title: Intramuscular flunitrazepam versus intramuscular haloperidol in the emergency treatment of aggressive psychotic behavior. A quantifiable, Brief Mental Status Examination for emergency patients. Does psychomotor agitation in major depressive episodes indicate bipolarity? A Naturalistic Study of Intramuscular Haloperidol Versus Intramuscular Olanzapine for the Management of Acute Agitation Quetiapine Versus Placebo in Combination With Lithium or Divalproex for the Treatment of Bipolar Mania Use of antipsychotics and benzodiazepines in patients with psychiatric emergencies: Results of an observational trial Demographics, clinical characteristics, and treatment of aggressive patients admitted to the acute behavioral unit of a community general hospital: a prospective observational study. Comparison of risperidone oral solution and intramuscular haloperidol with the latter shifting to oral therapy for the treatment of acute agitation in patients with schizophrenia Are Low Doses of Antipsychotics Effective in the Management of Psychomotor Agitation? A Randomized, Rated-Blind Trial of 4 Intramuscular Interventions Psychomotor agitation in major depressive disorder is a predictive factor of mood-switching. Quetiapine with lithium or divalproex for the treatment of bipolar mania: a randomized, double-blind, placebo-controlled study. A randomized, double-blind, placebo-controlled efficacy and safety study of quetiapine or lithium as monotherapy for mania in bipolar disorder. Randomized controlled trial of intramuscular droperidol versus midazolam for violence and acute behavioral disturbance: the DORM study. Comparison of Risperidone Orodispersible Tablet and Intramuscular Haloperidol in the Treatment of Acute Psychotic Agitation: A Randomized Open, Prospective Study Early onset of antipsychotic response in the treatment of acutely agitated patients with psychotic disorders A randomized, double-blind, placebo-controlled study of rapid-acting intramuscular olanzapine in Japanese patients for schizophrenia with acute agitation Rapid acute treatment of agitation in individuals with schizophrenia: multicentre, randomised, placebo-controlled study of inhaled loxapine. TREC-Rio trial: a randomised controlled trial for rapid tranquillisation for agitated patients in emergency psychiatric rooms [ISRCTN44153243] Cluster-randomized controlled trial of reducing seclusion and restraint in secured care of men with schizophrenia. Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study. Mood stabilisers plus risperidone or placebo in the treatment of acute mania. International, double-blind, randomised controlled trial. Suicide in a large population of former psychiatric inpatients. Chemical restraint for the agitated patient in the emergency department: lorazepam versus droperidol. Comparison of Intramuscular Olanzapine, Orally Disintegrating Olanzapine Tablets, Oral Risperidone Solution, and Intramuscular Haloperidol in the Management of Acute Agitation in an Acute Care Psychiatric Ward in Taiwan Intramuscular Ziprasidone Versus Haloperidol for Managing Agitation in Chinese Patients With Schizophrenia Predicting community violence from patients discharged from mental health services. The expert consensus guideline series. Treatment of dementia and its behavioral disturbances. Introduction: methods, commentary, and summary. Intramuscular aripiprazole for the treatment of acute agitation in patients with schizophrenia or schizoaffective disorder: a double-blind, placebo-controlled comparison with intramuscular haloperidol High Potency Neuroleptics and Violence in Schizophrenics Rapid tranquilization for agitated patients in emergency psychiatric rooms: a randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone. Management of acute undifferentiated agitation in the emergency department: a randomized double-blind trial of droperidol, ziprasidone, and midazolam. Efficacy and safety of intramuscular aripiprazole in patients with acute agitation: a randomized, double-blind, placebo-controlled trial. A randomized, double-blind, placebo-controlled, study of the efficacy and safety of aripiprazole 10, 15 or 20 mg/day for the treatment of patients with acute exacerbations of schizophrenia. 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Droperidol vs. haloperidol in the initial management of acutely agitated patients. A naturalistic comparison study of the efficacy and safety of intramuscular olanzapine, intramuscular haloperidol, and intramuscular levomepromazine in acute agitated patients with schizophrenia. Effect of nicotine replacement therapy on agitation in smokers with schizophrenia: a double-blind, randomized, placebo-controlled study.
abstract: 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 Although paramedics and emergency department ( ED ) personnel are routinely required to assess the mental states of patients they are attempting to treat , no structured and easily administered tool has been vali date d for their use . The objective of this study was to determine whether a quantitative Brief Mental Status Examination ( BMSE ) can serve as such a tool . The six-item BMSE was administered to 100 ED patients for whom an assessment of mental status was warranted . The st and ard assessment of mental status ( normal , mildly impaired , or severely impaired ) and competence to refuse emergency care were provided by the attending physician . The usefulness and ease of administration of the BMSE were rated by the physicians and nurses administering it . We found that BMSE scores correlated significantly with physicians ' assessment s of patients ' mental status and competence to refuse care . Using physician assessment as a st and ard , the BMSE had a sensitivity of 72 % and a specificity of 95 % in identifying severely impaired individuals . Examiners ' ratings of ease of administration were closely related to the degree of impairment found . Finally , examiners rated the BMSE as useful in 98 % of cases . We conclude from these preliminary results that the BMSE , upon further testing , may prove to be a valid and useful tool for assessing the mental states of emergency patients in both prehospital and ED setting Abstract Background Kraepelin ’s partial interpretation of agitated depression  as a mixed state of “ manic-depressive insanity ” ( including the current concept of bipolar disorder ) has recently been the focus of much research . This paper tested whether , how , and to what extent both psychomotor symptoms , agitation and retardation in depression are related to bipolarity and anxiety . Method The prospect i ve Zurich Study assessed psychiatric and somatic syndromes in a community sample of young adults ( N = 591 ) ( aged 20 at first interview ) by six interviews over 20 years ( 1979–1999 ) .  Psychomotor symptoms of agitation and retardation were assessed by professional interviewers from age 22 to 40 ( five interviews ) on the basis of the observed and reported behaviour within the interview section on depression . Psychiatric diagnoses were strictly operationalised and , in the case of bipolar-II disorder , were broader than proposed by DSM-IV-TR and ICD-10 . As indicators of bipolarity , the association with bipolar disorder , a family history of mania/hypomania/cyclothymia , together with hypomanic and cyclothymic temperament as assessed by the general  behavior inventory  ( GBI ) [ 15 ] , and mood lability ( an element of cyclothymic temperament ) were used . Results Agitated and retarded depressive states were equally associated with the indicators of bipolarity and with anxiety . Longitudinally , agitation and retardation were significantly associated with each other ( OR = 1.8 , 95 % CI = 1.0–3.2 ) , and this combined group of major depressives showed stronger associations with bipolarity , with both hypomanic/cyclothymic and depressive temperamental traits , and with anxiety . Among agitated , non-retarded depressives , unipolar mood disorder was even twice as common as bipolar mood disorder . Conclusion Combined agitated and retarded major depressive states are more often bipolar than unipolar , but , in general , agitated depression ( with or without retardation ) is not more frequently bipolar than retarded depression ( with or without agitation ) , and pure agitated depression is even much less frequently bipolar than unipolar . The findings do not support the hypothesis that agitated depressive syndromes are mixed states . Limitations The results are limited to a population up to the age of 40 ; bipolar-I disorders could not be analysed ( small N ) Objective Published research on agitation is limited by the difficulty in generalizing findings from trials using moderately agitated , carefully selected patients treated with single agents . More specifically , there are few comparative studies examining common intramuscular ( IM ) regimens ( ie , haloperidol with or without benzodiazepines ) with IM atypical antipsychotics . Therefore , we conducted a retrospective chart review to compare IM olanzapine and haloperidol in a “ real-world ” population with agitation . Method We performed a retrospective evaluation of charts from 146 consecutive emergency department patients who received either IM haloperidol or IM olanzapine for agitation . We used a clinical ly oriented proxy marker of efficacy — the necessity for additional medication intervention for agitation (AMI)—as our primary outcome measure . Results Additional medication intervention for agitation was required by 43 % ( 13/30 ) patients when haloperidol was given alone and by 18 % ( 13/72 ) when haloperidol was given with a benzodiazepine . In the case of olanzapine , AMI was required by 29 % ( 6/21 ) of patients receiving olanzapine alone and by 18 % ( 2/11 ) of patients given olanzapine plus a benzodiazepine . A significant percentage of patients had clinical characteristics ( nonpsychiatric triage complaint , drug/alcohol use , severe agitation ) that differ from more selective sample s. Conclusions Overall , these finding suggest that in a naturalistic emergency department setting , haloperidol monotherapy is less effective — at least in requiring AMI — than olanzapine with or without a benzodiazepine or haloperidol plus a benzodiazepine . Moreover , these later 3 regimens seemed comparable . Prospect i ve studies examining the treatment of real-world agitation , including head-to-head comparisons of the haloperidol-benzodiazepine combination with newer IM antipsychotics , are needed Abstract : Quetiapine ( QTP ) combined with lithium ( Li ) or divalproex ( DVP ) for the treatment of mania was evaluated in 2 double-blind , placebo-controlled studies . Patients were r and omized to 3 or 6 weeks of treatment with QTP plus Li/DVP or placebo ( PBO ) plus Li/DVP . Quetiapine was dosed up to 800 mg/d ; Li was dosed to achieve serum concentrations of 0.7 - 1.0 mEq/L and DVP to 50 - 100 μg/mL. A total of 402 patients were r and omized : 197 to QTP + Li/DVP and 205 to PBO + Li/DVP . The mean quetiapine dose in responders was 492 ( ±204 ) mg/d . Improvement in the Young Mania Rating Scale ( YMRS ) at day 21 in the QTP + Li/DVP group ( −15.29 ) was statistically superior to the PBO + Li/DVP group ( −12.19 ) ( P < 0.05 ) . A statistically significant difference in favor of quetiapine was observed within the first week ( P < 0.05 ) . Significantly more QTP + Li/DVP patients achieved a response ( ≥50 % decrease in the YMRS ) at day 21 ( QTP + Li/DVP , 55.7 % ; PBO + Li/DVP , 41.6%;P < 0.01 ) . Improvements in Clinical Global Impression-Bipolar Severity of Illness scores by day 21 were also significantly greater in QTP + Li/DVP-treated patients ( −1.59 ) versus PBO + Li/DVP ( −1.19 ) ( P < 0.01 ) . Common adverse events ( ≥5 % and twice that in the PBO + Li/DVP group ) in the QTP + Li/DVP group were somnolence , dry mouth , and asthenia . Quetiapine combined with Li/DVP was not associated with extrapyramidal symptoms ( including akathisia ) or emergent depression . More QTP + Li/DVP-treated patients completed the trial , and there was no difference in discontinuation rates due to adverse events between the two groups . Quetiapine , in combination with lithium or divalproex , is well tolerated and has superior efficacy to lithium or divalproex alone in the treatment of bipolar mania 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 OBJECTIVE Aggressive patients are not uncommon in acute inpatient behavioral health units of general hospitals . Prior research identifies various predictors associated with aggressive inpatient behavior . This prospect i ve observational study examines the demographic and clinical characteristics of aggressive in patients and the routine medications these patients were receiving at discharge . METHOD Thirty-six adults diagnosed with a DSM-IV mental disorder who met 2 of 6 established inclusion criteria for high violence risk and a Clinical Global Impressions-Severity of Illness ( CGI-S ) scale score ≥ 4 were observed for a maximum of 28 days on the 23-bed case mix acute behavioral health unit of St Luke 's University Hospital , Bethlehem , Pennsylvania , from January 2012 to May 2013 . Primary outcome measures were the Modified Overt Aggression Scale ( MOAS ) and CGI-S ; secondary measures were symptom outcome measures and demographic and clinical characteristics data . Analysis was conducted using repeated measures methodology . RESULTS Younger males with a history of previous violence , psychiatric admissions , and symptoms of severe agitation were more at risk for aggressive behavior . Positive psychotic symptoms , a diagnosis of bipolar disorder , substance use , and comorbid personality disorders also increased risk . Significant improvements from baseline to last visit were observed for the CGI-S and MOAS ( P < .001 for both ) , with a significant correlation between the MOAS and CGI-S at last visit ( P < .001 ) . Only the symptom of agitation was significantly correlated to MOAS scores at both baseline and last visit ( P < .001 ) . CONCLUSION Patients significantly improved over time in both severity of illness and level of aggression This r and omized , parallel-group , open study investigated the efficacy and safety of risperidone oral solution ( RIS-OS ) in combination with clonazepam and intramuscular haloperidol for the treatment of acute agitation in patients with schizophrenia , and the study explored the possibility of decreasing the efficacy of an acute 6-week treatment by switching intramuscular haloperidol injection to RIS-OS .  Two hundred and five agitation-exhibiting schizophrenic in patients at six hospitals were originally included in the study . The 47-day trial consisted of 5 days ( session I ) of receiving either oral treatment ( RIS-OS plus clonazepam ) or intramuscular treatment ( intramuscular haloperidol ) and a 42-day ( session II ) period of either withdrawing from clonazepam or shifting from intramuscular haloperidol to a RIS-OS period . The primary efficacy outcome was measured as the change in the Positive and Negative Syndrome Scale-Excited Component ( PANSS-EC ) in session I and the change in the PANSS in session II . Safety was assessed by the frequency of the adverse events . Mean PANSS-EC improvement was significant after 5 days of treatment in both groups ( P>0.05 ) and was similar between the two treatment groups ( P<0.01 ) . Most patients ’ PANSS-EC scores improved or remained stable during the drawback/shift treatment period . Efficacy was not significantly different between the two treatment groups after the 6-week treatment ( P>0.05 ) . However , combination treatment exhibited greater efficacy , and adverse events , especially extrapyramidal symptoms , were lower with the oral treatment than with the intramuscular treatment in session I. These results show that RIS-OS in combination with clonazepam is an effective treatment , comparable with intramuscular haloperidol , and is well-tolerated for acute agitation in patients with schizophrenia Background Psychomotor agitation can be associated with a wide range of medical conditions . Although clinical practice advocates the use of several drugs for the management of psychomotor agitation , there are still very few controlled studies comparing the profiles of action and the adverse effects of different drugs that induce tranquilization . Objectives The purpose of this study was to compare the efficacy and safety of 4 low-dose pharmacological interventions used to control psychomotor agitation guided by the clinical response . Methods Using a r and omized , rated-blind design , 100 agitated patients were assigned to receive 1 of 4 treatments : haloperidol ( 2.5 mg ) + promethazine ( 25 mg ) ( HLP + PMZ ) , haloperidol ( 2.5 mg ) + midazolam ( 7.5 mg ) ( HLP + MID ) , ziprasidone ( 10 mg ) ( ZIP ) , or olanzapine ( 10 mg ) ( OLP ) . Patients were evaluated just before the intervention and after 30 , 60 , and 90 minutes , using the Agitation-Calmness Evaluating Scale . Adverse effects were assessed within 24 hours after the intervention , using selected items from the UKU Scale ( Ugvalg Klinisk Undersgelser Side Effect Scale ) . According to the clinical indication , medication could be repeated twice after the first injection . Data were analyzed using general linear model with repeated measures and logistic regression . Results All treatment options promoted a reduction in agitation , without causing excessive sedation , although a lower reduction in agitation was observed with HLP + PMZ and ZIP compared with HLP + MID and OLZ . The need for an additional dose of medication was observed in 22 patients , and only 8 remained agitated during the entire 90-minute period . A higher risk for the development of extrapyramidal symptoms within the following 24 hours was observed with HLP + PMZ . Discussion Low doses of haloperidol combined with midazolam can be as effective as olanzapine in reducing psychomotor agitation without increasing the risk of extrapyramidal effects . Because of the higher risk for the occurrence of extrapyramidal symptoms , the combination of haloperidol with promethazine should be considered a second-line treatment option BACKGROUND The relationship between psychomotor agitation in unipolar depression and mood-switching from depression to manic , hypomanic and mixed states has been controversial . We investigated the future risk of initial mood-switching as a function of psychomotor agitation in unipolar depression . METHODS We identified 189 participants diagnosed with major depressive disorder ( MDD ) . We divided all patients with MDD into two categories ( 1 ) agitated patients ( n=74 ) , and ( 2 ) non-agitated patients ( n=115 ) . These groups were prospect ively followed and compared by time to mood-switching . Kaplan-Meier survival curves , log-rank test for trend for survivor functions , and Cox proportional hazard ratio estimates for a multivariate model were conducted to examine the risk of mood-switching by psychomotor agitation . RESULTS During follow-up , mood-switching occurred in 20.3 % of the agitated patients and 7.0 % of the non-agitated patients . In the Kaplan-Meier survival estimates for time to incidence of mood-switching with agitated or non-agitated patients , the cumulative probability of developing mood-switching for agitated patients was higher than those for non-agitated patients ( log-rank test : χ(2)=7.148 , df=1 , p=0.008 ) . Survival analysis was also performed using Cox proportional hazards regression within a multivariate model . The agitation remained significantly associated with incidence of mood-switching ( HR=2.98 , 95 % CI : 1.18 - 7.51 ) . LIMITATIONS We did not make a clear distinction between antidepressant-induced mood-switching and spontaneous switching . CONCLUSIONS The main finding demonstrated that MDD patients with agitation were nearly threefold as likely to experience mood-switching , suggesting that psychomotor agitation in MDD may be related to an indicator of bipolarity OBJECTIVE Evaluate the efficacy and tolerability of quetiapine ( QTP ) combined with lithium ( Li ) or divalproex ( DVP ) in the treatment of acute mania . METHODS Patients were r and omized to 21 days of double-blind treatment with QTP plus Li/DVP , or placebo ( PBO ) plus Li/DVP . QTP was rapidly dosed up to a maximum of 800 mg/day ; Li was dosed to 0.7 - 1.0 mEq/L ; or DVP to 50 - 100 microg/mL. RESULTS Fifty-six of 91 ( 61.5 % ) individuals in the  QTP + Li/DVP group compared with 49 of 100 ( 49 % ) taking PBO + Li/DVP  completed the study . A significantly greater mean reduction in total Young Mania Rating Scale ( YMRS ) score was observed at end-point in patients receiving QTP + Li/DVP compared with those in the PBO + Li/DVP group ( -13.76 versus -9.93 ; p = 0.021 ) . The response rate ( > or = 50 % YMRS improvement ) was significantly higher in the QTP + Li/DVP group than in PBO + Li/DVP-treated patients ( 54.3 % versus 32.6 % ; p = 0.005 ) , as was the proportion of patients achieving clinical remission ( YMRS < 12 ) ( 45.7 % versus 25.8 % ; p = 0.007 ) . Patients receiving QTP + Li/DVP also had a significantly greater improvement in Clinical Global Impressions-Bipolar ( CGI-BP ) Severity of Illness scores ( -1.38 versus -0.78 ; p = 0.001 ) . The mean last-week dose of QTP was 584 mg/day in patients meeting response criteria . Common adverse events ( at least 10 % and twice the rate of Li/DVP ) in the QTP + Li/DVP group included somnolence , dry mouth , asthenia , and postural hypotension . CONCLUSIONS Quetiapine combined with either Li or DVP has superior efficacy compared with Li or DVP monotherapy for treating patients with bipolar mania . Combination therapy was well-tolerated and most adverse events were mild , withdrawal because of adverse events being only 5 % compared with 6 % on Li or DVP monotherapy OBJECTIVE To evaluate the efficacy and tolerability of quetiapine monotherapy versus placebo for the treatment of mania associated with bipolar disorder . METHOD In an international , multicenter , double-blind , parallel-group , 12-week study , patients with a DSM-IV diagnosis of bipolar I disorder ( manic episode ) were r and omly assigned to treatment with quetiapine ( flexibly dosed up to 800 mg/day ) , placebo , or lithium . The primary efficacy measure was change from baseline in Young Mania Rating Scale ( YMRS ) score at day 21 . Data were gathered from April 2001 to May 2002 . RESULTS More patients in the quetiapine ( 72/107 ) and lithium ( 67/98 ) groups completed the study compared with the placebo group ( 35/97 ) . Improvement ( reduction ) in YMRS score was significantly greater for quetiapine than placebo at day 7 ( -8.03 vs. -4.89 ; p < .01 ) , and the difference between groups continued to increase over time to day 21 ( -14.6 vs. -6.7 ; p < .001 ) and to endpoint at day 84 ( -20.3 vs. -9.0 ; p < .001 ) . Significantly more quetiapine patients compared with placebo patients fulfilled YMRS response criteria at day 21 ( 53.3 % vs. 27.4 % ; p < .001 ) and at day 84 ( 72.0 % vs. 41.1 % ; p < .001 ) . Quetiapine was also superior to placebo in efficacy at day 21 and day 84 by all secondary measures . Lithium-treated patients improved significantly compared with placebo patients and similarly to quetiapine-treated patients on the primary efficacy measure . The most common adverse events for quetiapine were dry mouth , somnolence , and weight gain , while lithium was associated with tremor and insomnia . The quetiapine and placebo groups had similar , low levels of extrapyramidal symptom-related adverse events . CONCLUSIONS Quetiapine demonstrated superior efficacy to placebo in patients with bipolar mania and was well tolerated STUDY OBJECTIVE We determine whether droperidol , midazolam , or the combination is more effective for intramuscular sedation in violent and acute behavioral disturbance in the emergency department ( ED ) . METHODS We conducted a blinded r and omized controlled trial of intramuscular sedation for violent and acute behavioral disturbance , comparing droperidol ( 10 mg ) , midazolam ( 10 mg ) , and droperidol ( 5 mg)/midazolam ( 5 mg ) . Inclusion criteria were patients requiring physical restraint and parenteral sedation . The primary outcome was the duration of the violent and acute behavioral disturbance , defined as the time security staff were required . Secondary outcomes included time until additional sedation was administered , staff and patient injuries , further episodes of violent and acute behavioral disturbance , and drug-related adverse effects . RESULTS From 223 ED patients with violent and acute behavioral disturbance , 91 patients were included ; 33 received droperidol , 29 received midazolam , and 29 received the combination . There was no difference in the median duration of the violent and acute behavioral disturbance : 20 minutes ( interquartile range [ IQR ] 11 to 37 min ) for droperidol , 24 minutes ( IQR 13 to 35 minutes ) for midazolam , and 25 minutes ( IQR 15 to 38 minutes ) for the combination . Additional sedation was required in 11 ( 33 % ; 95 % confidence interval [ CI ] 19 % to 52 % ) droperidol patients , 18 ( 62 % ; 95 % CI 42 % to 79 % ) midazolam patients , and 12 ( 41 % ; 95 % CI 24 % to 61 % ) in the combination group . The hazard ratio for additional sedation in the midazolam versus droperidol group was 2.31 ( 95 % credible interval 1.01 to 4.71 ) ; for the combination versus droperidol , 1.18 ( 95 % credible interval 0.46 to 2.50 ) . Patient and staff injuries and number of further episodes of violent and acute behavioral disturbance did not differ between groups . There were two adverse effects for droperidol ( 6 % ; 95 % CI 1 % to 22 % ) , 8 for midazolam ( 28 % ; 95 % CI 13 % to 47 % ) , and 2 for the combination ( 7 % ; 95 % CI 1 % to 24 % ) . An abnormal QT occurred in 2 of 31 ( 6 % ; 95 % CI 1 % to 23 % ) droperidol patients , which was not different from the other groups . CONCLUSION Intramuscular droperidol and midazolam result ed in a similar duration of violent and acute behavioral disturbance , but more additional sedation was required with midazolam . Midazolam caused more adverse effects because of oversedation , and there was no evidence of QT prolongation associated with droperidol compared with midazolam 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 While the efficacy of antipsychotic medications for the treatment of psychosis is generally established , the speed of onset of antipsychotic action remains controversial . The objective of this study was to evaluate the early response ( within the first 24 h ) in psychosis with ziprasidone IM treatment , and to determine whether this early effect is distinct from a reduction in agitation symptoms . METHODS In a 24-h , double-blind study , hospitalized patients with psychotic disorder and acute agitation were r and omized to treatment with fixed doses of IM ziprasidone : 2 mg ( N=38 ) or 20 mg ( N=41 ) . Efficacy assessment s were based on the PANSS positive subscale and PANSS early psychosis factor score ( conceptual disorganization , hallucinatory behavior , and unusual thought content ) at 4 and 24 h. RESULTS Ziprasidone IM demonstrated a significant dose-related effect ( 20 mg vs. 2 mg ) on both the PANSS early psychosis factor score and the PANSS positive subscale at the first post-baseline time point ( 4 h ) , and at 24 h ( all p<0.05 ) . There was a significant direct effect of ziprasidone IM on early psychosis at 24 h ( p<0.05 ) , distinct from improvement in agitation symptoms . CONCLUSIONS These findings suggest , in addition to an early reduction in acute agitation , ziprasidone IM may be associated with a more rapid improvement in psychotic symptoms than previously reported , thus lending further support to the emergent hypothesis of early psychosis improvement in antipsychotic treatment Background Olanzapine rapid-acting intramuscular ( IM ) injection is an atypical antipsychotic drug already used overseas and recently approved in Japan . The objective of this study was to confirm the efficacy of rapid-acting IM olanzapine 10 mg was greater than IM placebo in patients with exacerbation of schizophrenia with acute psychotic agitation by comparing changes from baseline to 2 hours after the first IM injection , as measured by the Positive and Negative Syndrome Scale-Excited Component ( PANSS-EC ) total score . Methods We conducted a placebo-controlled , r and omized , double-blind , parallel-group study in Japanese patients diagnosed with schizophrenia according to the diagnostic criteria specified in the DSM-IV-TR . Patients were r and omized to 2 treatment groups : IM olanzapine ( 10 mg ) or IM placebo . The primary efficacy outcome was the change in PANSS-EC from baseline to 2 hours after the first IM injection . Treatment groups were compared with an analysis of variance model which included treatment and site as factors . During the 24-hour treatment period , safety was assessed by clinical examination and laboratory investigations , electrocardiograms , extrapyramidal symptoms scales , and recording spontaneously reported adverse events . Results Of the 91 r and omized patients , 90 patients ( 45 IM olanzapine-group ; 45 IM placebo-group ) were in the full analysis set . The mean change of PANSS-EC total score from baseline to 2 hours after the first IM injection ( mean±st and ard deviation ) was −9.2±4.5 for the IM olanzapine group and −2.8±5.6 for the IM placebo group . The difference between treatment groups was statistically significant ( p<.001 ) . There were no deaths , serious adverse events , treatment-emergent adverse events ( TEAEs ) leading to discontinuation , severe TEAEs , or instances of oversedation in this study . There were no statistically significant differences between treatment groups in the proportion of patients with potentially clinical ly significant changes in laboratory tests , vital signs ( blood pressure and pulse rate ) , electrocardiograms , and treatment-emergent extrapyramidal symptoms . Conclusion The efficacy of IM olanzapine 10 mg in patients with exacerbation of schizophrenia with acute psychotic agitation was greater than IM placebo in the primary efficacy measure , PANSS-EC . Intramuscular olanzapine 10 mg was shown to be generally safe and tolerable , and could be a new option for treatment of schizophrenia in Japan . Trial Registration BACKGROUND There is a need for a rapid-acting , non-injection , acute treatment for agitation . AIMS To evaluate inhaled loxapine for acute treatment of agitation in schizophrenia . METHOD This phase III , r and omised , double-blind , placebo-controlled , parallel-group study ( Clinical Trials.gov number NCT00628589 ) enrolled 344 individuals who received one , two or three doses of inhaled loxapine ( 5 or 10 mg ) or a placebo . Lorazepam rescue was permitted after dose two . The primary efficacy end-point was change from baseline in Positive and Negative Syndrome Scale-Excited Component ( PANSS-EC ) 2 h after dose one . The key secondary end-point was Clinical Global Impression-Improvement scale ( CGI-I ) score 2 h after dose one . RESULTS Inhaled loxapine ( 5 and 10 mg ) significantly reduced agitation compared with placebo as assessed by primary and key secondary end-points . Reduced PANSS-EC score was evident 10 min after dose one with both 5 and 10 mg doses . Inhaled loxapine was well tolerated , and the most common adverse events were known effects of loxapine or minor oral effects common with inhaled medications . CONCLUSIONS Inhaled loxapine provided a rapid , well-tolerated acute treatment for agitation in people with schizophrenia Background Agitated or violent patients constitute 10 % of all emergency psychiatric treatment . Management guidelines , the preferred treatment of clinicians and clinical practice all differ . Systematic review s show that all relevant studies are small and none are likely to have adequate power to show true differences between treatments . Worldwide , current treatment is not based on evidence from r and omised trials . In Brazil , the combination haloperidol-promethazine is frequently used , but no studies involving this mix exist . Methods TREC-Rio ( Tranquilização Rápida-Ensaio Clínico [ Translation : Rapid Tranquillisation- Clinical Trial ] ) will compare midazolam with haloperidol-promethazine mix for treatment of agitated patients in emergency psychiatric rooms of Rio de Janeiro , Brazil . TREC-Rio is a r and omised , controlled , pragmatic and open study . Primary measure of outcome is tranquillisation at 20 minutes but effects on other measures of morbidity will also be assessed . TREC-Rio will involve the collaboration of as many health care professionals based in four psychiatric emergency rooms of Rio as possible . Because the design of this trial does not substantially complicate clinical management , and in several aspects simplifies it , the study can be large , and treatments used in everyday practice can be evaluated OBJECTIVE This r and omized controlled trial studied whether seclusion and restraint could be prevented in the psychiatric care of persons with schizophrenia without an increase of violence . METHODS Over the course of a year , 13 wards of a secured national psychiatric hospital in Finl and received information about seclusion and restraint prevention . Four high-security wards ( N=88 beds ) for men with psychotic illness were then stratified by coercion rates and r and omly assigned to two equal groups . In the intervention wards , staff , patients , and doctors were trained for six months in applying six core strategies to prevent seclusion-restraint ; six months of supervised intervention followed . Poisson 's regression analyses compared monthly incidence rate ratios ( IRRs ) of coercion and violence ( per 100 patient-days ) . RESULTS The proportion of patient-days with seclusion , restraint , or room observation declined from 30 % to 15 % for intervention wards ( IRR=.88 , 95 % confidence interval [CI]=.86-.90 , p<.001 ) versus from 25 % to 19 % for control wards ( IRR=.97 , CI=.93 - 1.01 , p=.056 ) .  Seclusion-restraint time decreased from 110 to 56 hours per 100 patient-days for intervention wards ( IRR=.85 , CI=.78-.92 , p<.001 ) but increased from 133 to 150 hours for control wards ( IRR=1.09 , CI=.94 - 1.25 , p=.24 ) . Incidence of violence decreased from 1.1 % to .4 % for the intervention wards and from .1 % to .0 % for control wards . Between-groups differences were significant for  seclusion-restraint-observation days ( p=.001 ) and  seclusion-restraint time ( p=.001 ) but not for violence ( p=.91 ) . CONCLUSIONS Seclusion and restraint were prevented without an increase of violence in wards for men with schizophrenia and violent behavior . A similar reduction may also be feasible under less extreme circumstances Rapid tranquilization is a routinely practice d method of calming agitated psychotic patients by use of neuroleptics , benzodiazepines , or both in combination . Although several studies have examined the efficacy of the three approaches , none have compared these treatments in a prospect i ve , r and omized , double-blind , multicenter trial . Ninety-eight psychotic , agitated , and aggressive patients ( 73 men and 25 women ) were prospect ively enrolled during an 18-month period in emergency departments in five university or general hospitals . Patients were r and omly assigned to receive intramuscular injections of lorazepam ( 2 mg ) , haloperidol ( 5 mg ) , or both in combination . Patients in each treatment group received 1 to 6 injections of the same study drug within 12 hours , based on clinical need . They were evaluated hourly after the first injection until at least 12 hours after the last . Efficacy was assessed on the Agitated Behavior Scale ( ABS ) , a modified Brief Psychiatric Rating Scale ( MBPRS ) , Clinical Global impressions ( CGI ) scale , and an Alertness Scale . Effective symptom reduction was achieved in each treatment group with significant ( P < .01 ) mean decreases from baseline at every hourly ABS evaluation . Significant ( P < .05 ) mean differences on the ABS ( hour 1 ) and MBPRS ( hours 2 and 3 ) suggest that tranquilization was most rapid in patients receiving the combination treatment . Study event incidence ( side effects ) did not differ significantly between treatment groups , although patients receiving haloperidol alone tended to have more extrapyramidal system symptoms . The superior results produced by the combination treatment support the use of lorazepam plus haloperidol as the treatment of choice for acute psychotic agitation BACKGROUND Few double-blind trials have examined the efficacy of a combination of a mood stabiliser and an atypical antipsychotic  in acute mania . AIMS To determine the efficacy of risperidone in combination with a mood stabiliser in acute mania . METHOD Patients taking a mood stabiliser were r and omised to 3 weeks ' treatment with risperidone ( n=75 ) or placebo ( n=76 ) . RESULTS Young Mania Rating Scale ( YMRS ) scores improved rapidly with significantly greater reductions at week 1 in the risperidone group compared with the placebo group . At end-point YMRS scores decreased by 14.5 and 10.3 points in the risperidone and placebo groups , respectively . Significant improvements v. placebo ( P<0.05 ) were noted in the risperidone group on several other clinical ly meaningful measures . Additionally , a post hoc analysis excluding carbamazepine-treated patients ( plasma concentrations of risperidone active moiety were 40 % lower in this group ) revealed significantly greater reductions ( P=0.047 ) in YMRS scores in the risperidone group than in the placebo group . Incidence of adverse events was similar in both groups . CONCLUSIONS Risperidone is superior to placebo when used in combination with lithium or divalproex in acute mania AIMS The aim of this study was to identify predictors of completed suicide in a wide sample of psychiatric in patients receiving retrospective and prospect i ve DSM-IV diagnoses . METHODS We followed up 4441 severe psychiatric patients who were hospitalized for some time during a 35-year period in a private hospital setting . We collected sociodemographic , clinical and temperamental data . RESULTS Ninety-six patients from the sample committed suicide .  There were no sex differences in suicide completion and no differences between major psychiatric disorders , but people who had been hospitalized for anxiety disorders did not commit suicide and people with bipolar disorders were more likely to commit suicide than people with unipolar major depression . Shorter-term treatment with lithium and anticonvulsants , longer-term treatment with antidepressants , history of suicide attempts , suicidal thinking , and single status positively predicted completed suicide . Suicide tended to occur after a mean period of about 14 years of duration of disease . Patients ' symptoms during the period preceding suicide were assessed through interviewing patients ' physicians or family members . Symptoms occurring in > 10 % of cases were , in decreasing order , inner tension , racing/crowded thoughts , aggressive behavior , guilt , psychomotor agitation , persecutory ideation , anxiety , and hallucinations . Surprisingly , cyclothymic temperament was less associated with completed suicide as compared to other temperaments . CONCLUSIONS Suicide is likely to occur in a milieu of agitation , mixed anxiety and depression , and psychosis . Longer-term mood stabilizer treatment may reduce the rate of completed suicide Patients presenting to the emergency department with acute agitation frequently require physical and chemical restraint . To determine the efficacy of lorazepam vs. droperidol , we conducted a prospect i ve , r and omized study of violently agitated patients requiring chemical restraint . Patients were r and omized to receive either lorazepam or droperidol i.v . A six-point sedation scale was used . Sedation scores were recorded at time 0 , 5 , 10 , 15 , 30 , and 60 min . Vital signs were compared at time 0 and at 60 min . Repeat dosages of each drug could be given at 30 min . Toxicology screen , ethanol and creatinine phosphokinase levels were obtained . A total of 202 patients were evaluated . One hundred patients received lorazepam and 102 patients received droperidol .  Agitation was attributed to methamphetamine toxicity in 146 patients ( 72 % ) , cocaine toxicity in 28 ( 14 % ) , psychiatric illness in 20 ( 10 % ) , and ethanol withdrawal in 8 ( 4 % ) . Ethanol intoxication was present in 98 patients ( 49 % ) . Both drugs had similar sedation profiles at 5 min . Patients receiving droperidol had significantly lower sedation scores at times 10 , 15 , 30 , and 60 than lorazepam . More repeat doses of lorazepam were given ( 40 ) than droperidol ( 8) at 30 min . We conclude that droperidol produces a more rapid and better sedation than lorazepam at the doses used in this study in agitated patients requiring chemical restraint . Lorazepam is more likely to require repeat dosing than droperidol .  Methamphetamine toxicity was present in the majority of patients in this study Introduction : The purpose of this study was to compare efficacy and safety among intramuscular olanzapine , intramuscular haloperidol , orally disintegrating olanzapine tablets , and oral risperidone solution for agitated patients with psychosis during the first 24 hours of treatment in an acute care psychiatric ward . Methods : Forty-two in patients from an acute care psychiatric ward of a medical center in central Taiwan were enrolled . They were r and omly assigned to 1 of the 4 treatment groups ( 10-mg intramuscular olanzapine , 10-mg olanzapine oral disintegrating tablet , 3-mg oral risperidone solution , or 7.5-mg intramuscular haloperidol ) . Agitation was measured by using the excited component of the Positive and Negative Syndrome Scale ( PANSS-EC ) , the Agitation-Calmness Evaluation Scale , and the Clinical Global Impression-Severity Scale during the first 24 hours . Results : There were significant differences in the PANSS-EC total scores for the 4 intervention groups at 15 , 30 , 45 , 60 , 75 , and 90 minutes after the initiation of treatment . More significant differences were found early in the treatment . In the post hoc analysis , the patients who received intramuscular olanzapine or orally disintegrating olanzapine tablets showed significantly greater improvement in PANSS-EC scores than did patients who received intramuscular haloperidol at points 15 , 30 , 45 , 60 , 75 , and 90 minutes after injection . Conclusions : These findings suggest that intramuscular olanzapine , orally disintegrating olanzapine tablets , and oral risperidone solution are as effective treatments as intramuscular haloperidol for patients with acute agitation . Intramuscular olanzapine and disintegrating olanzapine tablets are more effective than intramuscular haloperidol in the early phase of the intervention . There is no significant difference in effectiveness among intramuscular olanzapine , orally disintegrating olanzapine tablets , and oral risperidone solution Abstract Intramuscular ( IM ) antipsychotics are preferred for efficient control of agitation symptoms . Previous studies have demonstrated that IM ziprasidone is efficacious and safe for treatment of agitation in schizophrenia . However , clinicians now recognize that racial differences may contribute to altered therapeutic response and tolerability . This study compared the efficacy and tolerability of IM ziprasidone versus IM haloperidol for the management of agitation in Chinese subjects with schizophrenia . Subjects with acute schizophrenia were r and omized to either ziprasidone ( n = 189 , 10 to 20 mg as required up to a maximum of 40 mg/d ) or haloperidol ( n = 187 , 5 mg every 4 to 8 hours to a maximum of 20 mg/d ) for 3 days . Psychiatric assessment s and adverse events were assessed at baseline , 2 , 4 , 24 , 48 , and 72 hours . In the ziprasidone group , 2.1 % of subjects discontinued versus 3.7 % in the haloperidol group . The least squares mean change ( SE ) from baseline to 72 hours in Brief Psychiatry Rating Scale total score was −17.32 ( 0.7 ) for ziprasidone ( n = 167 ) and −18.44 ( 0.7 ) for haloperidol ( n = 152 ) , with a 95 % confidence interval treatment difference of −0.7 to 2.9 . Fewer subjects experienced adverse events after ziprasidone ( n = 54 , 28.6 % ) than haloperidol ( n = 116 , 62.0 % ) , with a notably higher incidence of extrapyramidal symptoms in the haloperidol group ( n = 69 , 36.9 % ) compared to the ziprasidone group ( n = 4 , 2.1 % ) . For controlling agitation in schizophrenia in this Chinese study , ziprasidone had a favorable tolerability profile and comparable efficacy and safety compared to haloperidol BACKGROUND The MacArthur Violence Risk Assessment Study ( MacVRAS ) in the USA provided strong evidence to support an actuarial approach in community violence risk assessment . AIMS To examine the predictive accuracy of the MacVRAS measures , in addition to structured professional judgement , in a UK sample of patients discharged from in-patient care in the north-west of Engl and . METHOD A prospect i ve study of 112 participants assessed pre-discharge and followed up at 24 weeks post-discharge . Pre-discharge measures were compared with prevalence of violent behaviour to determine predictive validity of risk factors . RESULTS Historical measures of risk and measures of psychopathy , impulsiveness and anger were highly predictive of community violence . The more dynamic clinical and risk management factors derived from structured professional judgement ( rated at discharge ) added significant incremental validity to the historical factors in predicting community violence . CONCLUSIONS Although static measures of risk relating to past history and personality make an important contribution to assessment of violence risk , consideration of current dynamic factors relating to illness and risk management significantly improves predictive accuracy OBJECTIVES New treatment options for dementia and its behavioral disturbances have become available since publication of The Expert Consensus Guidelines on the Treatment of Agitation in Older Persons with Dementia in 1998 . While only 2 cholinesterase inhibitors , donepezil and tacrine , were available in 1998 , 3 new cognitive-enhancing agents have been introduced since that time as well as several new atypical antipsychotics and antidepressants . However , there are still limited data from controlled studies to guide clinicians in choosing among these agents and sequencing and combining treatments . We therefore conducted a new survey study of expert opinion on the treatment of cognitive impairment and behavioral disturbances associated with dementia . METHODS Based on a literature review , a 61- question survey was developed with 1,225 options . Most options were scored using a modified version of the R AND 9-point scale for rating appropriateness of medical decisions . For other options , the experts were asked to write in answers . The survey was sent to 50 North American experts on dementia , 100 % of whom completed it . In analyzing responses to items rated on the 9-point scale , consensus was defined as a nonr and om distribution of scores by chi-square " goodness-of-fit " test . Based on the 95 % confidence interval around the mean , we assigned a categorical rank ( first line/preferred , second line/alternate , third line/usually inappropriate ) to each option . Guidelines indicating preferred treatment strategies were then developed for selected clinical situations . RESULTS For patients at risk for dementia , the experts recommended control of hypertension and diabetes . They also recommended aspirin and would consider a lipid-lowering agent in patients at risk for vascular dementia . Cholinesterase inhibitors were an option for patients with mild cognitive impairment ( i.e. , at risk for Alzheimer 's dementia [ AD ] ) . To slow cognitive impairment in mild/moderate AD , the experts recommended a cholinesterase inhibitor alone or combined with vitamin E. Donepezil and  galantamine  were the preferred cholinesterase inhibitors . The experts recommended combining a cholinesterase inhibitor with a N-methyl-D-aspartate ( NMDA ) antagonist ( e.g. , memantine ) if a patient with mild/moderate dementia has an inadequate response to monotherapy . Control of hypertension and diabetes was the treatment of choice , in patients with mild/moderate vascular or mixed AD/vascular dementia , with aspirin another first-line option . Cholinesterase inhibitors were also a first-line option for mild/moderate mixed AD/vascular dementia . Among nonpharmacological interventions for mild/moderate dementia , the experts recommended caregiver education , supportive therapy for caregivers , referral to day treatment , exercise programs , and respite care . For moderate/severe AD or mixed AD/vascular dementia , the experts recommended combining an NMDA antagonist with a cholinesterase inhibitor . For moderate/severe vascular or mixed AD/vascular dementia , they recommended control of hypertension and diabetes . The experts ' ratings underscore the importance of nonpharmacological strategies aim ed at reducing caregiver burden in more severe dementia . Management of agitation and other behavioral disturbances was another focus of this study . The experts recommended using an atypical antipsychotic for agitation associated with delirium , psychosis , aggression , or anger . They would also consider divalproex to manage anger with a risk of physical aggression . Selective serotonin reuptake inhibitors were recommended for the treatment of depression or anxiety in patients with dementia . Benzodiazepines or atypical antipsychotics were viewed as short-term options for acute anxiety .  Trazodone was recommended for insomnia . The experts also gave recommendations concerning dosage levels , duration of treatment , and choice of medications for patients with different complicating conditions . CONCLUSIONS The experts reached high levels of consensus on key steps in treating dementia and associated behavioral disturbances . Within the limits of expert opinion and with the expectation that new research data will take precedence , these guidelines may provide direction for clinicians offering care to patients with dementia Introduction This double-blind , placebo-controlled study investigated the efficacy and safety of intramuscular ( IM ) aripiprazole and IM haloperidol for the treatment of acute agitation in patients with schizophrenia or schizoaffective disorder . Material s and methods Four-hundred and forty-eight patients were r and omized ( 2:2:1 ratio ) to IM aripiprazole 9.75 mg , IM haloperidol 6.5 mg , or IM placebo . Patients could receive up to three injections over the first 24 h , with second and third injections administered ≥2 and ≥4 h , respectively , after the first if deemed clinical ly necessary . Primary efficacy measure was mean change in Positive and Negative Syndrome Scale Excited Component ( PEC ) score from baseline to 2 h. Results Mean improvement in PEC at 2 h was significantly greater for IM aripiprazole ( −7.27 ) vs placebo ( −4.78 ; p<0.001 ) ; IM aripiprazole was noninferior to IM haloperidol ( −7.75 ) on PEC . All secondary efficacy measures showed significantly greater improvements at 2 h for IM aripiprazole and IM haloperidol over placebo . Mean number of injections/patient and percentage of patients requiring benzodiazepines were significantly lower for IM aripiprazole vs placebo ( p<0.01 ) . IM aripiprazole was well tolerated . Extrapyramidal symptom-related adverse events were similar for aripiprazole ( 1.7 % ) and placebo ( 2.3 % ) and lower than with haloperidol ( 12.6 % ) . Conclusion These results show that IM aripiprazole is an effective treatment , comparable to IM haloperidol , and well-tolerated for acute agitation in patients with schizophrenia In a controlled study ,  inpatient violence  was measured during placebo , high-potency ( haloperidol ) and low-potency ( chlorpromazine or clozapine ) neuroleptics . Some patients had a marked increase in violent behavior with the moderately high-dose haloperidol , but not with low-potency neuroleptics . The authors discuss reasons for the increased violence with haloperidol , including akathisia and drug-induced behavioral toxicity 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 OBJECTIVES To compare the efficacy of sedation , need for rescue sedation , rates of respiratory depression , and complications of droperidol , ziprasidone , and midazolam when used for the treatment of emergency department ( ED ) patients requiring sedation for acute undifferentiated agitation . METHODS A prospect i ve , r and omized , double-blind trial of agitated ED patients requiring emergent sedation  was performed . Patients were r and omized to receive droperidol 5 mg , ziprasidone 20 mg , or midazolam 5 mg intramuscularly . Interval measurements were made at 0 , 15 , 30 , 45 , 60 , and 120 minutes and included Altered Mental Status Scale ( AMS ) scores , oxygen saturations , and end-tidal carbon dioxide levels . RESULTS A total of 144 patients were enrolled ; 50 patients received droperidol , 46 received ziprasidone , and 48 received midazolam .  Adequate sedation ( mean AMS score < 0 ) was achieved at 15 minutes in patients receiving midazolam ( mean AMS score , -0.81 ) and 30 minutes for patients receiving droperidol ( mean AMS score , -1.3 ) and ziprasidone ( mean AMS score , -0.74 ) . Rescue medication for sedation was necessary in 38 of 144 patients ( droperidol , 5 of 50 ; ziprasidone , 9 of 46 ; midazolam , 24 of 48 ; p < 0.05 ) . No cardiac dysrhythmias were identified in any treatment group . Respiratory depression that clinical ly required treatment with supplemental oxygen occurred in 21 of 144 patients ( droperidol , 4 of 50 ; ziprasidone , 7 of 46 ; midazolam , 10 of 48 ; p = 0.20 ) . No patients required endotracheal intubation . CONCLUSIONS Acutely agitated ED patients se date d with droperidol or ziprasidone required rescue medications to achieve adequate sedation less frequently than those se date d with midazolam . The onset of adequate sedation is delayed with ziprasidone , relative to the other agents OBJECTIVE This multicenter , r and omized , double-blind , placebo-controlled study evaluated the efficacy and safety of intramuscular ( IM ) aripiprazole in patients with acute agitation with a DSM-IV diagnosis of schizophrenia , schizoaffective disorder , or schizo-phreniform disorder . METHOD Patients were r and omly assigned to IM aripiprazole 1 mg , 5.25 mg , 9.75 mg , or 15 mg ; IM haloperidol 7.5 mg ; or placebo and observed for 24 hours . The primary efficacy measure was mean change in the Positive and Negative Syndrome Scale-Excited Component ( PEC ) score from baseline to 2 hours after initial dosing . Secondary measures included the Agitation-Calmness Evaluation Scale ( ACES ) score . The study was carried out at 50 centers worldwide between April 2002 and January 2003 . RESULTS A total of 357 patients were r and omly assigned to treatment . Intramuscular aripiprazole 5.25 mg , 9.75 mg , and 15 mg and IM haloperidol 7.5 mg demonstrated significantly greater reduction in the primary efficacy measure versus placebo . These changes were statistically significant as early as 45 minutes for the IM aripiprazole 9.75-mg group , with a trend toward significance ( p = .051 ) at 30 minutes . Intramuscular haloperidol 7.5 mg first showed a significant reduction in PEC score versus placebo at 105 minutes . At 30 minutes , significantly more patients responded ( defined as a greater than or equal to 40 % reduction in PEC score ) to IM aripiprazole 9.75 mg versus placebo ( 27 % vs. 13 % , p = .05 ) . Intramuscular aripiprazole 9.75 mg significantly improved agitation , without oversedation , as measured by change in ACES score from baseline to 2 hours versus placebo ( p = .003 ) . No patient discontinued the study because of treatment-emergent adverse events . Extrapyramidal symptoms occurred most frequently in the IM haloperidol group . The most common adverse event in IM aripiprazole recipients was headache . CONCLUSION Intramuscular aripiprazole 9.75 mg is a rapidly effective and well-tolerated alternative to IM haloperidol for the control of agitation , without oversedation , in patients with schizophrenia , schizo-affective disorder , or schizophreniform disorder . CLINICAL TRIALS REGISTRATION Clinical Trials.gov identifier NCT00036127 This double-blind , multicenter study aim ed to investigate the efficacy and safety of aripiprazole 10 , 15 or 20 mg/day versus placebo . Patients requiring inpatient hospitalization for acute exacerbation of schizophrenia were r and omized to once-daily aripiprazole 10 , 15 or 20 mg/day or placebo for 6 weeks . The primary efficacy outcome was the mean change from baseline to Week 6 in the Positive and Negative Syndrome Scale ( PANSS ) Total score ( last observation carried forward ) . Patients with no improvement by Week 3 ( Clinical Global Impression-Global Improvement score > or = 4 ) could transfer to open-label aripiprazole 20mg/day . In total , 420 patients were r and omized to placebo ( n = 108 ) ; aripiprazole 10 mg/day ( n = 106 ) ; 15 mg/day ( n = 106 ) ; or 20 mg/day ( n = 100 ) . Of these , 142 patients ( 34 % ) completed 6 weeks of treatment , 131 ( 31 % ) discontinued to receive open-label aripiprazole , and 147 ( 35 % ) for other reasons . Aripiprazole 10 , 15 and 20 mg/day each showed significantly greater improvements from baseline than placebo for all efficacy measures , including PANSS Total , Positive and Negative scores , and the CGI-Severity of Illness score . Significantly greater improvements in PANSS Total score versus placebo were achieved by Week 1 with 10 or 20 mg/day and Week 3 with 15 mg/day . All three doses were well tolerated . Overall , aripiprazole was not associated with clinical ly meaningful differences in extrapyramidal symptoms , prolactin or weight changes versus placebo . Aripiprazole 10 mg/day is effective and well tolerated for patients experiencing an acute exacerbation of schizophrenia BACKGROUND An intramuscular ( IM ) formulation of olanzapine has been developed because there are no rapid-acting IM atypical antipsychotic drugs currently available in the United States for treating acute agitation in patients with schizophrenia . METHODS Recently hospitalized acutely agitated patients with schizophrenia ( N = 270 ) were r and omized to receive 1 to 3 IM injections of olanzapine ( 2.5 , 5.0 , 7.5 , or 10.0 mg ) , haloperidol ( 7.5 mg ) , or placebo within 24 hours . A dose-response relationship for IM olanzapine in the reduction of agitation was assessed by measuring the reduction in Positive and Negative Syndrome Scale Excited Component ( PANSS-EC ) scores 2 hours after the first injection . Safety was assessed by recording adverse events and with extrapyramidal symptom scales and electrocardiograms at 24 hours after the first injection . RESULTS Olanzapine exhibited a dose-response relationship for reduction in agitation ( F(1,179)= 14.4 ; P<.001 ) . Mean PANSS-EC reductions 2 hours after the first injection of olanzapine ( 2.5 mg = -5.5 ; 5.0 mg = -8.1 ; 7.5 mg = -8.7 ; 10.0 mg = -9.4 ) were superior to those with placebo ( -2.9 ; P = .01 vs olanzapine at 2.5 mg ; P<.001 for each other olanzapine dose ) but not with haloperidol ( -7.5 ) . A dose of 5.0 , 7.5 , or 10.0 mg of olanzapine caused a greater reduction in agitation than placebo 30 minutes after the first injection . There were no differences between treatment groups for hypotension , the most frequently reported adverse event , or for clinical ly relevant changes in the QTc interval . There was a greater incidence of treatment-emergent parkinsonism during treatment with IM haloperidol ( 16.7 % ) than with 2.5 ( P = .03 ) , 5.0 ( P = .03 ) , or 7.5 mg ( P = .01 ) of IM olanzapine ( 0 % ) or with placebo ( 0 % ) ( P = .01 ) . CONCLUSIONS Intramuscular olanzapine at a dose of 2.5 to 10.0 mg per injection exhibits a dose-response relationship in the rapid treatment of acute agitation in patients with schizophrenia and demonstrates a favorable safety profile 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 Behavior and symptoms seen in 48 24‐h periods preceding violent episodes and 93 control observations were studied . Six behaviors were more common before violence : confusion , irritability , boisterousness , physical threats , verbal threats and attacks on objects . A logistic regression equation based on these behaviors in a r and omized half of the observations predicted the occurrence of subsequent violence in 92.1 % of the other half of the sample without any false positives , giving a sensitivity of 81.3 % and a specificity of 100 % . It is concluded that mentally ill people display the same behaviour before violent acts as we would expect in people without such disorder . The potential for short‐term prediction of violence seems good Abstract Rationale : Intramuscular ( IM ) conventional antipsychotics and /or benzodiazepines are effective in the short-term treatment of acutely agitated psychotic patients but may be associated with adverse effects . A short-acting IM formulation of the novel antipsychotic , ziprasidone , which may offer advantages over conventional agents , has been developed . Objective : To compare ziprasidone IM 2 mg ( n=38 ) and 20 mg ( n=41 ) in the acute control and short-term management of agitated psychotic patients . Methods : A prospect i ve , r and omized , double-blind , 24-h study assessed efficacy using the  Behavioral Activity Rating Scale ( BARS ) and the PANSS . The BARS is a vali date d rating scale for the assessment of treatment response in acute agitation associated with psychosis . Following the initial dose , three more doses could be given 4 h apart if needed during the 24-h period . Results : The mean BARS score had decreased 15 min after the first 20 mg IM dose and was statistically significantly lower than the 2 mg group at 30 min post-dose . The improvement with the 20 mg dose increased until 2 h , and was maintained until at least 4 h post-dose ( P<0.001 ) . Two hours after the first injection , almost all of the patients receiving ziprasidone 20 mg were BARS responders compared with just one-third of those receiving 2 mg ziprasidone ( P<0.001 ) . The calming effect of ziprasidone was also evident by the significant reduction in PANSS agitation items ( P<0.05 ) and CGI-severity at 4 h ( P=0.008 ) . Both ziprasidone doses were very well tolerated .  Ziprasidone IM 20 mg was not associated with EPS , dystonia , akathisia , respiratory depression or with excessive sedation . Conclusions : Ziprasidone IM 20 mg substantially and significantly reduced the symptoms of acute agitation in patients with psychotic disorders .  Ziprasidone 20 mg IM was very well tolerated and produced no dystonia or akathisia 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 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 Two studies tested the reliability and validity of the  Overt Agitation Severity Scale ( OASS )  , a new instrument developed to define and objective ly rate the severity of  agitated behavior . The authors postulate that agitation should be conceptualized as vocal and motor behaviors on a continuum of expressions that extends from anxiety to aggression . Content validity through expert agreement was achieved in the development of test construction over a 2-year period . Results of two pilot studies ( n = 25 and n = 14 subjects ) established the reliability and validity of the OASS  to measure agitation severity . The OASS differs from other agitation scales in that it confines its rating exclusively to observable behavioral manifestations of agitation This double-blind clinical trial studied 16 acutely agitated psychotic patients with manic or manic-like symptoms who needed rapid tranquilization and were therefore on maintenance treatment . They were r and omized to receive intramuscular preparations of clonazepam ( 1 to 2 mg ) or haloperidol ( 5 to 10 mg ) at 0 , 0.5 , and 1.0 hours . Both medications produced significant reduction of manic symptoms within two hours of initial treatment ; however , haloperidol produced beneficial results more rapidly than clonazepam . All patients completed the study , with the exception of one haloperidol-treated patient who developed severe parkinsonism . It was concluded that I.M. clonazepam is an effective , safe , but slower-acting alternative to I.M. haloperidol in the treatment of agitated psychiatric patients in need of rapid tranquilization OBJECTIVE The authors evaluated the comparative efficacy and safety of intramuscular olanzapine , intramuscular haloperidol , and intramuscular placebo for the treatment of acute agitation in schizophrenia . METHOD Hospitalized patients with schizophrenia received one to three injections of intramuscular olanzapine , 10 mg , intramuscular haloperidol , 7.5 mg , or intramuscular placebo over a 24-hour period . Agitation was measured with the excited component of the Positive and Negative Syndrome Scale and two additional scales . RESULTS According to scores on the excited component of the Positive and Negative Syndrome Scale , both intramuscular olanzapine and intramuscular haloperidol reduced agitation significantly more than intramuscular placebo 2 and 24 hours following the first injection . Intramuscular olanzapine reduced agitation significantly more than intramuscular haloperidol 15 , 30 , and 45 minutes following the first injection . No patients treated with intramuscular olanzapine experienced acute dystonia , compared with 7 % of those who were treated with intramuscular haloperidol . No significant QT(c ) interval changes were observed in any patients . CONCLUSIONS Intramuscular olanzapine represents a rapid , effective , and safe treatment for acute agitation in schizophrenia We conducted a prospect i ve double-blind study of accelerated dose titration of olanzapine in the treatment of newly admitted acutely agitated patients with schizophrenia . Patients were r and omized to either oral olanzapine ( 10 mg per day ) or oral haloperidol ( 10 mg per day ) , plus lorazepam as needed ( up to 12 mg per day ) . Antipsychotic dosage was increased to 20 mg per day as early as day 3 . Patients were evaluated with the Positive and Negative Syndrome Scale ( PANSS ) Agitation subscale during the first 24 hours of treatment , daily for the first week , then weekly until study completion . Significant within-group improvement was demonstrated in PANSS Agitation scores for both groups as early as 1 hour after initiating therapy ( -5.79 + /- 6.30 for olanzapine and -4.89 + /- 6.05 for haloperidol , P < .001 ) . This study demonstrated that accelerated dose titration of oral olanzapine is as efficacious as oral haloperidol in reducing acute agitation in patients with schizophrenia OBJECTIVE The objective of this study was to assess the efficacy and safety of inhaled loxapine in the treatment of agitation in patients with psychotic disorders . METHOD In this r and omized , double-blind , placebo-controlled study , 129 agitated patients with schizophrenia or schizoaffective disorder ( DSM-IV criteria ) were r and omized to receive in a clinical or hospital setting a single inhalation of 5 or 10 mg of loxapine or placebo administered using the Staccato loxapine for inhalation device . The inhalation device delivered thermally generated drug aerosol to the deep lung for rapid absorption . The primary efficacy measure was change on the Positive and Negative Syndrome Scale-excited component ( PANSS-EC ) 2 hours following treatment . Secondary outcomes included the Clinical Global Impressions-Improvement scale ( CGI-I ) , Behavioral Activity Rating Scale ( BARS ) , and time to first rescue medication . The study was conducted between September 2006 and January 2007 . RESULTS Differences were statistically significant ( P < .05 ) between placebo and both 5-mg and 10-mg doses on the CGI-I and the CGI-I responder analyses at 2 hours and in time to first rescue medication , and they were statistically significant ( P < .05 ) between placebo and 10-mg loxapine on the PANSS-EC 20 minutes after administration continuing through 2 hours and in change from baseline BARS . Three serious adverse events occurred at least 6 days after treatment , but none were judged related to study treatment . The most common adverse events were sedation and dysgeusia ( 22 % and 17 % , respectively , in the 10-mg group , and 14 % and 9 % , respectively , in the placebo group ) . CONCLUSIONS Inhaled loxapine was generally safe and well tolerated and produced rapid improvement in agitated patients with psychotic disorders . Statistically significant differences in efficacy were found for the 10-mg dose compared with placebo , with results suggesting 5 mg may be effective . The delivery of loxapine by inhalation may provide a rapid , well-tolerated option for treating acute psychotic agitation that allows patients to avoid the aversive effects and loss of autonomy often associated with use of intramuscular medications . Further investigation of this new loxapine formulation is warranted . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00369577 Background Patients experiencing an acute decompensation of schizophrenia or bipolar disorder often present in an agitated state . Agitation presents a barrier to therapy , interrupting the typical physician-patient alliance and creating a disruptive , even hazardous , environment . Rapid assessment and effective treatment are necessary to manage agitation and , potentially , to shorten the time to recovery . Methods One hundred forty-eight acutely agitated patients received either : rapid initial dose escalation ( RIDE ) in which up to 40 mg of oral olanzapine was allowed on days 1 and 2 , up to 30 mg on days 3 and 4 , and 5 to 20 mg thereafter ; or usual clinical practice ( UCP ) in which patients received 10 mg/d olanzapine plus up to 4 mg lorazepam on days 1 and 2 , up to 2 mg on days 3 and 4 , and olanzapine 5 to 20 mg/d thereafter . The Positive and Negative Syndrome Scale-Excited Component ( PANSS-EC : poor impulse control , tension , hostility , uncooperativeness , and excitement ) measured at 24 hours was the primary measure . Secondary assessment s of agitation and safety were also performed . Results Agitation improved significantly from baseline for both treatment groups ; however , improvement with the RIDE strategy was superior to UCP . The RIDE group improvement was superior on the primary efficacy measure ( PANSS-Excited ) at 24 hours ; it was superior on all agitation measures at the end of double-blind treatment . Both treatments were well tolerated , with no clinical ly significant differences in safety measures . Treatment was not limited by oversedation and attention improved from baseline in both groups . Conclusions This study demonstrates the value of olanzapine in the treatment of acutely agitated patients . A new approach to olanzapine dosing that exp and s the initial dose range up to 40 mg/d may offer superior efficacy in rapidly and effectively controlling the symptoms of agitation BACKGROUND There is a clear need for effective , well-tolerated intramuscular ( i.m . ) agents for the acute control of agitated psychotic patients . Currently used agents , including conventional antipsychotics and /or benzodiazepines , may be associated with distressing side effects such as extrapyramidal side effects and excessive sedation . OBJECTIVE The objective of this study was to evaluate the efficacy and tolerability of the rapid-acting i.m . formulation of the novel antipsychotic ziprasidone in the treatment of in patients with psychosis and acute agitation ( DSM-IV diagnoses ) . METHOD In a 24-hour , double-blind , fixed-dose clinical trial , patients were r and omly assigned to receive up to 4 injections ( every 2 hours p.r.n . ) of 2 mg ( N = 54 ) or 10 mg ( N = 63 ) of ziprasidone i.m . The Behavioral Activity Rating Scale measured behavioral symptoms at baseline and the response to treatment up to 4 hours after the first i.m . injection . RESULTS Ziprasidone i.m . , 10 mg , rapidly reduced symptoms of acute agitation and was significantly more effective ( p < .01 ) than the 2-mg dose up to 4 hours after the first injection . Patients were calmed but not excessively se date d , and over half were classed as responders 2 hours after the 10-mg dose . No acute dystonia or behavioral disinhibition was reported . One patient who received the 10-mg dose experienced the extrapyramidal side effect akathisia . CONCLUSION Ziprasidone i.m . , 10 mg , is rapidly effective and well tolerated in the short-term management of the agitated psychotic patient . Comparison with a study of identical design comparing 2-mg with 20-mg doses in patients with similar levels of psychopathology suggests that efficacy with 10 mg or 20 mg of ziprasidone i.m . is significant and dose related ABSTRACT Objective : A sub- population analysis of 325 patients with agitation ( Positive and Negative Syndrome Scale Excited Component [ PEC ] score ≥ 15 and ≤ 32 ; score of ≥ 4 on ≥ 2 items ) associated with schizophrenia in a r and omized , double-blind study investigating the efficacy and tolerability of intramuscular ( IM ) aripiprazole 9.75 mg , IM haloperidol 6.5 mg , or IM placebo and the transition to oral therapy . Research design and methods : Over 24 h , patients could receive up to three IM injections ; the second and third administered ≥ 2 and ≥ 4 h , respectively , after the first , if deemed clinical ly necessary . Following IM treatment , oral aripiprazole or haloperidol was administered for 4 days . The primary efficacy measure was the mean change in PEC score from baseline at 2 h. Results : At 2 h , mean improvements in PEC scores with IM aripiprazole ( –8.0 ) were significantly greater versus IM placebo ( –5.7 ; p ≤ 0.01 ) , and similar versus IM haloperidol ( –8.3 ) . Secondary efficacy measures also significantly improved with active IM treatment versus IM placebo . Continuation with oral treatment provided continued efficacy with both active treatments . The safety profiles of IM and oral aripiprazole were similar . The incidence of extrapyramidal symptom-related adverse events was 0 % with IM aripiprazole , 1.6 % with IM placebo and 16.5 % with IM haloperidol . Conclusion : Intramuscular aripiprazole is effective in patients with acute agitation associated with schizophrenia , comparable to IM haloperidol , and enables convenient transfer to oral aripiprazole therapy STUDY OBJECTIVE To compare the utility of intramuscular lorazepam ( LZ ) with the combination of intramuscular haloperidol ( HDL ) and LZ to control  acutely agitated behavior .  DESIGN R and omized double-blind comparison . SETTING Psychiatric emergency service of a large , university-affiliated , municipal hospital . PATIENTS Twenty subjects treated on the psychiatric emergency service . INTERVENTIONS Patients received an injection of either LZ 2 mg ( 11 patients ) or HDL 5 mg plus LZ 2 mg ( 9 patients ) . The Overt Aggression Scale ( OAS ) , visual analog scales reflecting agitation and hostility , and the Clinical Global Impressions ( CGI ) severity scale were administered at baseline and 30 , 60 , 120 , and 180 minutes after the injection . MEASUREMENTS AND MAIN RESULTS Planned data comparisons included categoric assignment of patients as improved , as defined by decreases in outcome measures 60 minutes after the injection , as well as continuous variables up to 180 minutes after the injection . A significantly greater percentage of subjects receiving combined treatment improved on the specific measures 60 minutes after dosing ( p<0.05 ) . Kaplan-Meier survival analyses showed significant between-group differences in survival curves plotted for the entire study period ( p<0.05 ) . Repeated measures analyses of variance study ing group differences showed that both groups improved over time , but between-group differences were not significant . The powers of these analyses were low due to the small sample . No serious adverse effects occurred in either treatment group . CONCLUSION Our results suggest superior efficacy for HDL-LZ over LZ alone . Categoric tests of improvement at 60 minutes provided the strongest evidence of group differences Agitation is a vexing problem frequently observed in emergency department acute psychiatric patients , yet no instruments to measure agitation in this setting and population were found upon review of the literature . Previously developed agitation rating scales are limited by the length of observation they require , their need for participation by the patient , complexity in scoring , and a lack of validity in this setting and population . The purpose of this study was to psychometrically evaluate and refine an observation-based agitation scale for use with emergency department acute psychiatric patients . Using a method ological design , the 21-item Agitation Severity Scale was utilized to assess 270 adult psychiatric patients in the emergency setting in a prospect i ve , observational fashion . Reliability analysis , item analysis , exploratory factor analysis , and validity assessment s were completed . The relationship between Agitation Severity Scale scores and scores on the previously established Overt Agitation Severity Scale was evaluated . The instrument was reduced to 17 items representing four factors ( Aggressive Behaviors , Interpersonal Behaviors , Involuntary Motor Behaviors , and Physical Stance ) that accounted for nearly 70 % of observed variance , Cronbach 's & agr ; = 0.91 . Evidence of internal consistency reliability , equivalence reliability , construct validity , and convergent validity was established . Through this study , the 17-item Agitation Severity Scale demonstrated acceptable levels of reliability and validity when used with acute psychiatric patients in the emergency setting . This instrument holds promise as a method of enhancing clinical communication about agitation , evaluating the efficacy of interventions aim ed at decreasing agitation , and as a research tool STUDY OBJECTIVE Parenteral benzodiazepines or antipsychotics are often used to manage acute agitation in emergency department ( ED ) setting s in which alternative strategies have failed or are not feasible . There are scant data comparing parenteral medication regimens . We aim to determine the efficacy and safety of intravenous droperidol or olanzapine as an adjunct to intravenous midazolam for rapid patient sedation . METHODS We undertook a r and omized , double-blind , placebo-controlled , double-dummy , clinical trial in 3 EDs ( August 2009 to March 2011 ) . Adult patients ( n=336 ) requiring intravenous drug sedation for acute agitation were r and omized to receive a saline solution ( control ) , droperidol ( 5 mg ) , or olanzapine ( 5 mg ) bolus . This was immediately followed by incremental intravenous midazolam boluses ( 2.5 to 5 mg ) until sedation was achieved . The primary outcome was time to sedation . Secondary outcomes were need for " rescue " drugs and adverse events . RESULTS Three hundred thirty-six patients were r and omized to the 3 groups . Baseline characteristics were similar across groups . The differences in medians for times to sedation between the control and droperidol and control and olanzapine groups were 4 minutes ( 95 % confidence interval [ CI ] 1 to 6 minutes ) and 5 minutes ( 95 % CI 1 to 6 minutes ) , respectively . At any point , patients in the droperidol and olanzapine groups were approximately 1.6 times more likely to be se date d compared with controls : droperidol and olanzapine group hazard ratios were 1.61 ( 95 % CI 1.23 to 2.11 ) and 1.66 ( 95 % CI 1.27 to 2.17 ) , respectively . Patients in the droperidol and olanzapine groups required less rescue or alternative drug use after initial sedation . The 3 groups ' adverse event profiles and lengths of stay did not differ . CONCLUSION Intravenous droperidol or olanzapine as an adjunct to midazolam is effective and decreases the time to adequate sedation compared with midazolam alone 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 There are no rapid-acting intramuscular formulations of atypical antipsychotics available for quickly calming an agitated patient with bipolar disorder . In this study , 201 agitated patients with bipolar mania were r and omly assigned to receive one to three injections of the atypical antipsychotic olanzapine ( 10 mg , first two injections ; 5 mg , third injection ) , the benzodiazepine lorazepam ( 2 mg , first two injections ; 1 mg , third injection ) , or placebo ( placebo , first two injections ; olanzapine , 10 mg , third injection ) within a 24-hour period . Agitation was measured at baseline , every 30 minutes for the first 2 hours , and at 24 hours after the first injection using the Positive and Negative Syndrome Scale – Excited Component subscale and two additional agitation scales . At 2 hours after the first injection , patients treated with olanzapine showed a significantly greater reduction in scores on all agitation scales compared with patients treated with either placebo or lorazepam . At 24 hours after the first injection , olanzapine remained statistically superior to placebo in reducing agitation in patients with acute mania , whereas patients treated with lorazepam were not significantly different from those treated with placebo or olanzapine . Furthermore , no significant differences among the three treatment groups were observed in safety measures , including treatment-emergent extrapyramidal symptoms , the incidence of acute dystonia , or QTc interval changes . These findings suggest that intramuscular olanzapine is a safe and effective treatment for reducing acute agitation in patients with bipolar mania A comparison of loxapine and haloperidol parenterally in acute psychotic , agitated patients was carried out as a r and omized double‐blind trial . The trial covered 15 patients in each group , and the diagnoses were psychogenic psychosis ( 18 cases ) and acute schizophrenia ( 12 cases ) . The patients received 25–50 mg loxapine or 2.5–5 mg haloperidol combined with biperiden 2.5–5 mg every 6–12 hours over a 72‐hour period . The average daily dose was 130 mg loxapine or 12 mg haloperidol BACKGROUND Aripiprazole is an investigational agent for treating schizophrenia that has a novel pharmacologic profile . The present study investigated the efficacy , safety , and tolerability of aripiprazole and haloperidol compared with placebo . METHOD A 4-week , double-blind , r and omized study , conducted at 36 U.S. centers between July 1997 and June 1998 , compared aripiprazole ( 15 mg/day , 30 mg/day ) to placebo , with haloperidol ( 10 mg/day ) as an active control . Fixed doses of each agent were administered from day 1 throughout the study . A total of 414 patients with a primary DSM-IV diagnosis of schizophrenia or schizoaffective disorder were r and omized .  Efficacy measures included the Positive and Negative Syndrome Scale ( PANSS ) total , PANSS positive , PANSS negative , PANSS-derived Brief Psychiatric Rating Scale ( BPRS ) core , Clinical Global Impressions (CGI)-Severity of Illness , and mean CGI-Improvement scores . Safety and tolerability evaluations included extrapyramidal symptoms ( EPS ) , weight gain , serum prolactin level , and QTc interval . RESULTS Both doses of aripiprazole and haloperidol , 10 mg , produced statistically significant ( p < or = .05 ) improvements from baseline in PANSS total , PANSS positive , PANSS-derived BPRS core , and CGI-Severity scores and significantly lower CGI-Improvement scores at endpoint , compared with placebo . Aripiprazole , 15 mg , and haloperidol , 10 mg , significantly improved PANSS negative score compared with placebo . Both aripiprazole doses and haloperidol separated from placebo for PANSS total scores at week 2 . Unlike haloperidol , aripiprazole was not associated with significant EPS or prolactin elevation at endpoint compared with placebo . There were no statistically significant differences in mean changes in body weight across the treatment groups versus placebo , and no patients receiving aripiprazole experienced clinical ly significant increases in QTc interval . CONCLUSION Aripiprazole , effective against positive and negative symptoms , is a safe and well-tolerated potential treatment for schizophrenia and schizoaffective disorder Abstract Objective To compare two widely used drug treatments for people with aggression or agitation due to mental illness . Design Pragmatic , r and omised clinical trial . Setting Three psychiatric emergency rooms in Rio de Janeiro , Brazil . Subjects 301 aggressive or agitated people . Interventions Open treatment with intramuscular midazolam or intramuscular haloperidol plus promethazine . Main outcome measures Patients tranquil or se date d at 20 minutes . Secondary outcomes : patients tranquil or asleep by 40 , 60 , and 120 minutes ; restrained or given extra drugs within 2 hours ; severe adverse events ; another episode of agitation or aggression ; needing extra visits from doctor during first 24 hours ; overall antipsychotic load in first 24 hours ; and not discharged by two weeks . Results 151 patients were r and omised to midazolam , and 150 to haloperidol-promethazine mix . Follow up for the primary outcome was available for 298 ( 99 % ) : 134/151 ( 89 % ) of patients given midazolam were tranquil or asleep after 20 minutes compared with 101/150 ( 67 % ) of those given haloperidol plus promethazine ( relative risk 1.32 ( 95 % confidence interval 1.16 to 1.49 ) ) . By 40 minutes , midazolam still had a statistically and clinical ly significant 13 % relative advantage ( 1.13 ( 1.01 to 1.26 ) ) . After 1 hour , about 90 % of both groups were tranquil or asleep . One important adverse event occurred in each group : a patient given midazolam had transient respiratory depression , and one given haloperidol-promethazine had a gr and e mal seizure . Conclusions Both treatments were effective . Midazolam was more rapidly sedating than haloperidol-promethazine , reducing the time people are exposed to aggression . Adverse effects and re sources to deal with them should be considered in the choice of the treatment 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 The treatment of agitation in drug- and alcohol-using emergency patients is understudied . METHOD We performed a retrospective chart review of 105 agitated emergency department patients who received either intramuscular ( IM ) haloperidol or IM olanzapine  , comparing prescribing patterns , level of agitation , response to treatment and side effects in patients positive for drugs or alcohol [ D/A(+ ) ] and patients negative for drugs or alcohol [ ( D/A(- ) ] . RESULTS The haloperidol-benzodiazepine combination was the most frequently prescribed treatment in both groups , although alcohol(+ ) status biased clinicians toward using haloperidol alone . Overall , D/A(+ ) and D/A(- ) patients responded to the initial intervention at similar rates , although D/A(+ ) patients were rated as more agitated and had more posttreatment sedation than D/A(- ) patients . In D/A(+ ) patients , haloperidol+benzodiazepine and IM olanzapine performed better than haloperidol alone . There were no serious adverse events with any treatment . CONCLUSION Findings support the generalization of efficacy data from more rarified agitated sample s to population s with high rates of substance use and highlight the need for prospect i ve , inclusive , r and omized trials comparing the commonly used haloperidol-benzodiazepine combination with newer injectable antipsychotics Objective . To compare oral risperidone and intramuscular ( IM ) haloperidol , both in combination with IM lorazepam , in the management of acute agitation and psychosis in the medical emergency department . Methods . In this prospect i ve , r and omized , placebo-controlled , double-blind study of 30 patients presenting to the emergency department with acute agitation and /or psychosis , three groups of 10 patients received oral and IM medications : 1 ) 2 mg oral risperidone and 2 mg IM lorazepam ; 2 ) 5 mg oral haloperidol and 2 mg IM lorazepam ; 3 ) oral placebo and 2 mg IM lorazepam . Each treatment group received both an injection and a tablet to reduce treatment group variability . Patients were evaluated using the Brief Psychiatric Rating Scale ( BPRS ) and the Positive and Negative Syndrome Scale ( PANSS ) before receiving medication and at 30 and 90 minutes after medication was administered . The intergroup mean percent reductions in rating scale scores were compared using ANOVA , chi-square , and Kruskal-Wallis tests . Results . There were no statistically significant differences among the groups at any point . The two groups receiving an antipsychotic plus lorazepam showed a trend towards increased symptom reduction compared with the group receiving lorazepam alone , although this trend was not statistically significant . Conclusions . Lorazepam alone was as effective as lorazepam plus haloperidol or lorazepam plus risperidone in this small trial . While not statistically significant , a trend toward better outcomes with combined treatment warrants further study STUDY OBJECTIVE We compare intravenous midazolam and droperidol for the onset of sedation of acutely agitated patients in the emergency department ( ED ) . METHODS This was a double-blind , r and omized , clinical trial set in the ED of a university teaching hospital . Subjects were adults , acutely agitated because of mental illness , intoxication , or both , who received midazolam or droperidol , 5 mg intravenously , every 5 minutes until se date d. We analyzed time to sedation using survival analysis , median times to sedation , and proportions se date d at 5 and 10 minutes . RESULTS Seventy-four patients received midazolam ; 79 patients , droperidol .  Survival analysis showed no difference in time to sedation ( hazard ratio 0.86 ; 95 % confidence interval [ CI ] 0.61 to 1.23 ) , P=.42 . Median time to sedation was 6.5 minutes for midazolam ( median dose 5 mg ) and 8 minutes for droperidol ( median dose 10 mg ) , P=.075 ( effect size 1.5 minutes ; 95 % CI 0 to 4 minutes ) . At 5 minutes , 33 of 74 ( 44.6 % ) patients from the midazolam group were adequately se date d compared with 13 of 79 ( 16.5 % ) patients from the droperidol group , a difference of 28.1 % ( 95 % CI 12.9 % to 43.4 % ; P<.001 ) . By 10 minutes , 41 of 74 ( 55.4 % ) from the midazolam group were se date d compared to 42 of 79 ( 53.2 % ) from droperidol , a difference of 2.2 % ( 95 % CI -14.9 % to 19.3 % ; P=.91 ) . Eleven adverse events occurred in the midazolam group and 10 in the droperidol group . Three patients required active airway management ( 3 patients with assisted ventilation and 1 patient intubated ) ; all received midazolam . CONCLUSION There is no difference in onset of adequate sedation of agitated patients using midazolam or droperidol . Patients se date d with midazolam may have an increased need for active airway management OBJECTIVE Patients with acute schizophrenia who are agitated typically manifest worse overall symptomatology and are generally more challenging to treat than nonagitated patients . In order to determine whether baseline agitation level influences treatment response , the effects of oral aripiprazole in acute patients with schizophrenia experiencing either higher or lower levels of agitation were examined . METHOD A post hoc analysis of pooled data from the first 4 or 6 weeks of 4 r and omized , double-blind , placebo-controlled aripiprazole trials was conducted . Patients with a DSM-IV diagnosis of acute schizophrenia r and omly assigned to treatment with either aripiprazole 10 , 15 , 20 , or 30 mg/day ( N = 790 ) or placebo ( N = 397 ) were divided into groups experiencing higher or lower agitation at baseline . Higher agitation was defined as a baseline Positive and Negative Syndrome Scale (PANSS)-Excited Component ( PEC ) score of > or = 14 and a score of > or = 4 on at least 1 PEC item ( excitement , hostility , tension , uncooperativeness , or poor impulse control ) . Analysis of covariance was used to evaluate PANSS total , Clinical Global Impressions-Improvement scale ( CGI-I ) , and PEC scores between aripiprazole and placebo within the higher and lower agitation groups . RESULTS In both the higher and lower agitation groups , aripiprazole treatment produced significantly lower PANSS total , CGI-I , and PEC scores at weeks 2 to 6 , compared with placebo ( p < .05 for each measure ) . Percentage of concomitant benzodiazepine use was similar at end point for aripiprazole and placebo , and adverse events were generally mild across groups . CONCLUSIONS Aripiprazole significantly improved the core symptoms of acute schizophrenia regardless of baseline agitation level . In particular , agitation symptoms were significantly decreased in patients with higher baseline agitation . Improvements appeared to be independent of benzodiazepine use or excessive sedation effects . These results suggest that oral aripiprazole is an effective and safe treatment option for patients with acute schizophrenia who manifest agitation symptoms OBJECTIVE To examine the antimanic efficacy of the relatively nonsedating antipsychotic aripiprazole in patients with bipolar I disorder and high or low baseline levels of agitation . METHOD Data were pooled for this post hoc analysis from two 3-week , placebo-controlled trials of aripiprazole in acute mania ( DSM-IV ) . Patients r and omly assigned to aripiprazole 30 mg/day ( N = 259 ) or placebo ( N = 254 ) were classified as having either high ( Positive and Negative Syndrome Scale [ PANSS ] Excited Component [ PEC ] score of > or=14 and a score of > or= 4 on at least one PEC item ) or low ( PEC < 14 ) levels of agitation at baseline .  Efficacy measures were changes in Young Mania Rating Scale ( YMRS ) scores , Clinical Global Impressions-Bipolar ( CGI-BP ) scores , and PEC scores . Efficacy and agitation measurements were assessed by analysis of covariance . RESULTS From the first week of therapy onward , aripiprazole-treated subjects had significantly greater reduction from baseline in YMRS total scores than placebo-treated subjects in both the high- and low-agitation groups ( p < .05 for both groups ) and significantly improved CGI-BP scores vs. placebo at end point ( p < .05 for both ) . In highly agitated patients receiving aripiprazole , PEC scores were significantly decreased versus placebo at end point ( p < .05 ) . In patients with low agitation receiving aripiprazole , no increases in PEC scores were seen , and a significant reduction in agitation symptoms was apparent after adjustment for baseline PEC scores . CONCLUSIONS Aripiprazole was superior to placebo in reducing the severity of both mania and agitation in highly agitated patients with bipolar I disorder and showed significant antimanic activity in patients with low levels of agitation without increasing agitation . These findings suggest that aripiprazole 's antimanic effect is specific and not limited to control of agitation through sedation Objectives . Behavioral emergencies are a common and serious problem for consumers , their communities , and the healthcare setting s on which they rely , but there is little research to guide provider responses to this challenge . Key constructs such as agitation have not been adequately operationalized so that the criteria defining a behavioral emergency are vague . A significant number of deaths of patients in restraint has focused government and regulators on these issues , but a consensus about key elements in the management of behavioral emergencies has not yet been articulated by the provider community . The authors assembled a panel of 50 experts to define the following elements : the threshold for emergency interventions , the scope of assessment for varying levels of urgency and cooperation , guiding principles in selecting interventions , and appropriate physical and medication strategies at different levels of diagnostic confidence and for a variety of etiologies and complicating conditions . Method . A written  survey with 808 decision points was completed by 50 experts . A modified version of the R AND Corporation 9-point scale for rating appropriateness of medical decisions was used to score options . Consensus on each option was defined as a non-r and om distribution of scores by chi-square “ goodness-of-fit ” test . We assigned a categorical rank ( first line/preferred choice , second line/ alternate choice , third line/usually inappropriate ) to each option based on the 95 % confidence interval around the mean rating . Guideline tables were constructed describing the preferred strategies in key clinical situations . Results . The expert panel reached consensus on 83 % of the options . The relative appropriateness of emergency interventions was ascertained for a continuum of behaviors . When asked about the frequency with which emergency interventions  ( parenteral medication , restraint , seclusion ) were required in their services , 47 % of the experts reported that such interventions were necessary for 1%–5 % of patients seen in their services and 32 % for 6%–20 % . In general , the consensus of this panel lends support to many elements of recent regulations from the Health Care Financing Administration ( now the Centers for Medicare and Medicaid Services ) , including the timing of clinician assessment and re assessment and the intensity of nursing care . However , the panel did not endorse the concept of “ chemical restraint , ” instead favoring the idea that medications are treatments for target behaviors in behavioral emergencies even when the causes of these behaviors are not well understood . Control of aggressive behavior emerged as the highest priority during the emergency ; however , preserving the physician-patient relationship was rated a close second and became the top priority in the long term . Oral medications , particularly concentrates , were clearly preferred if it is possible to use them . Benzodiazepines alone were top rated in 6 of 12 situations . High-potency conventional antipsychotics used alone never received higher ratings than benzodiazepines used alone . A combination of a benzodiazepine and an antipsychotic was preferred for patients with suspected schizophrenia , mania , or psychotic depression . There was equal support for high-potency conventional or atypical antipsychotics  ( particularly liquids ) in oral combinations with benzodiazepines .  Droperidol emerged in fourth place in some situations requiring an injection . Conclusions . To evaluate many of the treatment options in this survey , the experts had to extrapolate beyond controlled data . Within the limits of expert opinion and with the expectation that future research data will take precedence , these guidelines provide some direction for addressing common clinical dilemmas in the management of psychiatric emergencies and can be used to inform clinicians in acute care setting s regarding the relative merits of various strategies Patients with methamphetamine toxicity often present to the emergency department ( ED ) agitated , violent and psychotic . To determine the efficacy of a benzodiazepine versus a butyrophenone for chemical restraint we conducted a prospect i ve , r and omized study at a large urban university ED between January 1995 and January 1997 . Patients were r and omized to receive either lorazepam or droperidol intravenously . A 6-point sedation scale was devised , with 6 representing extreme agitation and 1 deep sleep . Sedation scores were recorded at time 0 , 5 , 10 , 15 , 30 and 60 min . Vital signs were recorded at time 0 and at 60 min . If sedation was inadequate , repeat dosages of each drug could be repeated at 30 min . Toxicology screen , ethanol and creatinine phosphokinase levels were obtained . A total of 146 patients were evaluated . Seventy-four patients received lorazepam  and 72 received  droperidol . Both drugs had similar sedation profiles at 5 min . Patients receiving droperidol had significantly improved sedation scores at times 10 , 15 , 30 and 60 min than lorazepam ( p < 0.001 ) . More repeat doses of lorazepam were given ( 26 ) than droperidol ( 6 ) at 30 min . Both drugs produced significant reduction in pulse , systolic blood pressure , respiratory rate , and temperature over 60 min . We conclude droperidol produces a more rapid and profound sedation than lorazepam for methamphetamine toxicity . Lorazepam is more likely to require repeat dosing than droperidol Abstract Studies of intramuscular ( IM ) olanzapine in Asian and Taiwanese population s are limited . This study examined the efficacy and safety of IM olanzapine in Taiwanese patients with schizophrenia and acute agitated behavior . This was a multicenter , double-blind , r and omized , parallel study comparing the efficacy and safety of 10 mg/d IM olanzapine ( n = 25 ) against 7.5 mg/d haloperidol ( n = 24 ) . The primary objective was to assess the change of agitation from baseline to 2 hours after the first IM injection on the Positive and Negative Symptom Scale – Excited Component Scale . The changes of Positive and Negative Symptom Scale – Excited Component Scale score from baseline to 2 hours after the first IM injection did not show statistically significant difference between study groups ( olanzapine −9.0 ± 5.7 , haloperidol −7.9 ± 4.0 , P = 0.254 ) . Both groups reported insomnia as the most common treatment-emergent adverse event , and no serious adverse event was reported . Intramuscular olanzapine and IM haloperidol are similarly effective antipsychotic agents in treating agitated symptoms in Taiwanese patients with schizophrenia . Both IM olanzapine and IM haloperidol were proven to be safe and well tolerated , which also provided alternative options in the treatment of patients with schizophrenia with agitation Behavioral agitation and prominent positive psychotic symptoms often characterize the acute presentation of schizophrenia . The clinical treatment goal is a rapid control of these symptoms . The relative efficacy of olanzapine , a novel antipsychotic drug , was compared with that of the conventional antipsychotic drug haloperidol . A post hoc analysis conducted on a large multicenter , double-blind , 6-week study of acute-phase patients with DSM-III-R schizophrenia or schizophreniform or schizoaffective disorders treated with olanzapine ( 5 - 20 mg/day ) or haloperidol ( 5 - 20 mg/day ) assessed the treatment effects on agitation ( Brief Psychiatric Rating Scale [ BPRS ] agitation score ) and positive symptoms ( BPRS positive symptom score ) . Overall , olanzapine-treated patients experienced significantly greater improvement in behavioral agitation than did haloperidol-treated patients ( last observation carried forward [ LOCF ] ; p < .0002 ) . Both groups showed similar reductions in agitation scores during the first 3 weeks of therapy ; olanzapine was associated with significantly greater improvements at weeks 4 , 5 , and 6 ( observed cases [ OC ] ) . Similarly , patients with predominantly positive psychotic symptoms experienced significantly greater improvement in BPRS positive symptom scores with olanzapine compared with haloperidol ( LOCF ; p = .013 ) . In olanzapine-treated patients , improvement in BPRS agitation and positive symptom scores was significantly greater at weeks 4 , 5 , and 6 ( agitation scores , p < or = .01 ; positive symptom scores , p < .05 ) ( OC ) . These data suggest that olanzapine may be considered a first-line treatment for the patient in an acute episode of schizophrenia BACKGROUND Aripiprazole is a dopamine D2 receptor partial agonist with partial agonist activity at serotonin 5HT1A receptors and antagonist activity at 5HT2A receptors . This multicenter trial examined the efficacy , safety , and tolerability of aripiprazole in patients with acute exacerbation of schizophrenia or schizoaffective disorder . METHODS In this 4-week double-blind study , 404 patients were r and omized to 20 mg/d ( n = 101 ) or 30 mg/d ( n = 101 ) of aripiprazole , placebo  ( n = 103 ) , or 6 mg/d of risperidone  ( n = 99 ) . Efficacy assessment s included Positive and Negative Syndrome Scale ( PANSS ) scores and Clinical Global Impression scores . Safety and tolerability evaluations included extrapyramidal symptoms and effects on weight , prolactin , and corrected QT ( QTc ) interval . RESULTS Aripiprazole ( 20 and 30 mg/d ) and risperidone ( 6 mg/d ) were significantly better than placebo on all efficacy measures . Separation from placebo occurred at week 1 for PANSS total and positive scores with aripiprazole and risperidone and for PANSS negative scores with aripiprazole . There were no significant differences between aripiprazole and placebo in mean change from baseline in the extrapyramidal symptom rating scales . Mean prolactin levels decreased with aripiprazole but significantly increased 5-fold with risperidone .  Mean change in QTc interval did not differ significantly from placebo with any active treatment group . Aripiprazole and risperidone groups showed a similar low incidence of clinical ly significant weight gain . CONCLUSIONS Aripiprazole is effective , safe , and well tolerated for the positive and negative symptoms in schizophrenia and schizoaffective disorder . It is the first non-D2 receptor antagonist with clear antipsychotic effects and represents a novel treatment development for psychotic disorders INTRODUCTION Patterns of use of antipsychotics are not well described in emergency units . The objective of this study was to describe the effectiveness and safety of use of olanzapine in patients with acute psychosis and agitation in the emergency rooms . METHODS In this prospect i ve observational study 278 patients with acute psychosis and agitation were consecutively admitted in 16 psychiatric emergency wards and treated with any oral psychopharmacology treatment , including olanzapine  , according to investigators clinical criteria . Data were collected prospect ively including demographics , diagnosis , concomitant medications , utilization of mechanical restraints , and severity of agitation . Clinical evolution during emergency room stay was assessed with PANSS-Excitement Component , CGI-S and Agitation and Calmness Evaluation Scale ( ACES ) at baseline , before any re-intervention ( if needed ) and at discharge from the emergency room . Safety was also evaluated . RESULTS Olanzapine alone was used in 148 ( 53.2 % ) patients . Most of them ( 77.7 % ) were diagnosed of Schizophrenia and related psychoses . Up to 38 patients ( 25.7 % ) required mechanical restraints . Mean change ( confidence interval [ CI ] 95 % ) from baseline to discharge was significant in all rating scales ; PANSS-EC : -7.46 ( -8.2 , -6.7 ) ; CGI-S : -1.82 ( -2 , -1.6 ) ACES : 1.28 ( 1.1 , 1.5 ) . At discharge 70.3 % of patients went to inpatient units . Five patients ( 3.4 % ) reported adverse events including : bradycardia , dry mouth , sedation , hypertension , hypotension , and orthostatic hypotension . None of them was serious . CONCLUSIONS The utilization of olanzapine alone decreased agitation in psychotic patients in emergency room setting s. Incidence of adverse events was low and it was well tolerated BACKGROUND This study compared the safety , tolerability and switch to oral medication in patients with bipolar disorder or schizophrenia who received intramuscular ( IM ) olanzapine or other IM antipsychotics for the treatment of acute agitation . METHODS Patients ( N = 2011 ) from 15 countries participated in this prospect i ve , observational , non-interventional study . In patients requiring treatment with at least one IM injection of a short-acting antipsychotic  were assessed at baseline and within 7 days after the first IM injection . Treatment groups comprised : ( i ) patients prescribed IM olanzapine at baseline ; and ( ii ) patients prescribed any other IM antipsychotic medication at baseline . Outcome measures included : treatment-emergent adverse events , concomitant psychotropic medication and the time taken to switch to oral medication . RESULTS Fewer patients in the IM olanzapine group experienced an adverse event than patients in the other IM antipsychotic group ( 34.4 % vs. 46.2 % , p < 0.001 ) . The most frequently reported adverse events in both groups were : sedation , Parkinsonism , disturbance in attention , akathisia , dystonia and orthostatic hypotension . Fewer patients in the IM olanzapine group used anticholinergics ( 13.9 % vs. 42.5 % , p < 0.001 ) or anxiolytics/hypnotics ( 47.6 % vs. 51.6 % , p = 0.023 ) . Patients in the IM olanzapine group switched to oral medication earlier than patients in the other IM antipsychotic group ( median time = 46.5 vs. 48.0 h , p = 0.009 ) . CONCLUSIONS These findings suggest that IM olanzapine may have a favourable impact on individual patients . However , the high rate of oral concomitant medication used throughout the study limits these findings from being associated with IM olanzapine alone STUDY OBJECTIVE To assess acute efficacy and safety of 9.75 mg of intramuscular ( IM ) injections of the atypical antipsychiatric aripiprazole in patients with schizophrenia or bipolar disorder and acute agitation . DESIGN Open-label trial of IM injections of aripiprazole and 24-hour monitoring of clinical response in patients with major psychoses and acute agitation . Partial analysis of blood levels of the administered drug to correlate with clinical response . SETTING Acute psychiatric care wards in a single university hospital . PATIENTS A total of 201 acutely agitated patients ( 79 with schizophrenia and 122 with bipolar disorder I ) . INTERVENTION Aripiprazole 9.75 mg IM injection . MEASUREMENTS AND MAIN RESULTS We evaluated clinical response using the Excitatory Component of the Positive and Negative Syndrome Scale ( PANSS-EC ) , the Agitation/Calmness Evaluation Scale ( ACES ) , and the Clinical Global Impressions scale ( CGI ) . Assessment s were conducted 30 , 60 , 90 , and 120 minutes and 24 hours after the first injection for PANSS-EC and ACES , and 2 , 4 , 6 , and 24 hours for CGI . Response was at least a 40 % decrease in PANSS-EC scores . We measured serum aripiprazole and dehydroaripiprazole levels in a sub sample . IM aripiprazole significantly improved clinical measures . PANSS-EC improved progressively , starting after 30 minutes . ACES improved after 90 minutes and continued thereafter . Effects were sustained , with steadily decreasing CGI scores , until the 24th hour . Response rate was 83.6 % after 2 hours , but with repeat injections , it rose to over 90 % with no differences among diagnostic groups . Although there were gender differences in the response to individual PANSS-EC items , the responses were similar overall . Neither clinical monitoring nor patient reporting revealed any side effects . No therapeutic window was identified , and levels did not correlate with any clinical measure . CONCLUSION Aripiprazole was effective and safe in reducing acute agitation in patients with bipolar disorder or schizophrenia . Our results compare favorably to double-blind trials , probably due to higher expectations in trials involving no placebo arm . Absence of side effects could be related to the short observation time Five fixed doses of the atypical antipsychotic " Seroquel " ( quetiapine ) were evaluated to delineate a dose-response relationship , as measured by changes from baseline in Brief Psychiatric Rating Scale ( BPRS ) , Clinical Global Impression ( CGI ) , and Modified Scale for the Assessment of Negative Symptoms ( SANS ) summary scores , and to compare efficacy and tolerability opposite placebo and haloperidol .  Three hundred sixty-one patients from 26 North American centers entered this double-blind , placebo-controlled trial with acute exacerbation of chronic schizophrenia ( DSM-III-R ) . Patients who completed a single-blind , placebo washout phase were r and omized to double-blind treatment with quetiapine ( 75 , 150 , 300 , 600 , or 750 mg daily ) , haloperidol ( 12 mg daily ) , or placebo and evaluated weekly for 6 weeks . At end point , significant differences ( p < 0.05 , analysis of covariance ) in adjusted mean changes from baseline were identified between the four highest doses of quetiapine and placebo for BPRS total , BPRS positive-symptom cluster , and CGI Severity of Illness item scores and between quetiapine 300 mg and placebo for SANS summary score . Differences between quetiapine and haloperidol were not significant . Dose-response modeling showed significant linear and quadratic functions of quetiapine dose for all primary efficacy variables . Notably , no significant safety concerns were identified as dose increased . Quetiapine was no different from placebo across the dose range studied regarding incidence of extrapyramidal symptoms or change in prolactin concentrations .  Quetiapine is well tolerated and clinical ly effective in the treatment of schizophrenia . It is both superior to placebo and comparable to haloperidol in reducing positive symptoms at doses ranging from 150 to 750 mg/day and in reducing negative symptoms at a dose of 300 mg/day Rationale Conventional intramuscular ( IM ) antipsychotics used in managing acute exacerbation of schizophrenia are associated with side effects such as acute dystonia . Objectives To compare the efficacy and tolerability of sequential IM/oral ziprasidone with haloperidol in acute exacerbation of schizophrenia or schizoaffective disorder . Methods In a 6-week , multicenter , parallel-group , flexibly dosed study , patients were r and omized to ziprasidone ( IM up to 3 days , then oral 40–80 mg , b.i.d . ) or haloperidol ( IM up to 3 days , then oral 5–20 mg/day ) . Assessment s were rater-blinded . Results At the end of IM treatment , patients receiving ziprasidone ( n=427 ) showed significantly improved Brief Psychiatric Rating Scale Total ( BPRS total ) scores compared with those receiving  haloperidol ( n=138 ) [ least-squares ( LS ) mean change −6.14 for ziprasidone versus −4.13 for haloperidol , P<0.0018 ] . At endpoint , there were no significant between-group differences in BPRS total scores . There was a significantly greater improvement in BPRS negative subscale scores in ziprasidone-treated patients , both at the end of IM treatment ( LS mean change −1.15 for ziprasidone and −0.28 for haloperidol , P<0.0001 ) and at study endpoint ( LS mean change −2.94 for ziprasidone and −2.24 for haloperidol , P<0.0001 ) .  Haloperidol-treated  patients exhibited significantly greater increases in Extrapyramidal Symptom Rating Scale at end of IM treatment and at endpoint ( P<0.0001 ) . They also had significantly higher ratings on the Barnes Akathisia Scale ( P<0.0001 ) and the Movement Disorder Burden Score ( P<0.005 ) , as well as higher incidences of movement disorder-related adverse events . Conclusions Sequential IM and oral ziprasidone offers important efficacy and tolerability advantages over haloperidol in acute schizophrenia BACKGROUND This 7-day , r and omized , open-label , multicenter , international study compared the efficacy and tolerability of intramuscular ( i.m . ) ziprasidone with haloperidol i.m . and the transition from i.m . to oral treatment in hospitalized patients with acute psychotic agitation ( related to DSM-III-R diagnoses ) . METHOD Patients received up to 3 days of flexible-dose ziprasidone i.m . ( N = 90 ) or haloperidol i.m . ( N = 42 ) followed by oral treatment to day 7 . After an initial ziprasidone i.m . dose of 10 mg , subsequent i.m . doses of 5 to 20 mg could be given every 4 to 6 hours ( maximum daily dose = 80 mg ) if needed , followed by oral ziprasidone , 80 - 200 mg/day . Haloperidol i.m . doses of 2.5 to 10 mg were given on entry , followed by 2.5 to 10 mg i.m . every 4 to 6 hours ( maximum daily dose = 40 mg ) if needed , then by oral haloperidol , 10 - 80 mg/day . RESULTS The mean reductions in Brief Psychiatric Rating Scale ( BPRS ) total , BPRS agitation items , and Clinical Global Impressions-Severity scale scores were statistically significantly greater ( p < .05 , p < .01 , and p < .01 , respectively ) after ziprasidone i.m . treatment compared with haloperidol i.m . treatment . Further reductions in these scores also occurred in both groups following transition to oral treatment . Ziprasidone was associated with a lower incidence of movement disorders and a reduced requirement for anticholinergic medication during both i.m . and oral treatment compared with haloperidol .  Movement disorder scale scores improved with ziprasidone i.m . and oral treatment , but deteriorated with haloperidol . Other adverse events were rare with both treatments . CONCLUSION Ziprasidone i.m . was significantly more effective in reducing the symptoms of acute psychosis and was better tolerated than haloperidol i.m . , particularly in movement disorders . The transition from ziprasidone i.m . to oral ziprasidone was effective and well tolerated Kwentus J , Riesenberg RA , Mar and i M , Manning RA , Allen MH , Fishman RS , Spyker DA , Kehne JH , Cassella JV . Rapid acute treatment of agitation in patients with bipolar I disorder : a multicenter , r and omized , placebo‐controlled clinical trial with inhaled loxapine . Bipolar Disord 2012 : 14 : 31–40 . © 2012 The Authors . Journal compilation © 2012 John Wiley & Sons BACKGROUND While lithium is effective in treating the majority of bipolar patients during a manic episode , the addition of neuroleptic during the early phase of treatment has been common clinical practice in inpatient setting s. In an earlier open study , we demonstrated the utility of the short-acting benzodiazepine lorazepam as an adjunct to lithium for the clinical management of manic agitation . METHOD We now present data from a r and omized , double-blind clinical study of lorazepam versus haloperidol in 20 hospitalized patients with a DSM-III-R diagnosis of bipolar disorder who were being treated concomitantly with lithium .  Patients were rated using the Mania Rating Scale , Brief Psychiatric Rating Scale , Physician Global Impression Scale , and side effects scales . Data were analyzed using st and ard group comparisons and survival analysis . RESULTS There was no evidence for a significant difference between the two treatment groups in the magnitude of or time to response ( 5.0 + /- .82 days for haloperidol ; 6.5 + /- .93 days for lorazepam ) . Of the patients who were terminated from the protocol early , nonresponse was the primary reason in the lorazepam group while side effects were the reason in the haloperidol group . CONCLUSION Lorazepam may offer an efficacious and safe alternative to haloperidol as an adjunctive treatment to lithium in the clinical management of the early phase of manic agitation in a subgroup of bipolar patients Objective . To report efficacy and safety of transitioning patients receiving intramuscular ( IM ) formulations of aripiprazole or haloperidol to their respective oral formulations . Methods . 448 agitated patients with schizophrenia ( 73 % ) or schizoaffective disorder ( 27 % ) were r and omized to receive aripiprazole IM 9.75 mg , haloperidol IM 6.5 mg , or placebo IM within 24 hours . Patients treated with aripiprazole IM or haloperidol IM who completed this 24-hour IM phase were transitioned to the respective blinded oral formulations for 4 days ( aripiprazole 10 - 15 mg/day , n = 153 ; haloperidol 7.5 - 10 mg/day , n = 151 ) . Patients treated with placebo IM were transitioned to oral aripiprazole ( analysis not included ) . The primary efficacy measure was mean change in Positive and Negative Syndrome Scale-Excited Component ( PEC ) score from baseline of oral phase ( last value from 24-hour IM phase ) to endpoint ( study day 5 , last observation carried forward ) . Results . During the oral phase , aripiprazole 15 mg and haloperidol 10 mg were both effective in maintaining responses achieved on all efficacy measures during the 24-hour IM phase . Mean improvements in PEC scores from study day 1 to 5 were −1.37 for aripiprazole and −1.40 for haloperidol ( p = NS for aripiprazole versus haloperidol ) . Oral aripiprazole was well tolerated . Extrapyramidal symptom-related adverse events were lower for aripiprazole ( 1.3 % ) than haloperidol ( 8.0 % ) . Nausea and vomiting occurred more frequently in patients receiving aripiprazole ( 3.9 % and 2.6 % , respectively ) than in those receiving haloperidol ( 0.7 % and 1.3 % , respectively ) . Conclusions . Acutely agitated patients with schizophrenia or schizoaffective disorder treated with aripiprazole IM or haloperidol IM demonstrated similar effective and safe transition to their respective oral formulations . Initial benefits of reduced agitation and improved clinical status during the IM phase of the study were maintained throughout the oral phase of the study with good tolerability To investigate the efficacy and safety of intramuscular ( IM ) aripiprazole for the treatment of agitation in patients with bipolar I disorder , manic or mixed episodes . In total , 301 patients experiencing acute agitation were r and omized to IM aripiprazole 9.75 mg per injection ( n = 78 ) , IM aripiprazole 15 mg per injection ( n = 78 ) , IM lorazepam 2 mg per injection ( n = 70 ) , or IM placebo ( n = 75 ) in this double-blind multicenter study . Patients could receive up to 3 injections over 24 hours . Primary efficacy measure was mean change in Positive and Negative Syndrome Scale Excited Component score from baseline at 2 hours after first injection . Mean improvements in Positive and Negative Syndrome Scale Excited Component score at 2 hours were significantly greater with IM aripiprazole ( 9.75 mg , −8.7 ; 15 mg , −8.7 ) and IM lorazepam ( −9.6 ) versus IM placebo ( −5.8 ; P ≤ 0.001 ) . For all other efficacy measures , all 3 active treatments showed significantly greater improvements over IM placebo at 2 hours ( P < 0.05 ) , with similar improvements across the active treatments . Significant differences over IM placebo were seen by 45 to 60 minutes for several efficacy parameters . Both IM aripiprazole doses were well tolerated ; the safety profile was similar to oral aripiprazole . Oversedation ( Agitation-Calmness Evaluation Scale score of 8 or 9 ) during 2 hours after first injection was less frequent with IM aripiprazole 9.75 mg ( 6.7 % ) and IM placebo ( 6.8 % ) versus IM aripiprazole 15 mg ( 17.3 % ) and IM lorazepam ( 19.1 % ) . IM aripiprazole 9.75 and 15 mg are effective and well tolerated for acute agitation in bipolar disorder , although the low incidence of oversedation suggests a risk-benefit profile for IM aripiprazole 9.75 mg In a parallel groups , double-blind study , 54 acutely psychotic schizophrenics were given loxapine or haloperidol parenterally for 24 to 72 hours , then orally for a total study period of up to 10 days . Dosage ratios of loxapine to haloperidol ranged from a minimum of 2.7:1 to a maximum of 4.4:1 . Both groups showed significant and rapid improvement from baseline . Forty-eight percent of the loxapine patients and 33 % of the haloperidol patients achieved and maintained a global severity of illness rating of mild or better . By the end of the study , 84 % of the loxapine patients and 63 % of the haloperidol patients had achieved an improvement rating of moderate or marked . This difference approached significance ( p less than .10 ) . The most frequently reported adverse experiences were dystonic reactions and akathisia . The number and severity of adverse experiences did not differ significantly between drug groups . Intramuscular loxapine was at least as effective as haloperidol in the initial management of hostile and aggressive schizophrenic patients . The maintenance of therapeutic response after conversion to oral concentrate was comparable with the two drugs ABSTRACT Objective : To evaluate the efficacy and safety of quetiapine monotherapy for mania in bipolar disorder by an a priori defined combined analysis of data from two placebo-controlled studies . Method : The intent-to-treat ( ITT ) population s from two studies of patients with DSM-IV bipolar I disorder , manic episode , r and omised to 12 weeks of double-blind treatment with quetiapine ( up to 800 mg/day ) or placebo were combined . The primary efficacy endpoint was change in Young Mania Rating Scale ( YMRS ) score from baseline to Day 21 . Secondary endpoints included change from baseline in YMRS to Day 84 , YMRS response and remission rates and change from baseline to Days 21 and 84 in the Montgomery – Asberg Depression Rating Scale ( MADRS ) , Clinical Global Impressions ( CGI ) , Clinical Global Impressions – Bipolar ( CGI-BP ) and the Positive and Negative Syndrome Scale ( PANSS ) . These endpoints were analysed as continuous variables , using an analysis of covariance ( ANCOVA ) , with the baseline as covariate . In order to account for any difference in response between studies , the analyses were stratified by study as a fixed effect , and centre as a r and om effect . The Cochran – Mantel – Haenszel test was used to analyse binary variables . A chi square test was used to compare the frequency of adverse events between the treatment groups . Results : The combined analysis included a total of 403 patients from two quetiapine monotherapy studies in patients with bipolar I disorder . A significant improvement in YMRS score was observed from Day 4 ( p = 0.021 ) onward in the quetiapine group compared with placebo . The treatment advantage of quetiapine over placebo continued to increase to Day 21 ( p < 0.001 ) and Day 84 ( p < 0.001 ) . Significantly more quetiapine-treated than placebo-treated patients achieved a response ( p < 0.001 ) . The average quetiapine dose in responders was approximately 600 mg daily . Of adverse events occurring in ≥ 5 % of patients , quetiapine-treated patients had a significantly greater incidence versus placebo of somnolence ( 16.3 % vs. 4.0 % ) , dry mouth ( 15.8 % vs. 3 % ) , weight gain ( 9.1 % vs. 1.5 % ) and dizziness ( 6.7 % vs. 2.5 % ) . Conclusions : The data from this combined analysis support the results from the individual studies and indicate that quetiapine monotherapy is effective across a broad range of mood symptoms , fast-acting and well tolerated in the treatment of mania We report psychometric results of the  Behavioural Activity Rating Scale ( BARS ) using data from three Phase III clinical trials of intramuscular ziprasidone in acutely agitated patients with psychosis ( Studies 1 and 2 ) or in stable psychotic patients ( Study 3 ) . Convergent validity and divergent validity were assessed with baseline data from Studies 1 and 2 in subjects with acute agitation . To investigate convergent validity , we sought Pearson and Spearman correlation of BARS scores with scores on the Clinical Global Impression of Severity ( CGI-S ) Scale and a predefined cluster of agitation-related items from the Positive and Negative Syndrome Scale ( PANSS ) . For divergent validity , we sought Pearson and Spearman correlation between BARS scores and a predefined cluster of PANSS items measuring negative symptoms . Discriminant validity was investigated with the help of subjects with moderate psychopathology ( Study 3 ) . Wilcoxon rank-sum and two- sample t tests determined whether mean ( or median ) BARS scores differed between subjects with acute agitation ( Studies 1 and 2 ) and moderate psychopathology ( Study 3 ) . Responsiveness to treatment effect and rater reliability were also evaluated . In Study 2 , Pearson correlation coefficients of BARS scores with PANSS agitation items and CGI-S were moderate ( convergent validity ) and statistically significant ( P<0.005 ) . The correlation between BARS scores and PANSS negative component scores was low ( divergent validity ) . Treatment effect size was larger for BARS than for PANSS agitation items and CGI-S ( responsive to treatment differences ) . Virtually perfect inter- and intra-rater reliability was achieved . Study 1 produced similar results . BARS showed psychometrically valid properties for measurement of behavioral activity in acutely agitated patients with psychosis 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 In this double-blind study ,  haloperidol ( n = 15 ) and thiothixene ( n = 15 ) , administered parenterally in emergency rooms and outpatient facilities to 30 acutely excited , agitated psychotic patients in hourly doses of 4 mg . or 8 mg . , as needed over a four-hour period ( total dosage ranging from 4 to 32 mg . ) , achieved rapid tranquilization in 30 patients . Significant improvement was shown over a six-hour period on BPRS Total Score , the four factors -- Thinking Disorder , Anergic state , Excitement and Disorientation , and Depression and also on hourly ratings of 17 symptoms of a Psychiatric Target Symptom Profile . No significant differences were found between the haloperidol-treated and thiothixene-treated groups . Few adverse reactions were noted , all of them mild , the most frequent being drowsiness in six patients METHODS Patients ( n=302 ) with bipolar I disorder ( manic episode ) were r and omised to 12 weeks ' double-blind treatment with quetiapine ( flexibly dosed up to 800 mg/day ) , placebo , or haloperidol ( up to 8 mg/day ) . The primary efficacy outcome variable was change from baseline to Day 21 in Young Mania Rating Scale ( YMRS ) score . RESULTS YMRS score improved with quetiapine at Day 21 ( -12.29 versus -8.32 for placebo ; P<0.01 ) . The difference in favor of quetiapine increased by Day 84 ( -17.52 versus -9.48 ; P<0.001 ) . Haloperidol also showed an advantage over placebo at Days 21 and 84 ( P<0.001 ) . There was no significant difference in efficacy measures between quetiapine and haloperidol groups at any assessment except Day 21 . The only common adverse event with quetiapine was somnolence ( 12.7 % ) . Extrapyramidal symptoms ( EPS ) , including akathisia , occurred at 59.6 % with haloperidol , 12.7 % with quetiapine , 15.8 % with placebo . Most quetiapine responders ( 84 % ) received a dose of 400 - 800 mg/day . CONCLUSIONS Quetiapine was effective and well tolerated . The efficacy and tolerability profile of haloperidol ( including its propensity for EPS ) supported study validity OBJECTIVES Due to inherent dangers and barriers to research in emergency setting s , few data are available to guide clinicians about how best to manage behavioral emergencies . Key constructs such as agitation are poorly defined . This lack of empirical data led us to undertake a survey of expert opinion , results of which were published in the 2001 Expert Consensus Guidelines on the Treatment of Behavioral Emergencies . Several second-generation ( atypical ) antipsychotics ( SGAs ) are now available in new formulations for treating behavioral emergencies ( e.g. , intramuscular [ i.m . ] olanzapine and ziprasidone ; rapidly dissolving tablets of olanzapine and risperidone ) . Critical questions face the field . The SGAs are significantly different from the FGAs and from each other and have not been studied in unselected patients as were the FGAs . Can the SGAs can be thought of as a class , do all antipsychotics have similar anti-agitation effects in different conditions , and , if equally effective , what limits might their safety profiles impose ? Should antipsychotics be used more specifically to treat psychotic conditions , while benzodiazepines ( BNZs ) alone are used nonspecifically ? Few data are available concerning combinations of SGAs and BNZs , and findings concerning the traditional combination of haloperidol plus a BNZ may not be relevant to combinations with SGAs . The culture is also evolving with more emphasis on patient involvement in treatment decisions . An international consensus has been developing that calming rather than sedation is the appropriate endpoint of behavioral emergency interventions . We undertook a new survey of expert opinion to up date recommendations from the earlier survey . METHOD A written survey of 61 questions ( 1,020 options ) was mailed to 50 experts in the field , 48 ( 96 % ) of whom completed it . The survey sought to define level of agitation at which emergency interventions are appropriate , scope of assessment depending on urgency and patients ' ability to cooperate , guiding principles for selecting interventions , and appropriate physical and medication strategies at different levels of diagnostic confidence for a variety of provisional diagnoses and complicating conditions . A modified version of the R AND Corporation 's 9-point scale for rating appropriateness of medical decisions was used to score most options . Consensus was defined as a non-r and om distribution of scores by chi-square " goodness-of-fit " test . We assigned a categorical rank ( first line/preferred , second line/alternate , third line/usually inappropriate ) to each option based on the 95 % confidence interval around the mean . Ratings were used to develop guidelines for preferred strategies in key clinical situations . This study received financial support from multiple sponsors , with the panel kept blind to sponsorship to reduce possible bias . Medication ratings were based on responses of only those respondents with direct experience with each drug . In reporting practice patterns , the panel was asked to respond based on actual data rather than estimates . RESULTS The expert panel reached consensus on 78 % of the options rated on the 9-point scale . The responses suggest that physicians can make provisional diagnoses with some confidence and that pharmacological and nonpharmacological interventions are selected differentially based on diagnosis and other salient demographic and medical features . BNZs are recommended when no data are available , when there is no specific treatment ( e.g. , personality disorder ) , or when they may have specific benefits ( e.g. , intoxication ) . No single SGA emerges as a nonspecific replacement for haloperidol ; instead , different SGAs are preferred in various circumstances consistent with current evidence . To the degree that haloperidol is recommended , it is almost always in combination with a BNZ ; haloperidol alone is preferred only in the medically compromised . In contrast , the SGAs are more often recommended for use alone , and the panel would avoid combining BNZs with some SGAs . Oral risperidone alone or combined with a BNZ receives strong support in a variety of situations . Oral olanzapine was rated very similarly to risperidone , with slightly higher ratings than risperidone in situations where it has been studied ( e.g. , schizophrenia , mania ) and slightly lower ratings where it has not been studied or safety may be a concern ; there was less support for combining oral olanzapine with a BNZ . For oral treatment of agitation related to schizophrenia or mania , olanzapine alone , risperidone alone or combined with a BNZ , and haloperidol plus a BNZ are first line , with strong support also for combining divalproex with the antipsychotic for presumed mania . Oral ziprasidone and quetiapine generally received similar second-line ratings in most situations . If a parenteral agent is needed , i.m . olanzapine alone received somewhat more support than i.m . ziprasidone alone ; however , there was more support for i.m . ziprasidone alone or combined with a BNZ than for i.m . olanzapine plus a BNZ , probably reflecting safety concerns . For example , for a provisional diagnosis of schizophrenia , first-line parenteral options are i.m . olanzapine or ziprasidone alone or i.m . haloperidol or ziprasidone combined with a BNZ . Neither of the new parenteral formulations received as much support as traditional agents ( i.m . BNZs , i.m . haloperidol ) when no data are available or the diagnosis involves medical comorbidity or intoxication . When initial intervention with risperidone , ziprasidone , or haloperidol is unsuccessful , the panel recommended adding a BZD to the antipsychotic . However , when initial treatment with olanzapine or quetiapine is unsuccessful , increasing the dosage is recommended . Perphenazine was consistently rated second line and droperidol and chlorpromazine received third-line ratings throughout . CONCLUSIONS Within the limits of expert opinion and with the expectation that future research data will take precedence , these guidelines suggest that the SGAs are now preferred for agitation in the setting of primary psychiatric illnesses but that BNZs are preferred in other situations INTRODUCTION A transition from IM to oral formulation of an antipsychotic agent is often required during the long-term management of schizophrenia . This multicenter trial evaluates the IM/oral sequential administration of ziprasidone in agitated subjects with an exacerbation of schizophrenia . METHODS Adult patients requiring IM therapy for schizophrenic symptoms were assigned to IM ziprasidone 10 mg for 3 days , followed by oral ziprasidone ( initial dose : 80 mg/day ) for 8 weeks . The primary efficacy outcomes were the change in the total PANSS and in the CGI-S scores vs. baseline values . RESULTS In total , 150 patients were included in the study . A decline in the PANSS and CGI-S scores was observed throughout the study ( p < 0.0001 vs. baseline ) : these reductions became significant at the point of transition from IM to oral formulation ( p < 0.0001 vs. baseline ) . DISCUSSION Even with the limitations of any non-comparative study , these results suggest that the IM/oral sequential administration of ziprasidone is an effective and well tolerated therapeutic option in the management of acute exacerbations of schizophrenia in agitated patients In a double-blind clinical study , 27 acutely agitated patients were treated with an intramuscular injection of 5 mg of droperidol or 5 mg of haloperidol from identical appearing vials . At 30 minutes following treatment , 81 % of the patients treated with haloperidol but only 36 % treated with droperidol required a second injection ( p less than .05 ) . Thus , droperidol , a safe butyrophenone neuroleptic , appears to be a drug of choice for rapid and reliable control of acute agitation OBJECTIVE This study was a comparative investigation of the clinical efficacy and safety of intramuscular ( IM ) olanzapine , IM haloperidol , and IM levomepromazine in acute agitated patients with schizophrenia . METHODS The subjects were 122 in patients . Their clinical symptoms were assessed using Positive and Negative Syndrome Scale Excited Component ( PANSS-EC ) , PANSS , and Agitation-Calmness Evaluation Scale , and their safety were assessed using the Abnormal Involuntary Movement Scale , Barnes Akathisia Rating Scale ( BARS ) , and Drug-induced Extrapyramidal Symptoms Scale ( DIEPSS ) . RESULTS The mean changes from baseline on the PANSS-EC , Agitation-Calmness Evaluation Scale , Abnormal Involuntary Movement Scale , BARS , and DIEPSS scores were significantly better in both IM olanzapine and IM levomepromazine than in IM haloperidol . Of these , the mean changes from baseline on the BARS and DIEPSS scores were significantly better in IM olanzapine than in IM levomepromazine . The mean change from baseline on the PANSS positive score was significantly better in both IM olanzapine and IM haloperidol than in IM levomepromazine . CONCLUSIONS The results of this study suggest the possibility that the anti-agitation effects of IM olanzapine and IM levomepromazine are more rapid than those of IM haloperidol . No worsening of EPS was observed . Our results also suggest that compared with IM levomepromazine , IM olanzapine is safer and affords greater improvement in symptoms OBJECTIVE The authors conducted a r and omized , placebo-controlled study of nicotine replacement therapy for the reduction of agitation and aggression in smokers with schizophrenia . METHOD Participants were 40 smokers 18 - 65 years of age admitted to a psychiatric emergency service with a diagnosis of schizophrenia confirmed by the Mini International Neuropsychiatric Interview . Patients were screened for agitation with the excited component subscale of the Positive and Negative Syndrome Scale ( PANSS ) and for nicotine dependence with the Fagerström Test for Nicotine Dependence . A score of at least 14 on the PANSS excited component subscale and at least 6 on the Fagerström test were required for study eligibility . Participants in the nicotine replacement group received a 21-mg nicotine transdermal patch , and those in the placebo group were treated with a placebo patch . Participants received usual care with antipsychotics . The Agitated Behavior Scale and other agitation measures were administered at baseline and again at 4 and 24 hours . RESULTS At baseline , participants were at least moderately agitated , and 28 % reported aggressive behavior in the previous week . The mean Agitated Behavior Scale score for the nicotine replacement group was 33 % lower at 4 hours and 23 % lower at 24 hours than for the placebo group . Participants with lower levels of nicotine dependence responded better than those with higher levels of dependence . CONCLUSIONS The drug-placebo difference in this study was similar to that obtained in trials of parenteral antipsychotics in similar population s. This finding suggests that in patients with schizophrenia , smoking status should be included in the assessment of agitation and nicotine replacement included in the treatment of those who are smokers
target: For its management , experts agreed in considering  verbal de-escalation  and  environmental modification techniques  as first choice , considering physical restraint as a last resort strategy .
background: BACKGROUND Psychomotor agitation is associated with different psychiatric conditions and represents an important issue in psychiatry .
  Current recommendations on agitation in psychiatry are not univocal .
  Actually , an improper assessment and management may result in unnecessary coercive or sedative treatments .
  A thorough and balanced review plus an expert consensus can guide assessment and treatment decisions .