Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine Rapid tranquilization for agitated patients in emergency psychiatric rooms: a randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone. Rapid Tranquilization of Severely Agitated Patients With Schizophrenia Spectrum Disorders: A Naturalistic, Rater-Blinded, Randomized, Controlled Study With Oral Haloperidol, Risperidone, and Olanzapine Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study. Efficacy of lorazepam and haloperidol for rapid tranquilization in a psychiatric emergency room setting A double-blind randomized clinical trial of rapid tranquilization with I.M. clonazepam and I.M. haloperidol in agitated psychotic patients with manic symptoms. Rapid tranquillisation in psychiatric emergency settings in India: pragmatic randomised controlled trial of intramuscular olanzapine versus intramuscular haloperidol plus promethazine Rapid tranquillisation in psychiatric emergency settings in Brazil: pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting. Pragmatic randomised trial of intramuscular lorazepam v. haloperidol plus promethazine. The use of midazolam in acutely agitated psychiatric patients. Relative efficacy of parenteral haloperidol and thiothixene for the emergency treatment of acutely excited and agitated patients. Propericiazine in Psychiatric Emergencies: A controlled comparative study * Current practices in managing acutely disturbed patients at three hospitals in Rio de Janeiro-Brazil: a prevalence study Are Low Doses of Antipsychotics Effective in the Management of Psychomotor Agitation? A Randomized, Rated-Blind Trial of 4 Intramuscular Interventions Physical restraints versus seclusion room for management of people with acute aggression or agitation due to psychotic illness (TREC-SAVE): a randomized trial. Rapid tranquilization: the efficacy of oral concentrate. Varenicline, smoking cessation, and neuropsychiatric adverse events. Rapid tranquilization: A comparative study of thiothixene and haloperidol Efficacy of Topiramate, Valproate, and Their Combination on Aggression/Agitation Behavior in Patients With Psychosis Does psychomotor agitation in major depressive episodes indicate bipolarity? Memantine for agitation/aggression and psychosis in moderately severe to severe Alzheimer's disease: a pooled analysis of 3 studies. Efficacy and tolerability of carbamazepine for agitation and aggression in dementia. Effectiveness of Rapid Initial Dose Escalation of up to Forty Milligrams per Day of Oral Olanzapine in Acute Agitation
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 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 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 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 The efficacy of a benzodiazepine was compared with that of a neuroleptic for the rapid tranquilization of patients presenting at a psychiatric emergency room service . Thirty-seven highly agitated patients exhibiting psychotic symptoms were r and omly assigned to receive either 2 mg lorazepam or 5 mg haloperidol as needed every 30 min for 4 h. Administration route was either intramuscular injection or oral concentrate . Symptom ratings were conducted each hour using double-blind procedures . Both medications reduced symptom ratings on the Brief Psychiatric Rating Scale and Global Clinical Impression of Overall Symptom Severity Scale . Global Clinical Impression scores for the two medication groups did not differ significantly either at baseline or at 4 h after entry into the study . However , Global Clinical Impression scores of patients in the lorazepam group were less severe at intermittent ratings . The groups did not differ on the Brief Psychiatric Rating Scale at any rating time . No differences were found either in the number of doses administered or in the administration route selected . Given the potential for severe extrapyramidal symptoms developing hours or days after a single dose of haloperidol , lorazepam may provide an excellent alternative for the rapid tranquilization of the acutely agitated psychotic patient in the emergency room setting 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 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 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 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 Agents currently used for acutely agitated patients such as sodium amytal and haloperidol are disadvantageous because of their adverse effects on the respiratory and extrapyramidal systems . Because of this , a rapid , safe , well-absorbed agent such as midazolam would be useful . This study compares the effectiveness of midazolam , sodium amytal , and haloperidol in agitated schizophrenic patients . Five male patients between 28 and 59 years were r and omly assigned to each group . They were administered intramuscularly either 10 mg of haloperidol , 250 mg of sodium amytal , or 5 mg of midazolam . Over a 2-hour period , patients were rated for motor agitation , hostility , auditory hallucinations , and flight of ideas . Both midazolam and sodium amytal were significantly more effective than haloperidol in controlling motor agitation . There were no treatment differences on any other symptom rated . These results indicate that further studies on the use of midazolam to achieve rapid tranquilization would be useful 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 Its pharmacological action in animals is similar to that of the major tranquillizers . It has a five times more potent cataleptic action than prochlorperazine , seventeen times more potent antiemetic activity and four times more potent antiserotonin activity than chlorpromazine . In clinical studies propericiazine has been found to be an effective antipsychotic medication ( 1,3,4,6,7 ) . Furthermore , it was noted that the drug had particular usefulness in the treatment of character disorders ( 6 ) and in patients manifesting aggressive behaviour ( 2,5 ) . In a previous study propericiazine was tested for its calming effect when given as PRN ( prorenata ) medication to agitated hospitalized psychiatric patients under treatment with various other psychiatric drugs . The drug had a calming effect in forty-four of the fifty cases ( 7 ) . To further substantiate these findings in this study the efficacy and side effects of propericiazine were compared with Background The medical management of aggressive and violent behaviour is a critical situation for which there is little evidence . In order to prepare for a r and omised trial , due to start in the psychiatric emergency rooms of Rio de Janeiro in 2001 , a survey of current practice was necessary . Methods A seven day survey of pharmacological management of aggressive people with psychosis in the emergency rooms of all four public psychiatric hospitals in Rio de Janeiro , Brazil . Results In one hospital data were not available . Of the 764 people with psychosis attending these ERs , 74 were given IM medication for rapid tranquillisation ( 9.7 % , 2.1/week/100,000 ) . A haloperidol-promethazine mix ( with or without other drugs ) was used for the majority of patients ( 83 % ) . Conclusion The haloperidol-promethazine mix , given intramuscularly for rapid tranquilization , is prevalent in Rio , where it is considered both safe and efficient . However , scientific evaluation of all pharmacological approaches to rapid tranquilization of psychotic people is inadequate or incomplete and a r and omized trial of IM haloperidol-promethazine is overdue 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 After de-escalation techniques have failed , restraints , seclusion and /or rapid tranquillization may be used for people whose aggression is due to psychosis . Most coercive acts of health care have not been evaluated in trials . METHOD People admitted to the emergency room of Instituto Philippe Pinel , Rio de Janeiro , Brazil , whose aggression/agitation was thought due to psychosis and for whom staff were unsure if best to restrict using physical restraints or a seclusion room  , were r and omly allocated to one or the other and followed up to 14 days . The primary outcomes were ' no need to change intervention early - within 1 h ' and ' not restricted by 4 h ' . RESULTS A total of 105 people were r and omized . Two-thirds of the people secluded were able to be fully managed in this way . Even taking into account the move out of seclusion into restraints , this study provides evidence that embarking on the less restrictive care pathway ( seclusion ) does not increase overall time in restriction of some sort [ not restricted by 4 h : relative risk 1.09 , 95 % confidence interval 0.75 - 1.58 ; mean time to release : restraints 337.6 ( s.d.=298.2 ) min , seclusion room 316.3 ( s.d.=264.5 ) min , p=0.48 ] . Participants tended to be more satisfied with their care in the seclusion group ( 17.0 % v. 11.1 % ) but this did not reach conventional levels of statistical significance ( p=0.42 ) . CONCLUSIONS This study should be replicated , but suggests that opting for the least restrictive option in circumstances where there is clinical doubt does not harm or prolong coercion The efficacy of oral concentrate in the rapid tranquilization of 159 acutely disturbed patients in a psychiatric emergency service was evaluated . Patients were r and omly assigned to 1 of 10 treatment groups : 7 oral groups and 3 comparison intramuscular groups . Although intramuscular medication produced a faster response , concentrate also proved to be effective for rapid tranquilization . Side effects were benign and minimal . Age , sex , race , and diagnosis had no effect on outcome . The use of concentrate as a paradigm for treating acutely psychotic patients is discussed OBJECTIVE In 2009 , the U.S. Food and Drug Administration issued a black box warning for varenicline regarding neuropsychiatric events . The authors used data from r and omized controlled trials and from a large Department of Defense ( DOD ) observational study to assess the efficacy and safety of varenicline . METHOD The authors reanalyzed data from the 17 placebo-controlled r and omized controlled trials ( N=8,027 ) of varenicline conducted by Pfizer , using complete intent-to-treat person-level longitudinal data to assess smoking abstinence and reports of suicidal thoughts and behavior , depression , aggression/agitation , and nausea and to compare effects in patients with ( N=1,004 ) and without ( N=7,023 ) psychiatric disorders . The authors also analyzed a large DOD data set to compare acute ( 30-day and 60-day ) rates of neuropsychiatric adverse events in patients receiving varenicline or nicotine replacement therapy ( N=35,800 ) and to assess reports of anxiety , mood , and psychotic symptoms and disorders , other mental disorders , and suicide attempt . RESULTS In the r and omized controlled trials , varenicline increased the risk of nausea ( odds ratio=3.69 , 95 % CI=3.03 - 4.48 ) but not rates of suicidal events , depression , or aggression/agitation . It significantly increased the abstinence rate , by 124 % compared with placebo and 22 % compared with bupropion . Having a current or past psychiatric illness increased the risk of neuropsychiatric events equally in treated and placebo patients . In the DOD study , after propensity score matching , the overall rate of neuropsychiatric disorders was significantly lower for varenicline than for nicotine replacement therapy ( 2.28 % compared with 3.16 % ) . CONCLUSIONS This analysis revealed no evidence that varenicline is associated with adverse neuropsychiatric events . The evidence supports the superior efficacy of varenicline relative to both placebo and bupropion , indicating considerable benefit without evidence of risk of serious neuropsychiatric adverse events , in individuals with and without a recent history of a psychiatric disorder In a double-blind comparative clinical study , both thiothixene and haloperidol were found to be effective agents for rapid tranquilization of manic and schizophrenic patients . While no statistically significant difference in any of the psychopathological areas which may create a psychiatric emergency was found , results of this study provide further substantiation of the notion that thiothixene has favorable effects on anergia Abstract : Topiramate is an antiepileptic drug , recently also used in the treatment of psychiatric diseases . Inasmuch as topiramate and valproate , which are currently used for aggressive behavior , share several pharmacological mechanisms ( positive modulatory effect on the GABA activity and negative modulatory effect on glutamatergic neurotransmission ) , the objective of the present study was to compare the pharmacological effects of topiramate with those of valproate and their combination in patients with psychiatric disorders showing marked aggression and agitation . A retrospective , case-controlled , mirror-image study was carried out in a sample of 45 in patients affected by schizophrenia , schizoaffective and bipolar disorder , and hospitalized in a maximum-security Canadian psychiatry hospital .  Overt Aggression Scale , Agitation-Calmness Evaluation Scale , number and intensity of psychotic episodes , number of episodes of withdrawal from group activities per week , and number of therapeutic isolation per week and of strict surveillance intervention per week were evaluated before and after the treatments . Results indicate that patients treated with topiramate show a decrease in the average score of the Overt Aggression Scale , a decrease of episodes of agitation and of strict surveillance interventions . This effect was similar to the group treated with valproate or with the combination of valproate-topiramate . However , valproate therapy , but not topiramate therapy , decreased the intensity of agitation episodes measured by the Agitation-Calmness Evaluation Scale ;  valproate and the combination topiramate-valproate decreased the number of psychotic disorganization episodes as well . These results suggest that topiramate could be a valid medicine in the control of aggression in psychosis . Double-blind , r and omized , placebo-controlled studies need to further assess this pharmacological indication 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 Long-st and ing evidence indicates that Alzheimer 's disease patients with behavioral symptoms have a worse prognosis and a more rapid disease progression . The current retrospective analysis evaluated the efficacy and safety of memantine in a sub population of patients with Alzheimer 's disease exhibiting behavioral symptoms of agitation/aggression or psychosis at baseline . METHOD A pooled analysis was conducted in people with agitation/aggression or psychosis from 3 large 6-month , r and omized studies in moderately severe to severe Alzheimer 's disease . The effect of memantine and placebo on these specific symptoms was evaluated using the Neuropsychiatric Inventory ( NPI ) subitem cluster of agitation and psychosis . Outcomes on global , cognitive , and functional measures were also analyzed . RESULTS Sixty percent of the total patient group had baseline symptoms of agitation/aggression , delusions , or hallucinations on the NPI . At both 12 and 24/28 weeks , there was a significant treatment advantage for memantine over placebo for the proportion of patients showing improvement on the defined neuropsychiatric symptom cluster ( 55.6 % vs. 44.4 % at week 12 , p = .008 ; 58.0 % vs. 44.8 % at week 24/28 , p = .002 ) and specifically for the treatment of agitation/aggression ( 55.3 % vs. 43.1 % at week 12 , p = .011 ; 61.0 % vs. 45.0 % at week 24/28 , p < .001 ) . Placebo-treated patients in this population demonstrated an accelerated disease progression for global ( Clinician 's Interview-Based Impression of Change Plus Caregiver Input ) , cognitive ( Severe Impairment Battery ) , and functional ( Alzheimer Disease Cooperative Study Activities of Daily Living Inventory 19-item scale ) outcomes , but memantine conferred statistically significant benefit for all measures . Tolerability in this population remained good , and fewer memantine-treated patients than placebo-treated patients withdrew due to adverse events . CONCLUSIONS This post hoc analysis provides important evidence from placebo-controlled trials that memantine may be a safe and effective treatment in Alzheimer 's disease patients with agitation/aggression or psychosis , who are otherwise prone to rapid progression . Memantine treatment provided benefits in cognitive , functional , and global outcomes in these patients and for their agitation/aggression OBJECTIVE The efficacy , safety , and tolerability of carbamazepine in the treatment of agitation and aggression associated with dementia were assessed . METHOD In a 6-week , r and omized , multisite , parallel-group study of 51 nursing home patients with agitation and dementia , individualized doses of carbamazepine were compared with placebo . Except for a physician monitor and a pharmacist , all participants were blind to treatment . The primary outcome measures were the Brief Psychiatric Rating Scale ( BPRS ) and Clinical Global Impression ( CGI ) global improvement rating . Secondary measures included measures of behavior , aggression , cognition , functional status , staff time , safety , and tolerability . Intent-to-treat analysis was performed . RESULTS The modal carbamazepine dose at 6 weeks was 300 mg/day , and a mean serum level of 5.3 micrograms/ml was achieved . The study was terminated after a planned interim analysis showed that carbamazepine provided more benefit than did placebo . Over 6 weeks the mean total BPRS score decreased 7.7 points for the carbamazepine group and 0.9 for the placebo group , and the weekly scores showed a gradual divergence between the two groups . CGI ratings showed global improvement in 77 % of the patients taking carbamazepine and 21 % of those taking placebo . Secondary analyses confirmed that the positive changes were due to decreased agitation and aggression . The drug was generally well tolerated , and no change in cognition or functional status occurred . The perception of staff time needed to manage agitation showed a decrease for carbamazepine but not placebo . CONCLUSIONS This controlled study showed significant short-term efficacy of carbamazepine for agitation with generally good safety and tolerability 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
The association of haloperidol with promethazine ( H + P ) promoted tranquilization and presented better safety profile , with moderate quality evidence .
Olanzapine demonstrated benefit towards tranquilization and good safety profile , but needed additional administration to keep tranquilization .
There was no benefit in the use of haloperidol alone or associated to another psychotropic to most outcomes evaluated .
Rapid tranquilization is an intervention used in control of agitation or aggression in patients with mental disorders .
This study synthesized the available evidence regarding efficacy and safety of drugs used for rapid tranquilization in psychiatric patients with psychomotor agitation .