covariance was used , with change scores for dependent variables computed with the baseline score as covariate . Data were collected from 1998 to 2001 . RESULTS Thirty-five patients were enrolled , but 6 did not participate after being informed of their treatment assignment ; 4 of the 6 withdrawals were assigned to haloperidol decanoate . Mean doses at week 48 were 493 mg/day of quetiapine ( N = 16 ) and 170 mg/28 days of haloperidol decanoate ( N = 9 ) . Survival analysis showed no between-group differences in estimates of the number of patients remaining exacerbation-free over time . Both drugs were efficacious , but quetiapine was significantly better than haloperidol decanoate in controlling negative symptoms ( p < .05 ) . The incidence of extrapyramidal symptoms was low in both groups ; patients receiving quetiapine showed significantly greater improvement in rigidity and akathisia ( p < .05 ) . CONCLUSION Oral quetiapine was as efficacious as intramuscular haloperidol in preventing symptom exacerbation over 48 weeks in patients with schizophrenia or schizoaffective disorder , with fewer extrapyramidal symptoms , especially rigidity and akathisia .  Quetiapine was more efficacious than haloperidol decanoate in treating negative symptoms OBJECTIVES Schizophrenia causes significant impairments of quality of life . As treatment approaches have advanced , more attention has been given to re-integrating patients into their psychosocial environments , rather than simply monitoring psychotic symptoms . The development of the second-generation antipsychotics raised hope that these medications would provide better quality of life improvement than conventional antipsychotics . This improvement is particularly relevant early in the course of schizophrenia . METHODS To address these considerations , improvements in measures of general health and social function ( determined using the SF-36 ) were assessed in 195 patients with first-episode schizophrenia for up to one year following r and omization to either olanzapine or haloperidol  in a double blind clinical trial . We hypothesized that olanzapine would demonstrate better improvement on these measures than haloperidol . In order to test this hypothesis , we used a repeated measure model with SF-36 scores as the outcome , and treatment group , time , time2 , time-by-treatment group interaction , and time2-by-treatment group interaction as fixed effects . RESULTS Both treatments demonstrated similar changes on the SF-36 . Independent of treatment , patients demonstrated significant improvements in most of the SF-36 subscales , which approached normative scores by the end of one year of treatment . Forty-six of 100 olanzapine-treated patients and 37 of 95 haloperidol-treated patients completed the one year of this study ( p<.4 ) . CONCLUSIONS These results suggest an important initial treatment goal for patients with new onset schizophrenic disorders , namely that they can expect to recover significant quality of life and social function at least initially in treatment To examine the quality of life ( QoL ) and clinical outcomes for Asian schizophrenic out patients treated with olanzapine or haloperidol . Patients were r and omized to 24-weeks ' treatment with either olanzapine ( n = 144 ) or haloperidol ( n = 132 ) in a double-blind , prospect i ve , multi-country study . The QLS and WHO-BREF were assessed for QoL ; the PANSS , BPRS and CGI scales for clinical status ; the BAS , AIMS and SAS scales for physical dysfunction . Regardless of antipsychotic , QoL improved significantly at 8 weeks and maintained this improvement at 24 weeks . Compared with haloperidol , olanzapine treatment was associated with significantly better QoL in the WHO-BREF physical and social relationship domains , better improvements in extrapyramidal symptoms in BAS and SAS scores , as well as lower incidence of adverse events . Patients taking haloperidol were more likely to be co-prescribed anticholinergics . The comparatively superior side-effect profile and tolerability of olanzapine may have contributed to enhance domain-specific QoL for these Asian out patients Background : Little information is available on the impact of the atypical antipsychotic olanzapine on quality of life ( QOL ) . A 6-week , double-blind r and omized multicenter trial , with a long-term extension , was conducted to evaluate the clinical efficacy and QOL of olanzapine and haloperidol in treating schizophrenia and other psychotic disorders . Methods : A total of 828 out patients provided QOL data . Study patients were aged greater than 18 years with a DSM-III-R diagnosis of schizophrenia , schizophreniform disorder , or schizoaffective disorder and baseline BPRS ( items scored on 0–6 scale ) total scores , ≥18 were r and omized to 6 weeks of treatment with olanzapine 5 to 20 mg/day or haloperidol 5 to 20 mg/day . Patients entered a 46-week double-blind extension if they demonstrated minimal clinical response and were tolerant to study medication . The Quality of Life Scale ( QLS ) and SF-36 Health Survey were used to evaluate QOL . Results : During the 6-week acute phase , olanzapine treatment significantly improved BPRS total ( p = 0.004 ) , PANSS total scores ( p = 0.043 ) , QLS total ( p = 0.005 ) , intrapsychic foundations ( p < 0.001 ) and interpersonal relations scores ( p = 0.036 ) , and SF-36 mental component summary scores ( p < 0.001 ) compared with haloperidol . During the extension phase , olanzapine treatment significantly improved PANSS negative scores ( p = 0.035 ) and improved QLS total ( p = 0.001 ) , intrapsychic foundations ( p < 0.001 ) , and instrumental role category scores ( p = 0.015 ) versus haloperidol treatment . Significantly more  haloperidol patients discontinued treatment due to adverse events during the acute and extension phases ( p = 0.041 and p = 0.014 , respectively ) . Changes in QLS total and MCS scores were associated with changes in clinical symptoms , depression scores and extrapyramidal symptoms . Conclusions : Olanzapine was more effective than haloperidol in reducing severity of psychopathology and in improving QOL in patients with schizophrenia and other psychotic disorders . The QOL benefits of olanzapine , although modest , may be important for long-term treatment Objective To determine whether haloperidol alone results in swifter and safer tranquillisation and sedation than haloperidol plus promethazine . Design Pragmatic r and omised open trial ( January-July 2004 ) . Setting Psychiatric emergency room , Rio de Janeiro , Brazil . Participants 316 patients who needed urgent intramuscular sedation because of agitation , dangerous behaviour , or both . Interventions Open treatment with intramuscular haloperidol 5 - 10 mg or intramuscular haloperidol 5 - 10 mg plus intramuscular promethazine up to 50 mg ; doses were at the discretion of the prescribing clinician . Main outcome measures The primary outcome was proportion tranquil or asleep by 20 minutes . Secondary outcomes were asleep by 20 minutes ; tranquil or asleep by 40 , 60 , and 120 minutes ; physically restrained or given additional drugs within 2 hours ; severe adverse events ; another episode of agitation or aggression ; additional visit from the doctor during the subsequent 24 hours ; overall antipsychotic load in the first 24 hours ; and still in hospital after 2 weeks . Results Primary outcome data were available for 311 ( 98.4 % ) people , 77 % of whom were thought to have a psychotic illness . Patients allocated haloperidol plus promethazine were more likely to be tranquil or asleep by 20 minutes than those who received intramuscular haloperidol alone ( relative risk 1.30 , 95 % confidence interval 1.10 to 1.55 ; number needed to treat 6 , 95 % confidence interval 4 to 16 ; P=0.002 ) . No differences were found after 20 minutes . However , 10 cases of acute dystonia occurred , all in the haloperidol alone group . Conclusions Haloperidol plus promethazine is a better option than haloperidol alone in terms of speed of onset of action and safety . Enough data are now available to change guidelines that continue to recommend treatments that leave people exposed to longer periods of aggression than necessary and patients vulnerable to distressing and unsafe adverse effects . Trial registration Current Controlled Trials IS RCT N83261243 Introduction Agitation is a major problem in acute schizophrenia . Only a few studies have tested antipsychotic agents in severely agitated patients , mainly because of legal issues . Furthermore , most studies were limited to the first 24 hours . We aim ed to investigate the efficacy of oral haloperidol , risperidone , and olanzapine in reducing psychotic agitation in severely agitated patients with schizophrenia or schizophreniform or schizoaffective disorder over 96 hours using a prospect i ve , r and omized , rater-blinded , controlled design within a naturalistic treatment regimen . Methods In total , 43 severely agitated patients at acute care psychiatric units were enrolled . Participants were r and omly assigned to receive either daily haloperidol 15 mg , olanzapine 20 mg , or risperidone 2 to 6 mg over 5 days . Positive and Negative Syndrome Scale psychotic agitation subscale score was the primary outcome variable . A mixed-model analysis was applied . Results All drugs were effective for rapid tranquilization within 2 hours . Over 5 days , the course differed between agents ( P < 0.001 ) , but none was superior . Dropouts occurred only in the risperidone and olanzapine groups . Men responded better to treatment than did women during the initial 2 hours ( P = 0.046 ) as well as over the 5-day course ( P < 0.001 ) . No difference between drug groups was observed regarding diazepam or biperiden use . Conclusions Oral haloperidol , risperidone , and olanzapine seem to be suitable for treating acute severe psychotic agitation in schizophrenia spectrum disorders . Response to oral antipsychotics demonstrated a gender effect with poorer outcome in women throughout the study OBJECTIVE To compare the effectiveness of intramuscular olanzapine , ziprasidone , haloperidol plus promethazine , haloperidol plus midazolam and haloperidol alone as the first medication(s ) used to treat patients with agitation and aggressive behavior . METHOD One hundred fifty patients with agitation caused by psychotic or bipolar disorder were r and omly assigned under double-blind conditions to receive olanzapine , ziprasidone , haloperidol plus midazolam , haloperidol plus promethazine or haloperidol alone . The Overt Agitation Severity Scale , Overt Aggression Scale and Ramsay Sedation Scale were applied within 12 hours after the first dosage . RESULTS All medications produced a calming effect within one hour of administration , but only olanzapine and haloperidol reduced agitation by less than 10 points , and only olanzapine reduced aggression by less than four points in the first hour . After twelve hours , only patients treated with haloperidol plus midazolam had high levels of agitation and aggression and also more side effects . Ziprasidone , olanzapine and haloperidol alone had more stable results for agitation control , while ziprasidone , haloperidol plus promethazine and olanzapine had stable results for aggression control . CONCLUSION Olanzapine , ziprasidone , haloperidol plus promethazine , haloperidol plus midazolam and haloperidol were effective in controlling agitation and aggression caused by mental illness over 12 hours . Although all the drugs had advantages and disadvantages , haloperidol plus midazolam was associated with the worst results in all the observed parameters Twenty acutely psychotic male psychiatric in patients were assigned to two groups and treated with high- and low-dose haloperidol using a rapid neuroleptization technique . A six-day maintenance phase followed . Both groups improved at one hour , one day , and seven days after starting treatment , and neither group differed as to degree or rapidity of symptom alleviation . Therefore , the results of the study do not give experimental support for the administration of high doses of haloperidol to young , acutely psychotic in patients with relatively good prognoses In a double-blind controlled study , 20 acutely psychotic in patients were treated with different haloperidol dosage regimens . Over a 24-hour period , 10 of the patients were treated with rapid intramuscular neuroleptization at 10 mg per dose and 10 at 2 mg per dose . The patients were then treated for 6 more days with an oral dose equivalent to that given over the first 24 hours of treatment , with doctor 's choice adjustments as needed . Behavioral change was rated using the Brief Psychiatric Rating Scale ( BPRS ) . Blood sample s drawn at baseline and late in the treatment were assayed for plasma and red blood cell haloperidol levels . Although neither of these variables showed a significant correlation with behavioral improvement , the ratio of plasma/RBC haloperidol levels significantly correlated with improvement During a study of neuroleptic threshold haloperidol doses as treatment for newly admitted schizophrenic patients , we examined whether variables extracted from patients ' clinical histories , the type and severity of patients ' psychopathology at baseline , or the emergence of specific extrapyramidal side effects ( EPSE ) during treatment were associated with therapeutic response . Rapid therapeutic response was most powerfully predicted by a short ( less than 1 month ) duration of active illness prior to admission . Severe psychopathology at baseline , or the development of akathisia at neuroleptic threshold doses , portended against early response . More gradual therapeutic response was also associated with limited ( less than 6 months ) duration of active illness prior to admission . Motor retardation at baseline also characterized late responders . Active illness for more than 6 months prior to admission , greater chronicity of overall course , and heavy nicotine consumption characterized nonresponders
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 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 .