Benzodiazepines for psychosis-induced aggression or agitation. Chlorpromazine, clotiapine and thioridazine--a comparative clinical trial on Bantu psychotic patients. Clotiapine compared with chlorpromazine in chronic schizophrenia Reducing violence in severe mental illness: randomised controlled trial of intensive case management compared with standard care Current practices in managing acutely disturbed patients at three hospitals in Rio de Janeiro-Brazil: a prevalence study Predictors of acute dystonia in first-episode psychotic patients. Rapid tranquillisation in psychiatric emergency settings in Brazil: pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients. Randomised controlled trial of day and in-patient psychiatric treatment. 2: Comparison of two hospitals. Initial treatment of severe acute psychosis with fast orally disintegrating risperidone tablets. Alprazolam as a neuroleptic adjunct in the emergency treatment of schizophrenia. Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting. Pragmatic randomised trial of intramuscular lorazepam v. haloperidol plus promethazine. Rapid tranquillisation in psychiatric emergency settings in India: pragmatic randomised controlled trial of intramuscular olanzapine versus intramuscular haloperidol plus promethazine
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 In a non-blind assessment of 3 neuroleptic drugs  , chlorpromazine ( Largactil ) , thioridazine ( Melleril ) and clotiapine ( Etomine ) , we found Etomine to be the drug of choice when the diagnosis is in doubt between a toxic psychosis or schizophrenia . This drug also offered the highest discharge rate , 77'7 % at 12 weeks compared with 73'5 % in the thioridazine group , and 55'5 % in the chlorpromazine group . No clouding of consciousness was seen in the clotiapine group , whereas it was troublesome in the chlorpromazine group in patients having received high parenteral doses OBJECTIVES Clotiapine is a classic neuroleptic with a chemical structure similar to clozapine . It was said that patients unresponsive to other neuroleptics respond to clotiapine although it causes extrapyramidal syndromes ( EPS ) like other typical neuroleptics . We conducted a study of clotiapine vs. chlorpromazine in severe chronic active psychotic hospitalized schizophrenia patients . METHODS The design was double-blind crossover of clotiapine vs chlorpromazine . No washout was necessary from previous neuroleptic treatment , and flexible overlap with the study medication was individualized for each patient . Patients were treated after reaching neuroleptic monotherapy for 3 months with clotiapine and 3 months with chlorpromazine , in r and om order . Medication was supplied in identical capsules of 100 mg chlorpromazine or 40 mg of clotiapine .  Positive and Negative Syndrome Scale ( PANSS ) and Clinical Global Impression ( CGI ) were rated every 2 weeks and Nurse 's Observation Scale for Inpatient Evaluation ( NOSIE ) every month . RESULTS Fifty-eight patients were r and omized . Forty-three patients completed at least one phase of the study , and thirty-three completed both phases . Because of the small number of hostel patients and the very high dropout rate in the hostel patients , data analysis was done separately for in patients and hostel patients . Clotiapine was significantly superior to chlorpromazine in 26 in patients completing the crossover , on the PANSS , NOSIE and CGI .  Clotiapine was also superior to chlorpromazine in an analysis of the parallel inpatient groups in the first three months before the crossover . CONCLUSION Some classic neuroleptic compounds may have superiority to chlorpromazine in a " clozapine-like " manner , despite a typical profile for EPS Abstract Objectives : To establish whether intensive case management reduces violence in patients with psychosis in comparison with st and ard case management . Design : R and omised controlled trial with two year follow up . Setting : Four inner city community mental health services . Participants : 708 patients with established psychotic illness allocated at r and om to intervention ( 353 ) or control ( 355 ) group . Intervention : Intensive case management ( caseload 10–15 per case manager ) for two years compared with st and ard case management ( 30 - 35 per case manager ) . Main outcome measure : Physical assault over two years measured by interviews with patients and case managers and examination of case notes . Results : No significant reduction in violence was found in the intensive case management group compared with the control group ( 22.7 % v 21.9 % , P=0.86 ) . Conclusions : Intensive case management does not reduce the prevalence of violence in psychotic patients in comparison with st and ard care . What is already known on this topic Psychosis and violence are known to be associated Community psychiatric interventions aim ed at reducing the risk of violence have not been evaluated What this study adds Increasing the intensity of contact between patients and case managers does not reduce the prevalence of violent behaviour in patients with psychosis Younger age , learning difficulties , and a history of violence , drug misuse , and victimisation predict violent behaviour in psychotic 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 Sixty-two first-episode psychotic patients who were neuroleptic-naive were studied to examine predictors of acute dystonia after treatment with haloperidol . Twenty-three patients developed dystonia , two of them despite being treated with biperiden . Biperiden significantly prevented dystonic reactions . Dystonia development was significantly related to younger age , severity of illness , and negative symptoms at baseline and showed a trend to be related to positive symptoms as well . No significant effect of gender or diagnosis was found . The authors suggest that young , severely ill patients in their first psychotic episode who have never been treated with neuroleptics might be at higher risk to develop dystonia 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 OBJECTIVE Until recently , conventional antipsychotics were the st and ard pharmacotherapy for psychosis and behavioral disturbances associated with dementia . This double-blind , placebo-controlled study compared the acute efficacy of the selective serotonin reuptake inhibitor citalopram and the neuroleptic perphenazine with placebo for the treatment of psychosis and behavioral disturbances in nondepressed patients with dementia . METHOD Eighty-five hospitalized patients with at least one moderate to severe target symptom ( aggression , agitation , hostility , suspiciousness , hallucinations , or delusions ) were r and omly assigned to receive either citalopram , perphenazine , or placebo under double-blind conditions for up to 17 days . RESULTS Patients treated with citalopram or perphenazine showed statistically significant improvement on several Neurobehavioral Rating Scale factor scores . Compared to those receiving placebo , only patients treated with citalopram showed significantly greater improvement in their total Neurobehavioral Rating Scale score as well as in the scores for the agitation/aggression and lability/tension factors . Side effect scores were similar among the three treatment groups . CONCLUSIONS Citalopram was found to be more efficacious than placebo in the short-term hospital treatment of psychotic symptoms and behavioral disturbances in nondepressed , demented patients Acutely ill patients presenting for admission in two district psychiatric services were r and omly allocated to day-hospital or in-patient care . In both services a quarter of all admissions could not be allocated because they were too ill ( half of these were compulsory admissions ) ; these patients were predominantly manic and schizophrenic patients with pronounced psychotic symptoms and disturbed behaviour . In one service 80 % ( 41/51 ) of patients r and omly allocated to day-hospital treatment were successfully engaged in treatment compared with 54 % ( 19/35 ) in the other service . This difference arose because only patients with mildly disturbed behaviour could be treated at the second day hospital . For patients who were successfully allocated , the outcome of treatment was similar in terms of psychiatric symptoms and social functioning . The results of a treatment trial for acutely ill patients in one district service can not be generalised to other district services without due attention to the factors , such as staffing levels , which determine the degree of disturbed behaviour that can be tolerated in the day hospital INTRODUCTION Although the use of atypical antipsychotics is the st and ard of care in the maintenance treatment of psychosis , most clinicians still rely on conventional neuroleptics to treat acutely agitated psychotic patients . The objective of this study was to evaluate the effectiveness and safety of a fast orally disintegrating tablet formulation of risperidone in the initial treatment of a large sample of very acutely ill psychotic patients . METHODS In this multi-center , prospect i ve , open-label observational trial , 191 schizophrenic patients were treated upon admission to hospital with fast orally disintegrating risperidone tablets for up to seven days . Co-medication was per usual clinical practice and at physician 's discretion . Psychopathology was rated at baseline , 2 , 24 and 48 hours and 4 and 7 days after initiation of therapy . RESULTS A mean PANSS total score of 114.3+/-23.4 at baseline reflected a severely exacerbated patient population . The PANSS total score was significantly reduced to 83.6+/-26.8 ( p<0.0001 ) and the CGI from 5.6+/-0.7 to 4.5+/-1.1 ( p<0.0001 ) after 7 days . The median time to calmness was 70 min and the associated PANSS item 4 ( excitation ) dropped two hours after the first intake of the study medication from 4.3+/-1.5 to 3.1+/-1.5 ( p<0.0001 ) . A total of 172 patients ( 90.1 % ) out of 191 completed the study . The median risperidone dose was 2 mg/d at the initiation of therapy and 4 mg/d after one week . CONCLUSION Oral treatment of acutely exacerbated schizophrenic patients with fast orally disintegrating risperidone tablets , alone or in combination with benzodiazepines , was associated with a rapid onset of action and a significant and clinical ly relevant improvement of acute symptoms OBJECTIVE While neuroleptics remain the mainstay of drug intervention in the emergency management of psychosis , a variety of agents have received study as alternatives or adjuncts to these drugs in an attempt to improve the safety and efficacy of acute treatment . The purpose s of this study were to investigate the efficacy and safety of alprazolam as a neuroleptic adjunct for schizophrenic patients in psychotic relapse and to clarify the effects of combination treatment on specific aspects of the psychotic process . METHOD Twenty-eight acutely psychotic patients with schizophrenia who were admitted to an emergency psychiatric service were r and omly assigned to treatment with either haloperidol and alprazolam or haloperidol with placebo under double-blind conditions . Drug administration lasted 72 hours . RESULTS Both groups improved significantly . The combination-treated group required significantly less medication and had 56 % fewer dystonic reactions . The addition of alprazolam was most effective for symptoms of excitement and uncooperativeness , particularly in the initial hours of treatment . CONCLUSIONS The combination of alprazolam and haloperidol seems to be the most effective for agitated patients , particularly in the first 48 hours of treatment . It may also result in fewer dystonic reactions BACKGROUND The pharmacological management of violence in people with psychiatric disorders is under- research ed . AIMS To compare interventions commonly used for controlling agitation or violence in people with serious psychiatric disorders . METHOD We r and omised 200 people to receive intramuscular lorazepam ( 4 mg ) or intramuscular haloperidol  ( 10 mg ) plus promethazine ( 25 - 50 mg mix ) . RESULTS At blinded assessment s 4 h later ( 99.5 % follow-up ) , equal numbers in both groups ( 96 % ) were tranquil or asleep . However , 76 % given the haloperidol-promethazine mix were asleep compared with 45 % of those allocated lorazepam ( RR=2.29,95 % CI 1.59 - 3.39 ; NNT=3.2,95 % CI 2.3 - 5.4 ) . The haloperidol-promethazine mix produced a faster onset of tranquillisation/sedation and more clinical improvement over the first 2 h. Neither intervention differed significantly in the need for additional intervention or physical restraints , numbers absconding , or adverse effects . CONCLUSIONS Both interventions are effective for controlling violent/agitated behaviour . If speed of sedation is required , the haloperidol-promethazine combination has advantages over lorazepam Objective To compare the effect of intramuscular olanzapine with intramuscular haloperidol plus promethazine on rapid tranquillisation of agitated or violent people with mental illness .  Design Pragmatic , allocation concealed , r and omised controlled trial . Setting Emergency services of a general hospital psychiatry department in Vellore , south India . Participants 300 adults with agitated or violent behaviour as a result of mental illness ; 150 r and omised to intramuscular olanzapine and 150 r and omised to intramuscular haloperidol plus promethazine .  Interventions Open treatment with intramuscular olanzapine or intramuscular haloperidol plus promethazine . Main outcome measures Primary outcome was proportion of patients who were tranquil or asleep at 15 minutes and 240 minutes . Secondary outcomes were proportion of patients who were tranquil , asleep , restrained , absconding , or clinical ly improved at 15 , 30 , 60 , 120 , and 240 minutes ; additional medical interventions and adverse effects over four hours ; and compliance with oral drugs and adverse effects over two weeks . Results Of 300 people r and omised to receive either intramuscular olanzapine or intramuscular haloperidol plus promethazine , follow-up data were available for primary outcomes for 298 ( 99 % ) . Both treatments result ed in similar proportions of people being tranquil or asleep at 15 minutes ( olanzapine 131/150 ( 87 % ) , haloperidol plus promethazine 136/150 ( 91 % ) ; relative risk 0.96 , 95 % confidence interval 0.34 to 1.47 ) and 240 minutes ( olanzapine 144/150 ( 96 % ) , haloperidol plus promethazine 145/150 ( 97 % ) ; relative risk 0.99 , 0.95 to 1.03 ) . However , more people given olanzapine than those given haloperidol plus promethazine required additional drugs over four hours ( 65/150 ( 43 % ) v 31/150 ( 21 % ) ; relative risk 2.07 , 1.43 to 2.97 ) . Adverse effects were uncommon with both treatments . Conclusions Intramuscular olanzapine and intramuscular haloperidol plus promethazine were effective at rapidly tranquillising or sedating agitated or violent  patients with mental illness but the combination result ed in fewer additional medical interventions within four hours of intervention . Trial registration Clinical trials NCT00455234
REVIEW ER 'S CONCLUSIONS We found no significant evidence to support the use of clotiapine rather than other ' st and ard ' or ' non-st and ard ' treatments for the management of  acute psychotic illness .
BACKGROUND Acute psychotic illness , especially when associated with agitated or violent behaviour , requires urgent pharmacological tranquillisation or sedation .
Clotiapine , a dibenzothiazepine neuroleptic , is being used for this purpose in several countries .
OBJECTIVES To estimate the effects of clotiapine when compared to other ' st and ard ' or ' non-st and ard ' treatments of acute psychotic illness in controlling disturbed behaviour and reducing psychotic symptoms .