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4. Il paziente agitato o aggressivo
2014 Il Pensiero Scientifico Editore Question: Should haloperidol vs chlorpromazine be used in adults with aggression or agitation?
Bibliography: Leucht C, Kitzmantel M, Kane J, Leucht S, Chua WLLC. Haloperidol versus chlorpromazine for schizophrenia. Cochrane Database of Systematic Reviews 2008, Issue 1.
Quality assessment
No of patients
Quality Importance
Relative
Risk of bias Inconsistency
Indirectness Imprecision
Haloperidol Chlorpromazine
Absolute
Global state: No clinically significant improvement - as defined by the individual studies
randomised no serious 165 fewer per 1000 ⊕⊕ΟΟ CRITICAL (from 302 fewer to 90 Leaving the study early
randomised no serious very serious5 none RR 0.66 (0.1 8 fewer per 1000 (from ⊕⊕ΟΟ CRITICAL 21 fewer to 76 more) Extrapyramidal symptoms
randomised no serious RR 3.49 (0.84 111 more per 1000 (from ⊕⊕ΟΟ IMPORTANT 7 fewer to 597 more) randomised no serious very serious3 none 112 fewer per 1000 ⊕⊕ΟΟ IMPORTANT (from 160 fewer to 73 1 From Analysis 2.2 of Leucht 2008. Haloperidol dosages: 5mg (2 studies); 1-5mg (1 study); 5-30mg (1 study). Chlorpromazine dosages: 25mg (1 study); 50mg (2 studies); 25-300mg (1 study). 2 Visual inspection of forest plot suggests some heterogeneity. I-squared=58% 3 Less than 200 patients included in the analysis, and CI ranges from substantial benefit with haloperidol to no benefit at all. 4 From Analysis 2.1 of Leucht 2008 5 Less than 200 patients included in the analysis, and CI ranges from substantial benefit with haloperidol to substantial benefit with chlorpromazine. 6 From Analysis 2.6 of Leucht 2008 7 Less than 200 patients included in the analysis, and CI ranges from substantial benefit with chlorpromazine to no benefit at all. 8 From Analysis 2.4 of Leucht 2008 2014 Il Pensiero Scientifico Editore Question: Should clotiapine vs conventional antipsychotics be used in adults with aggression or agitation?
Bibliography: Berk M, Rathbone J, Mandriota-Carpenter SL. Clotiapine for acute psychotic illnesses. Cochrane Database of Systematic Reviews 2004, Issue 4.
Quality assessment
No of patients
Quality Importance
Relative
Risk of bias Inconsistency Indirectness Imprecision
Clotiapine
Absolute
Global state: No clinically significant improvement - as defined by the individual studies
randomised no serious RR 0.82 (0.25 63 fewer per 1000 (from ⊕ΟΟΟ CRITICAL 262 fewer to 579 more) Leaving the study early
randomised no serious RR 2.26 (0.4 102 more per 1000 (from ⊕ΟΟΟ CRITICAL 48 fewer to 958 more) 1 From Analysis 1.1 of Berk 2004. Clotiapine dose: 40-240mg/day 2 Visual inspection of forest plot suggests significant heterogeneity. I-squared=55% 3 Only one study used clotiapine injections. 4 Less than 100 patients in the analysis, and CI ranges from substantial benefit with clotiapine to substantial benefit with conventional antipsychotics. 5 From Analysis 1.3 of Berk 2004 6 Less than 200 patients in the analysis, and CI ranges from substantial benefit with clotiapine to substantial benefit with conventional antipsychotics. 2014 Il Pensiero Scientifico Editore Question: Should clotiapine vs lorazepam be used in adults with aggression or agitation?
Bibliography: Berk M, Rathbone J, Mandriota-Carpenter SL. Clotiapine for acute psychotic illnesses. Cochrane Database of Systematic Reviews 2004, Issue 4.
Quality assessment
No of patients
Quality Importance
Relative
Risk of bias
Indirectness Imprecision
Clotiapine Lorazepam
Absolute
Global state: No clinically significant improvement - as defined by the individual studies (Better indicated by lower values)
no serious risk no serious MD 3.36 lower (8.09 lower to ⊕ΟΟΟ Leaving the study early
no serious risk no serious RR 1 (0.07 to 0 fewer per 1000 (from 31 ⊕ΟΟΟ CRITICAL fewer to 475 more) 1 From Analysis 2.1 of Berk 2004 2 Only one study into this analysis. 3 Outcome measured three days after beginning of treatment 4 Less than 100 patients in the analysis, and CI ranges from substantial benefit with clotiapine to no benefit at all. 5 From Analysis 2.2 of Berk 2004 6 Less than 100 patients in the analysis, and CI ranges from substantial benefit with clotiapine to sbstantial benefit with lorazepam. 2014 Il Pensiero Scientifico Editore Question: Should zuclopenthixol vs haloperidol be used in adults with aggression or agitation?
Bibliography: Gibson RC, Fenton M, da Silva Freire Coutinho E, Campbell C. Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses. Cochrane Database of Systematic
Reviews 2004, Issue 3.
Quality assessment
No of patients
Importance
Relative
Risk of bias Inconsistency
Indirectness Imprecision
Zuclopenthixol Haloperidol
Absolute
Global state: Requiring supplementary medication
randomised no serious 158 more per 1000 (0.97 to 2.3) (from 10 fewer to 420 Leaving the study early
randomised no serious 4 fewer per 1000 (from risk of bias inconsistency (0.31 to 2.31) 20 fewer to 38 more) Extrapyramidal symptoms: dystonia
randomised no serious 44 fewer per 1000 ⊕⊕⊕Ο IMPORTANT risk of bias inconsistency (0.34 to 1.36) (from 90 fewer to 49 MODERATE 1 From Analysis 1.2 of Gibson 2004 2 Visual inspection of forest plot suggests significant heterogeneity. I-squared=79% 3 Less than 200 patients in the analysis. CI ranges from substantial benefit for haloperidol to no difference between haloperidol and zuclopenthixol. 4 From Analysis 1.12 of Gibson 2004. In one study zuclopenthixol was compared with chlorpromazine. 5 Very low total number of events in both treatment arms. CI ranges from substantial benefit with zuclopenthixol to substantial benefit with haloperidol. 6 From Analysis 1.9 of Gibson 2004 7 Less than 200 patients in the analysis. CI ranges from substantial benefit for zuclopenthixol to no difference between haloperidol and zuclopenthixol. 2014 Il Pensiero Scientifico Editore Question: Should benzodiazepines vs antipsychotics be used in adults with aggression or agitation?
Bibliography: Gillies D, Beck A,McCloud A, Rathbone J. Benzodiazepines for psychosis-induced aggression or agitation. Cochrane Database of Systematic Reviews 2005, Issue 4.
Quality assessment
No of patients
Importance
Relative
Imprecision
Benzodiazepines Antipsychotics
Absolute
Global state: Sedation - medium term
randomised no serious no serious 46 fewer per 1000 risk of bias inconsistency (from 101 fewer to MODERATE Extrapyramidal symptoms
randomised no serious no serious 113 fewer per 1000 ⊕⊕⊕⊕ IMPORTANT risk of bias inconsistency (from 78 fewer to 1 From Analysis 2.2 of Gillies 2005. Haloperidol (5-10mg im) in all studies but one (olanzapine 10-25mg). Lorazepam 2-5mg in three studies, diazepam, flunitrazepam and clonazepam in one study each. 2 CI ranges from substantial benefit of antipsychotics to no difference between benzodiazepines and antipsychotics. 3 From Analysis 2.16 of Gillies 2005 2014 Il Pensiero Scientifico Editore Question: Should benzodiazepines plus antipsychotics vs benzodiazepines be used in adults with aggression or agitation?
Bibliography: Gillies D, Beck A,McCloud A, Rathbone J. Benzodiazepines for psychosis-induced aggression or agitation. Cochrane Database of Systematic Reviews 2005, Issue 4.
Quality assessment
No of patients
Quality Importance
Benzodiazepines plus
Relative
Indirectness Imprecision
Absolute
Global state: Need for additional medication - medium term
randomised no serious no serious 12 more per 1000 ⊕⊕ΟΟ CRITICAL risk of bias inconsistency (from 130 fewer to 1 From Analysis 3.1 of Gillies 2005 2 Less than 100 patients in the analysis. CI ranges from substantial benefit of the combination to substantial benefit of benzodiazepines alone. 2014 Il Pensiero Scientifico Editore Question: Should benzodiazepines plus antipsychotics vs antipsychotics be used in adults with aggression or agitation?
Bibliography: Gillies D, Beck A,McCloud A, Rathbone J. Benzodiazepines for psychosis-induced aggression or agitation. Cochrane Database of Systematic Reviews 2005, Issue 4.
Quality assessment
No of patients
Importance
Benzodiazepines plus
Relative
Indirectness Imprecision
Absolute
Global state: Need for additional medication - medium term
randomised no serious no serious 44 fewer per 1000 risk of bias inconsistency2 (from 186 fewer to Extrapyramidal symptoms
randomised no serious no serious RR 0.45 180 fewer per 1000 ⊕⊕⊕Ο IMPORTANT risk of bias inconsistency (from 20 fewer to MODERATE 1 From Analysis 4.1 of Gillies 2005 2 Only one study in this analysis 3 Less than 100 patients in the analysis. CI ranges from benefit of the combination to benefit of antipsychotics alone. 4 From Analysis 4.6 of Gillies 2005 5 Less than 100 patients in the analysis 2014 Il Pensiero Scientifico Editore Question: Should midazolam vs propofol be used in adults with aggression or agitation?1,2
Bibliography: Hohl et al. Safety and Clinical Effectiveness of Midazolam versus Propofol for Procedural Sedation in the Emergency Department: A Systematic Review Academic Emergency Medicine
2008; 15:1–8. Nobay F, Simon BC, Levitt MA, Dresden GM. A prospective, double-blind, randomized trial of midazolam versus haloperidol versus lorazepam in the chemical restraint of violent and
severely agitated patients. Academy of Emergency Medicine 2004;11: 744-9. Isbister GK, Calver LA, Page CB, Stokes B, Bryant JL, Downes MA. Randomized controlled trial of intramuscular droperidol
versus midazolam for violence and acute behavioral disturbance: the DORM study. Annals of Emergency Medicine 2010; 56: 392-401.
Quality assessment
No of patients
Importance
Relative
Risk of bias
Imprecision
Midazolam Propofol
Absolute
Efficacy: procedural sedation
no serious risk of 1 There is also one additional RCT comparing midazolam with haloperidol and lorazepam (Nobay 2004). 27 patients received lorazepam, 42 patients received haloperidol, and 42 patients received midazolam. The mean (SD) time to sedation was 32.2 (SD 20) minutes for patients receiving lorazepam, 28.3 (SD 25) minutes for haloperidol, and 18.3 (SD 14) minutes for midazolam. 2 There is also a RCT (Isbister 2010) comparing midazolam with droperidol and the combination. From 223 emergency department 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. 3 From Hohl 2008. 4 RCTs, 232 patients. 4 The study population is different from our study population. In this review included patients who received procedural sedation (PS) for orthopedic reductions, cardioversion and chest tube insertions. Additionally, midazolam was given IV and not IM. Finally, the comparison group received propofol, an agent not used for psychiatric indications. 5 Efficacy of midazolam: 89.9% (95% CI = 83.2% to 94.6%). Efficacy of propofol: 92.8% (95% CI = 87.5% to 96.8%) 2014 Il Pensiero Scientifico Editore Question: Should haloperidol plus promethazine vs lorazepam be used in adults with aggression or agitation?1
Bibliography: Huf G, Alexander J, AllenMH, Raveendran NS.Haloperidol plus promethazine for psychosis-induced aggression. Cochrane Database of Systematic Reviews 2009, Issue 3.
Quality assessment
No of patients
Importance
Haloperidol plus
Relative
Imprecision
Lorazepam
Absolute
Efficacy: NOT tranquil or asleep by 30 minutes
randomised no serious no serious 19/100 RR 0.26 (0.1 141 fewer per 1000 risk of bias inconsistency3 (from 61 fewer to 171 Efficacy: NOT asleep
randomised no serious no serious 468 fewer per 1000 risk of bias inconsistency3 (0.29 to 0.54) (from 359 fewer to Serious adverse effects
randomised no serious no serious 7 fewer per 1000 risk of bias inconsistency3 (0.01 to 8.09) (from 10 fewer to 71 MODERATE Extrapyramidal side-effects
randomised no serious no serious ⊕⊕⊕⊕ IMPORTANT risk of bias inconsistency3 1 Haloperidol IM: dose up to 10 mg + promethazine IM: dose up to 50 mg. Lorazepam IM: dose up to 4 mg. 2 From Analysis 1.1 of Huf 2009 3 Only one study included in this analysis 4 Time until tranquil or asleep: haloperiol plus promethazine: 29.7 (35.6) minutes. Lorazepam: 47.8 (46.7). 5 From Analysis 1.3 of Huf 2009 6 From Analysis 1.5 of Huf 2009 7 CI ranges from substantial benefit with haloperidol plus promethazine to substantial benefit with lorazepam. 8 A single person, with a history of bronchial asthma, in the lorazepam group who complained of moderate worsening of respiratory difficulty. 9 From Analysis 1.6 of Huf 2009 2014 Il Pensiero Scientifico Editore Question: Should haloperidol plus promethazine vs midazolam be used in adults with aggression or agitation?1
Bibliography: Huf G, Alexander J, AllenMH, Raveendran NS.Haloperidol plus promethazine for psychosis-induced aggression. Cochrane Database of Systematic Reviews 2009, Issue 3. Mantovani C,
Labate CM, Sponholz A Jr, de Azevedo Marques JM, Guapo VG, de Simone Brito dos Santos ME, Pazin-Filho A, Del-Ben CM. Are low doses of antipsychotics effective in the management of
psychomotor agitation? A randomized, rated-blind trial of 4 intramuscular interventions. Journal of Clinical Psychopharmacology 2013; 33: 306-312.
Quality assessment
No of patients
Importance
Haloperidol plus
Relative
Imprecision
Midazolam
Absolute
Efficacy: NOT tranquil or asleep by 30 minutes
randomised no serious no serious 214 more per 1000 risk of bias inconsistency4 (1.75 to 4.8) (from 84 more to 428 Efficacy: NOT asleep
randomised no serious no serious 330 more per 1000 risk of bias inconsistency4 (from 184 more to Serious adverse effects
randomised no serious no serious risk of bias inconsistency4 (from 6 fewer to 99 MODERATE 1 Haloperidol IM: dose up to 10 mg + promethazine IM: dose up to 50 mg. Midazolam IM: dose up to 15 mg. 2 From Analysis 1.1 of Huf 2009 3 There is one additional study carried out by Mantovani and colleagues (2013) who compared haloperidol 2,5mg plus promethazine 25 versus haloperidol 2,5mg plus midazolam 7.5mg for the management of psychomotor agitation. Although this randomized trial enrolled a limited number of patients, it found that levels of tranquilization with the combination haloperidol 2,5mg plus promethazine 25 mg was lower than the treatment effect obtained with the combination haloperidol 2,5mg plus midazolam 7.5mg. The study concluded that low doses of haloperidol combined with midazolam can be effective in reducing psychomotor agitation without increasing the risk of extrapyramidal effects. 4 Only one study in this analysis 5 From Analysis 1.3 of Huf 2009 6 Time until asleep: haloperidol plus promethazine: 37.4 (42.9) minutes; lorazepam: 80.6 (64.3) minutes. 7 From Analysis 1.5 of Huf 2009 8 CI ranges from substantial benefit with haloperidol plus promethazine to substantial benefit with midazolam. 9 Two serious adverse effects occurred within the first 30 minutes. One aggressive person who also suffered from epilepsy was given haloperidol (5 mg) and promethazine (50 mg) and had a seizure 15 2014 Il Pensiero Scientifico Editore minutes after the drugs were administered.With benzodiazepines the person settled and recovered fully. One person with alcohol, and perhaps cocaine-induced aggression, was given midazolam(15mg). Respiratory rate immediately fell and the person became cyanosed, but recovered fully after flumazenil (0.25 mg IM) was given and did not suffer further aggressive episodes during the stay. 2014 Il Pensiero Scientifico Editore Question: Should haloperidol plus promethazine vs haloperidol be used in adults with aggression or agitation?1
Bibliography: Huf G, Alexander J, AllenMH, Raveendran NS.Haloperidol plus promethazine for psychosis-induced aggression. Cochrane Database of Systematic Reviews 2009, Issue 3.
Quality assessment
No of patients
Quality Importance
Haloperidol plus
Relative
Imprecision
Haloperidol
Absolute
Efficacy: NOT tranquil or asleep by 20 minutes
randomised no serious no serious 162 fewer per 1000 ⊕⊕⊕⊕ CRITICAL risk of bias inconsistency3 (46.2%) (0.49 to 0.87) (from 60 fewer to 235 HIGH Efficacy: NOT asleep by 20 minutes
randomised no serious no serious 102 fewer per 1000 ⊕⊕⊕⊕ CRITICAL risk of bias inconsistency3 (92.9%) (0.82 to 0.96) (from 37 fewer to 167 HIGH Serious adverse effects
randomised no serious no serious 69 fewer per 1000 ⊕⊕⊕⊕ CRITICAL risk of bias inconsistency3 (0.01 to 0.66) (from 26 fewer to 75 1 Haloperidol IM: dose up to 10 mg + IM promethazine: dose up to 50 mg. Haloperidol IM alone: dose up to 10 mg. 2 From Analysis 2.1 of Huf 2009 3 Only one study in this analysis 4 From Analysis 2.2 of Huf 2009 5 From Analysis 2.3 of Huf 2009 6 Haloperidol on its own caused a greater incidence of acute dystonia with 10 people in this group experiencing this distressing side effect compared with none in the haloperidol plus promethazine group (1 RCT, n=298, RR 0.05 CI 0.00 to 0.76, NNH 16 CI 15 to 62). The other adverse effect recorded was seizure and here one person in each group suffered a seizure after receiving treatment. 2014 Il Pensiero Scientifico Editore Question: Should haloperidol plus promethazine vs olanzapine be used in adults with aggression or agitation?1
Bibliography: Huf G, Alexander J, AllenMH, Raveendran NS.Haloperidol plus promethazine for psychosis-induced aggression. Cochrane Database of Systematic Reviews 2009, Issue 3. Mantovani C,
Labate CM, Sponholz A Jr, de Azevedo Marques JM, Guapo VG, de Simone Brito dos Santos ME, Pazin-Filho A, Del-Ben CM. Are low doses of antipsychotics effective in the management of
psychomotor agitation? A randomized, rated-blind trial of 4 intramuscular interventions. Journal of Clinical Psychopharmacology 2013; 33: 306-312.
Quality assessment
No of patients
Importance
Haloperidol plus
Relative
Imprecision
Olanzapine
Absolute
Efficacy: NOT tranquil or asleep by 15 minutes
randomised no serious no serious 33 fewer per 1000 risk of bias inconsistency4 (from 79 fewer to 52 MODERATE Efficacy: NOT asleep by 15 minutes
randomised no serious no serious 85/150 RR 0.75 (0.6 142 fewer per 1000 risk of bias inconsistency4 (from 28 fewer to 227 Efficacy: NOT asleep by 30 minutes
randomised no serious no serious 128 fewer per 1000 risk of bias inconsistency4 (from 26 fewer to 198 Serious adverse effects
randomised no serious no serious 13 fewer per 1000 risk of bias inconsistency4 (from 19 fewer to 43 MODERATE 1 Haloperidol IM: dose up to 10mg + promethazine IM: dose up to 50 mg. Olanzapine IM: dose up to 10 mg. 2 From Analysis 3.1 of Huf 2009 3 One additional study was carried out by Mantovani and colleagues (2013) who compared olanzapine 10 mg versus haloperidol 2,5mg plus promethazine 25 mg for the management of psychomotor agitation. Although this randomized trial enrolled a limited number of patients, it found that levels of tranquilization with the combination haloperidol 2,5mg plus promethazine 25 mg was lower than the treatment effect obtained with olanzapine. 4 Only one study in this analysis. 2014 Il Pensiero Scientifico Editore 5 CI ranges from substantial benefit with haloperidol plus promethazine to no difference at all. 6 After one hour: haloperidol plus promethazine: 1/150 NOT asleep; olanzapine: 9/150 Not asleep = RR 0.11 (0.01 to 0.87) in favour of the combination. 7 From Analysis 3.3 of Huf 2009 8 Similar differences after 1, 2 and 4 hours in favour of haloperidol plus promethazine. 9 From Analysis 3.6 of Huf 2009 10 CI ranges from substantial benefit with aloperidol plus promethazine to substantial benefit with olanzapine. 11 Only one person suffered a serious adverse effect in the haloperidol plus promethazine group (dehydration) and three people in the olanzapine group (two akathisia, one nausea). 2014 Il Pensiero Scientifico Editore Question: Should olanzapine vs haloperidol be used in adults with aggression or agitation?
Bibliography: Belgamwar RB, Fenton M. Olanzapine IM or velotab for acutely disturbed/agitated people with suspected serious mental illnesses. Cochrane Database of Systematic Reviews 2005, Issue
2.
Quality assessment
No of patients
Importance
Relative
Risk of bias
Inconsistency Indirectness Imprecision
Olanzapine Haloperidol
Absolute
Global effect: Did not respond - by 2 hours
randomised no serious RR 1 (0.73 to 0 fewer per 1000 (from 80 fewer to 112 more) Adverse event: EPS - akathisia - by 5 days
randomised no serious RR 0.51 (0.32 173 fewer per 1000 (from 71 fewer to 240 fewer) MODERATE Adverse event: EPS - requiring anticholinergic medication
randomised no serious RR 0.20 (0.09 140 fewer per 1000 (from 98 fewer to 159 fewer) MODERATE 1 From Analysis 2.1 of Belgamwar 2005. Haloperidol IM 7.5mg; olanzapine IM 10mg. 2 Mild agitation patients only. 3 From Analysis 2.5 of Belgamwar 2005 4 Only one study in this analysis. 5 From Analysis 2.6 of Belgamwar 2005 2014 Il Pensiero Scientifico Editore Question: Should olanzapine vs benzodiazepines be used in adults with aggression or agitation?
Bibliography: Belgamwar RB, Fenton M. Olanzapine IM or velotab for acutely disturbed/agitated people with suspected serious mental illnesses. Cochrane Database of Systematic Reviews 2005, Issue
2.
Quality assessment
No of patients
Quality Importance
Relative
Risk of bias
Inconsistency Indirectness Imprecision
Olanzapine Benzodiazepines
Absolute
Global effect: Did not respond - by 2 hours
randomised no serious RR 0.92 (0.66 25 fewer per 1000 (from ⊕⊕ΟΟ CRITICAL 106 fewer to 93 more) Adverse event: Any treatment emergent adverse event - by 24 hours
randomised no serious RR 0.62 (0.43 216 fewer per 1000 (from ⊕⊕ΟΟ CRITICAL 63 fewer to 324 fewer) 1 From Analysis 3.2 of Belgamwar 2005. Lorazepam 1.2 mg IM. Olanzapine 10 mg IM. 2 Visual inspection of forest plot suggests significant heterogeneity. I-squared = 82%. 3 Mild patient population only. 4 From Analysis 3.9 of Belgamwar 2005 5 Only one study in this analysis. 6 Less than 200 patients in this analysis. 2014 Il Pensiero Scientifico Editore Question: Should haloperidol vs aripiprazole be used for adults with aggression or agitation?
Bibliography: Powney MJ, Adams CE, Jones H.Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation). Cochrane Database of Systematic Reviews 2012, Issue 11.
Quality assessment
No of patients
Quality Importance
Relative
Risk of bias
Indirectness Imprecision
Haloperidol Aripiprazole
Absolute
needing additional injection
no serious risk no serious RR 0.78 (0.62 90 fewer per 1000 (from 4 ⊕⊕ΟΟ CRITICAL fewer to 156 fewer) one or more drug related adverse effects
no serious risk no serious RR 1.18 (0.95 69 more per 1000 (from 19 ⊕⊕ΟΟ CRITICAL fewer to 176 more) 1 Analysis 2.1 of Powney 2012. 2 Mild patient populations only. Haloperidol was administered orally, intramuscularly or intravenously. 3 Confidence interval ranges from substantial benefit with haloperidol to almost no difference. 4 Analysis 2.7 of Powney 2012 5 Confidence interval ranges from substantial benefit with aripiprazole to no difference. 2014 Il Pensiero Scientifico Editore Belgamwar RB, Fenton M. Olanzapine IM or velotab for acutely disturbed/agitated people with suspected serious mental il nesses. Cochrane Database of Systematic Reviews 2005, Issue 2. Berk M, Rathbone J, Mandriota-Carpenter SL. Clotiapine for acute psychotic il nesses. Cochrane Database of Systematic Reviews 2004, Issue 4. Gibson RC, Fenton M, da Silva Freire Coutinho E, Campbel C. Zuclopenthixol acetate for acute schizophrenia and similar serious mental il nesses. Cochrane Database of Systematic Reviews 2004, Issue 3. Gil ies D, Beck A,McCloud A, Rathbone J. Benzodiazepines for psychosis-induced aggression or agitation. Cochrane Database of Systematic Reviews 2005, Issue 4. Hohl et al. Safety and Clinical Effectiveness of Midazolam versus Propofol for Procedural Sedation in the Emergency Department: A Systematic Review Academic Emergency Medicine 2008; 15: 1–8. Huf G, Alexander J, Al enMH, Raveendran NS. Haloperidol plus promethazine for psychosis-induced aggression. Cochrane Database of Systematic Reviews 2009, Issue 3. Isbister GK, Calver LA, Page CB, Stokes B, Bryant JL, Downes MA. Randomized control ed trial of intramuscular droperidol versus midazolam for violence and acute behavioral disturbance: the DORM study. Annals of Emergency Medicine 2010; 56: 392-401. Leucht C, Kitzmantel M, Kane J, Leucht S, Chua WLLC. Haloperidol versus chlorpromazine for schizophrenia. Cochrane Database of Systematic Reviews 2008, Issue 1. Nobay F, Simon BC, Levitt MA, Dresden GM. A prospective, double-blind, randomized trial of midazolam versus haloperidol versus lorazepam in the chemical restraint of violent and severely agitated patients. Academy of Emergency Medicine 2004; 11: 744-9. Powney MJ, Adams CE, Jones H. Haloperidol for psychosis-induced aggression or agitation (rapid tranquil isation). Cochrane Database of Systematic Reviews 2012, Issue 11. 2014 Il Pensiero Scientifico Editore

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