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 *
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
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 .