Cochrane · systematic review · CD009377

Haloperidol for psychosis‐induced aggression or agitation (rapid tranquillisation)

Ostinelli, EG, Brooke‐Powney, MJ, Li, X, et al. · Cochrane Database of Systematic Reviews · 2017 · Cochrane Library

Schizophrenia2 versionsAMSTAR 2: not assessed

SoF tableOnly the outcomes this review put in its Summary of Findings table are listed (the Cochrane Handbook caps them at about seven per comparison). Its other analyses are not shown here.

Questions

153

current version

GRADE rated

No studies

Included studies

No studies 62 · 40.5%Ungraded 1 · 0.7%Very low 64 · 41.8%Low 18 · 11.8%Moderate 8 · 5.2%High 0 · 0%

Ungraded means an effect was reported without a GRADE rating; it is not a gap. No studies means the review found nothing to answer the question. The six categories are a display order, not a score.

Questions and results

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HALOPERIDOL compared to PLACEBO/NIL for psychosis‐induced aggression or agitation

Population: patients with psychosis‐induced aggression or agitation

6 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep not asleep at 2 hours HALOPERIDOL vs PLACEBO/NIL	RR 0.88 [0.82, 0.95]	2 studies · 220 participants	Very low Downgraded: risk of bias, indirectness, publication bias
Repeated need for tranquillisation needing additional injection within 24 hours HALOPERIDOL vs PLACEBO/NIL	RR 0.51 [0.42, 0.62]	4 studies · 660 participants	Low Downgraded: risk of bias, publication bias
Specific behaviour ‐ threat or injury to self or others average change score (ABS, high = worse) at 2 hours HALOPERIDOL vs PLACEBO/NIL	no estimate extracted	3 studies · 474 participants	Very low Downgraded: risk of bias, indirectness, publication bias
Global outcome ‐ overall improvement (not any improvement) HALOPERIDOL vs PLACEBO/NIL	RR 0.28 [0.08, 1.07]	1 study · 40 participants	Low Downgraded: risk of bias, imprecision
Adverse effects: Specific ‐ dystonia within 24 hours HALOPERIDOL vs PLACEBO/NIL	RR 7.49 [0.93, 60.21]	2 studies · 207 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Economic outcome ‐ not reported HALOPERIDOL vs PLACEBO/NIL	no estimate extracted	NR	No studies

HALOPERIDOL compared to OTHER ANTIPSYCHOTIC: a. ARIPIPRAZOLE for psychosis‐induced aggression or agitation

Population: patients with psychosis‐induced aggression or agitation

6 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: a. ARIPIPRAZOLE	no estimate extracted	NR	No studies
Repeated need for rapid tranquillisation ‐ needing additional injection HALOPERIDOL vs OTHER ANTIPSYCHOTIC: a. ARIPIPRAZOLE	RR 0.78 [0.62, 0.99]	2 studies · 473 participants	Low Downgraded: risk of bias, publication bias
Specific behaviours ‐ agitation: CABS average change score at 2 hours HALOPERIDOL vs OTHER ANTIPSYCHOTIC: a. ARIPIPRAZOLE	no estimate extracted	2 studies · 470 participants	Very low Downgraded: risk of bias, indirectness
Global outcomes: need for benzodiazepine 2 HALOPERIDOL vs OTHER ANTIPSYCHOTIC: a. ARIPIPRAZOLE	RR 1.26 [0.74, 2.16]	2 studies · 477 participants	Very low Downgraded: risk of bias, indirectness, publication bias
Adverse effects: any serious, specific ‐ dystonia during 24 hours HALOPERIDOL vs OTHER ANTIPSYCHOTIC: a. ARIPIPRAZOLE	RR 6.63 [1.52, 28.86]	2 studies · 477 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Economic outcome ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: a. ARIPIPRAZOLE	no estimate extracted	NR	No studies

HALOPERIDOL compared to OTHER ANTIPSYCHOTIC: b. CHLORPROMAZINE for psychosis‐induced aggression or agitation

Population: patients with psychosis‐induced aggression or agitation

7 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep Not tranquil or asleep HALOPERIDOL vs OTHER ANTIPSYCHOTIC: b. CHLORPROMAZINE	RR 1.93 [1.04, 3.6]	1 study · 39 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Repeated need for rapid tranquillisation ‐ more that 1 injection HALOPERIDOL vs OTHER ANTIPSYCHOTIC: b. CHLORPROMAZINE	RR 1.07 [0.89, 1.28]	1 study · 30 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Specific behaviour ‐ threat or injury of harm to self or others ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: b. CHLORPROMAZINE	no estimate extracted	NR	No studies
Global outcome ‐ not any improvement HALOPERIDOL vs OTHER ANTIPSYCHOTIC: b. CHLORPROMAZINE	RR 0.15 [0.05, 0.49]	2 studies · 89 participants	Very low Downgraded: risk of bias, imprecision
Adverse effects: specific ‐ cardiovascular ‐ hypotension HALOPERIDOL vs OTHER ANTIPSYCHOTIC: b. CHLORPROMAZINE	RR 0.51 [0.01, 2.6]	1 study · 30 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Adverse effects: specific ‐ central nervous system ‐ seizures HALOPERIDOL vs OTHER ANTIPSYCHOTIC: b. CHLORPROMAZINE	RR 0.33 [0.01, 7.58]	1 study · 30 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Economic outcome ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: b. CHLORPROMAZINE	no estimate extracted	NR	No studies

HALOPERIDOL compared to OTHER ANTIPSYCHOTIC: c. DROPERIDOL for psychosis‐induced aggression or agitation

Population: psychosis‐induced aggression or agitation

6 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not asleep up to 2 hours HALOPERIDOL vs OTHER ANTIPSYCHOTIC: c. DROPERIDOL	RR 1.07 [0.44, 2.6]	1 study · 228 participants	Moderate
Repeated need for rapid tranquillisation ‐ more than 1 injection HALOPERIDOL vs OTHER ANTIPSYCHOTIC: c. DROPERIDOL	RR 2.38 [1.27, 4.47]	2 studies · 255 participants	Moderate Downgraded: risk of bias, imprecision, publication bias
Specific behaviour ‐ threat or injury to self or others ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: c. DROPERIDOL	no estimate extracted	NR	No studies
Global outcome ‐ need for benzodiazepine HALOPERIDOL vs OTHER ANTIPSYCHOTIC: c. DROPERIDOL	RR 0.31 [0.07, 1.44]	1 study · 228 participants	Moderate
Adverse effects: specific ‐ dystonia HALOPERIDOL vs OTHER ANTIPSYCHOTIC: c. DROPERIDOL	RR 0.86 [0.11, 6.56]	2 studies · 255 participants	Moderate Downgraded: risk of bias, imprecision, publication bias
Economic outcome ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: c. DROPERIDOL	no estimate extracted	NR	No studies

HALOPERIDOL compared to OTHER ANTIPSYCHOTIC: d. LOXAPINE for psychosis‐induced aggression or agitation

Population: patients to psychosis‐induced aggression or agitation

7 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not asleep by 12 hours HALOPERIDOL vs OTHER ANTIPSYCHOTIC: d. LOXAPINE	RR 4.31 [0.54, 34.48]	1 study · 54 participants	Very low Downgraded: risk of bias, imprecision, inconsistency, indirectness
Global outcome: specific Not sedated at 60 minutes * HALOPERIDOL vs OTHER ANTIPSYCHOTIC: d. LOXAPINE	RR 3.5 [0.86, 14.18]	1 study · 30 participants	Very low Downgraded: risk of bias, imprecision, inconsistency, indirectness, publication bias
Specific behaviour ‐ aggression ‐ no overall improvement HALOPERIDOL vs OTHER ANTIPSYCHOTIC: d. LOXAPINE	RR 1.1 [0.69, 1.76]	1 study · 30 participants	Very low Downgraded: risk of bias, imprecision, inconsistency, indirectness, publication bias
Global outcome: no change at 48 hours CGI HALOPERIDOL vs OTHER ANTIPSYCHOTIC: d. LOXAPINE	RR 0.93 [0.14, 6.15]	1 study · 56 participants	Low Downgraded: risk of bias, imprecision, inconsistency
Adverse effects: Specific ‐ dystonia between 0‐3 days (IM phase) HALOPERIDOL vs OTHER ANTIPSYCHOTIC: d. LOXAPINE	RR 0.94 [0.06, 13.93]	1 study · 35 participants	Very low Downgraded: risk of bias, imprecision, inconsistency
Adverse effects: Specific ‐ rigidity between 0‐3 days (IM phase) HALOPERIDOL vs OTHER ANTIPSYCHOTIC: d. LOXAPINE	RR 0.88 [0.65, 1.19]	1 study · 35 participants	Very low Downgraded: risk of bias, imprecision, inconsistency, publication bias
Economic outcome ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: d. LOXAPINE	no estimate extracted	NR	No studies

HALOPERIDOL compared to OTHER ANTIPSYCHOTIC: e. OLANZAPINE for psychosis induced aggression or agitation

Population: psychosis induced aggression or agitation

6 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquilisation or asleep HALOPERIDOL vs OTHER ANTIPSYCHOTIC: e. OLANZAPINE	RR 1.16 [1.02, 1.32]	1 study · 257 participants	Very low Downgraded: risk of bias, imprecision, indirectness, publication bias
Repeated need for tranquillisation HALOPERIDOL vs OTHER ANTIPSYCHOTIC: e. OLANZAPINE	RR 1.06 [0.75, 1.51]	3 studies · 392 participants	Very low Downgraded: risk of bias, imprecision, indirectness, publication bias
Specific behaviour ‐ threat or injury to self or others HALOPERIDOL vs OTHER ANTIPSYCHOTIC: e. OLANZAPINE	RR 0.96 [0.58, 1.58]	1 study · 45 participants	Very low Downgraded: risk of bias, imprecision, indirectness, publication bias
Global outcome ‐ need for benzodiazepine during 24 hours HALOPERIDOL vs OTHER ANTIPSYCHOTIC: e. OLANZAPINE	RR 1.05 [0.63, 1.74]	2 studies · 343 participants	Very low Downgraded: risk of bias, imprecision, indirectness, publication bias
Adverse effects: Specific ‐ dystonia during 24 hours HALOPERIDOL vs OTHER ANTIPSYCHOTIC: e. OLANZAPINE	RR 12.92 [1.67, 99.78]	2 studies · 343 participants	Very low Downgraded: risk of bias, imprecision, indirectness, publication bias
Economic outcome ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: e. OLANZAPINE	no estimate extracted	NR	No studies

HALOPERIDOL compared to OTHER ANTIPSYCHOTIC: f. PERPHENAZINE for psychosis‐induced aggression or agitation

Population: patients with psychosis‐induced aggression or agitation

7 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: f. PERPHENAZINE	no estimate extracted	NR	No studies
Repeated need for rapid tranquillisation ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: f. PERPHENAZINE	no estimate extracted	NR	No studies
Specific behaviour ‐ injury or threat of self to others ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: f. PERPHENAZINE	no estimate extracted	NR	No studies
Global outcome: general ‐ no improvement HALOPERIDOL vs OTHER ANTIPSYCHOTIC: f. PERPHENAZINE	RR 0.46 [0.04, 4.68]	1 study · 44 participants	Very low Downgraded: risk of bias, publication bias
Adverse effect: Specific ‐ hypotensive episode HALOPERIDOL vs OTHER ANTIPSYCHOTIC: f. PERPHENAZINE	RR 0.31 [0.01, 7.12]	1 study · 44 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Adverse effect ‐ discontinued due to EPS HALOPERIDOL vs OTHER ANTIPSYCHOTIC: f. PERPHENAZINE	RR 1.83 [0.18, 18.7]	1 study · 44 participants	Very low Downgraded: risk of bias, indirectness, publication bias
Economic outcome ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: f. PERPHENAZINE	no estimate extracted	NR	No studies

HALOPERIDOL compared to OTHER ANTIPSYCHOTICS: g. QUETIAPINE for psychosis‐induced aggression or agitation

Population: psychosis‐induced aggression or agitation

6 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTICS: g. QUETIAPINE	no estimate extracted	NR	No studies
Repeated need for tranquillisation ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTICS: g. QUETIAPINE	no estimate extracted	NR	No studies
Specific behaviour ‐ agitation HALOPERIDOL vs OTHER ANTIPSYCHOTICS: g. QUETIAPINE	no estimate extracted	1 study · 80 participants	Low Downgraded: imprecision
Global outcome ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTICS: g. QUETIAPINE	no estimate extracted	NR	No studies
Adverse effects HALOPERIDOL vs OTHER ANTIPSYCHOTICS: g. QUETIAPINE	RR 1.81 [1.19, 2.77]	1 study · 80 participants	Low Downgraded: imprecision
Economic outcome ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTICS: g. QUETIAPINE	no estimate extracted	NR	No studies

HALOPERIDOL compared to OTHER ANTIPSYCHOTIC: h. RISPERIDONE for psychosis‐induced aggression or agitation

Population: patients with psychosis‐induced aggression or agitation

7 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not asleep HALOPERIDOL vs OTHER ANTIPSYCHOTIC: h. RISPERIDONE	RR 0.84 [0.74, 0.95]	1 study · 162 participants	Moderate Downgraded: risk of bias
Repeated need for rapid tranquillisation ‐ needing additional benzodiazepine HALOPERIDOL vs OTHER ANTIPSYCHOTIC: h. RISPERIDONE	RR 0.98 [0.65, 1.47]	2 studies · 286 participants	Low Downgraded: risk of bias, imprecision
Specific behaviours ‐ agitation >50% reduction in PANSS‐EC score HALOPERIDOL vs OTHER ANTIPSYCHOTIC: h. RISPERIDONE	RR 1.15 [0.6, 2.22]	1 study · 124 participants	Low Downgraded: risk of bias, publication bias
Global outcome ‐ rated as severe ‐ CGI‐S HALOPERIDOL vs OTHER ANTIPSYCHOTIC: h. RISPERIDONE	RR 0.89 [0.51, 1.58]	1 study · 162 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Adverse effects: Specific ‐ EPS during 24 hours HALOPERIDOL vs OTHER ANTIPSYCHOTIC: h. RISPERIDONE	RR 1.6 [0.55, 4.62]	1 study · 124 participants	Low Downgraded: risk of bias, publication bias
Adverse effects: Specific ‐ acute dystonia during 24 hours HALOPERIDOL vs OTHER ANTIPSYCHOTIC: h. RISPERIDONE	RR 5 [0.24, 102.07]	2 studies · 286 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Economic outcome ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: h. RISPERIDONE	no estimate extracted	NR	No studies

HALOPERIDOL compared to OTHER ANTIPSYCHOTIC: i. THIOTHIXENE for psychosis‐induced aggression or agitation

Population: patients with psychosis‐induced aggression or agitation

7 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: i. THIOTHIXENE	no estimate extracted	NR	No studies
Repeated need for rapid tranquillisation HALOPERIDOL vs OTHER ANTIPSYCHOTIC: i. THIOTHIXENE	RR 1.07 [0.89, 1.28]	1 study · 30 participants	Very low Downgraded: risk of bias, publication bias
Specific behaviour ‐ threat or injury to self or others ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: i. THIOTHIXENE	no estimate extracted	NR	No studies
Global outcome No improvement at 1 hour HALOPERIDOL vs OTHER ANTIPSYCHOTIC: i. THIOTHIXENE	RR 0.5 [0.14, 1.84]	1 study · 44 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Adverse effects: specific ‐ hypotensive episode HALOPERIDOL vs OTHER ANTIPSYCHOTIC: i. THIOTHIXENE	no estimate extracted	1 study · 30 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Adverse effects: specific ‐ tachycardia HALOPERIDOL vs OTHER ANTIPSYCHOTIC: i. THIOTHIXENE	RR 0.28 [0.01, 6.52]	1 study · 44 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Economic outcome ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: i. THIOTHIXENE	no estimate extracted	NR	No studies

HALOPERIDOL compared to OTHER ANTIPSYCHOTIC: j. ZIPRASIDONE for psychosis‐induced aggression or agitation

Population: psychosis‐induced aggression or agitation

7 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquilisation or asleep ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: j. ZIPRASIDONE	no estimate extracted	NR	No studies
Repeated need for tranquilisation HALOPERIDOL vs OTHER ANTIPSYCHOTIC: j. ZIPRASIDONE	RR 1.64 [1.07, 2.53]	1 study · 60 participants	Very low Downgraded: risk of bias
Specific behaviour ‐ agitation HALOPERIDOL vs OTHER ANTIPSYCHOTIC: j. ZIPRASIDONE	no estimate extracted	1 study · 231 participants	Low Downgraded: risk of bias, imprecision, indirectness, publication bias
Global outcome HALOPERIDOL vs OTHER ANTIPSYCHOTIC: j. ZIPRASIDONE	no estimate extracted	1 study · 132 participants	Very low Downgraded: risk of bias, imprecision, indirectness, publication bias
Adverse effects: Specific ‐ dystonia during 72 hours HALOPERIDOL vs OTHER ANTIPSYCHOTIC: j. ZIPRASIDONE	RR 10.26 [1.67, 63.17]	2 studies · 508 participants	Very low Downgraded: risk of bias, imprecision, indirectness, publication bias
Adverse effects: Specific ‐ clinically significant abnormal ECG during 72 hours HALOPERIDOL vs OTHER ANTIPSYCHOTIC: j. ZIPRASIDONE	RR 1.01 [0.6, 1.71]	1 study · 376 participants	Very low Downgraded: risk of bias, imprecision, indirectness, publication bias
Economic outcome ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: j. ZIPRASIDONE	no estimate extracted	NR	No studies

HALOPERIDOL compared to OTHER ANTIPSYCHOTIC: k. ZUCLOPENTHIXOL ACETATE for psychosis‐induced aggression or agitation

Population: patients with psychosis‐induced aggression or agitation

6 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: k. ZUCLOPENTHIXOL ACETATE	no estimate extracted	NR	No studies
Repeated need for rapid tranquillisation ‐ more than 3 injections HALOPERIDOL vs OTHER ANTIPSYCHOTIC: k. ZUCLOPENTHIXOL ACETATE	RR 2.54 [1.19, 5.46]	1 study · 70 participants	Very low Downgraded: risk of bias, imprecision, indirectness
Specific behaviour ‐ threat or injury to self or others ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: k. ZUCLOPENTHIXOL ACETATE	no estimate extracted	NR	No studies
Global outcome ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: k. ZUCLOPENTHIXOL ACETATE	no estimate extracted	NR	No studies
Adverse effects: specific ‐ tremor by 7 days HALOPERIDOL vs OTHER ANTIPSYCHOTIC: k. ZUCLOPENTHIXOL ACETATE	RR 4.16 [0.93, 18.62]	1 study · 70 participants	Very low Downgraded: risk of bias, imprecision, indirectness
Economic outcome ‐ not reported HALOPERIDOL vs OTHER ANTIPSYCHOTIC: k. ZUCLOPENTHIXOL ACETATE	no estimate extracted	NR	No studies

HALOPERIDOL compared to BENZODIAZEPINE: a. FLUNITRAZEPAM for psychosis‐induced aggression or agitation

Population: patients with psychosis‐induced aggression or agitation

6 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not reported HALOPERIDOL vs BENZODIAZEPINE: a. FLUNITRAZEPAM	no estimate extracted	NR	No studies
Repeated need for tranquillisation within 24 hours ‐ not reported HALOPERIDOL vs BENZODIAZEPINE: a. FLUNITRAZEPAM	no estimate extracted	NR	No studies
Specific behaviours ‐ aggression 50% reduction in OAS score at 90 minutes HALOPERIDOL vs BENZODIAZEPINE: a. FLUNITRAZEPAM	RR 1.15 [0.86, 1.55]	1 study · 28 participants	Very low Downgraded: risk of bias, indirectness, publication bias
Global outcome ‐ need for restraint or seclusion HALOPERIDOL vs BENZODIAZEPINE: a. FLUNITRAZEPAM	no estimate extracted	1 study · 28 participants	Very low Downgraded: risk of bias, imprecision, indirectness, publication bias
Adverse effects: specific ‐ EPS HALOPERIDOL vs BENZODIAZEPINE: a. FLUNITRAZEPAM	no estimate extracted	1 study · 28 participants	Very low Downgraded: risk of bias, imprecision, indirectness, publication bias
Economic outcome ‐ not reported HALOPERIDOL vs BENZODIAZEPINE: a. FLUNITRAZEPAM	no estimate extracted	NR	No studies

HALOPERIDOL compared to BENZODIAZEPINE: b. LORAZEPAM for psychosis‐induced aggression or agitation

Population: patients with psychosis‐induced aggression or agitation

7 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep not asleep at 60 minutes HALOPERIDOL vs BENZODIAZEPINE: b. LORAZEPAM	RR 1.05 [0.76, 1.44]	1 study · 60 participants	Very low Downgraded: risk of bias, imprecision, indirectness, publication bias
Repeated need for rapid tranquillisation more than 1 injection HALOPERIDOL vs BENZODIAZEPINE: b. LORAZEPAM	RR 1.14 [0.91, 1.43]	1 study · 66 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Specific behaviour ‐ threat or injury to self or others within 24 hours ‐ not reported HALOPERIDOL vs BENZODIAZEPINE: b. LORAZEPAM	no estimate extracted	NR	No studies
Global outcome: no overall improvement ‐ at 60 minutes HALOPERIDOL vs BENZODIAZEPINE: b. LORAZEPAM	RR 1.64 [0.54, 5.03]	1 study · 44 participants	Very low Downgraded: risk of bias, imprecision
Adverse effects: specific ‐ dystonia (only reported if occurred in ≥9% during 24 hours) HALOPERIDOL vs BENZODIAZEPINE: b. LORAZEPAM	RR 3.54 [0.42, 30.03]	1 study · 66 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Adverse effects: specific ‐ hypertonia/rigidity (only reported if occurred in ≥9%) during 24 hours HALOPERIDOL vs BENZODIAZEPINE: b. LORAZEPAM	RR 6.22 [0.33, 115.91]	1 study · 66 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Economic outcome ‐ not reported HALOPERIDOL vs BENZODIAZEPINE: b. LORAZEPAM	no estimate extracted	NR	No studies

HALOPERIDOL compared to BENZODIAZEPINE: c. MIDAZOLAM for psychosis‐induced aggression or agitation

Population: patients with psychosis‐induced aggression or agitation

6 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not reported HALOPERIDOL vs BENZODIAZEPINE: c. MIDAZOLAM	no estimate extracted	NR	No studies
Repeated need for rapid tranquillisation ‐ not reported HALOPERIDOL vs BENZODIAZEPINE: c. MIDAZOLAM	no estimate extracted	NR	No studies
Specific behaviour ‐ threat or injury to self or others ‐ not reported HALOPERIDOL vs BENZODIAZEPINE: c. MIDAZOLAM	no estimate extracted	NR	No studies
Global outcome Need for rescue drug HALOPERIDOL vs BENZODIAZEPINE: c. MIDAZOLAM	RR 1.14 [0.46, 2.87]	1 study · 84 participants	Low Downgraded: imprecision, indirectness
Adverse effects ‐ general ‐ one or more drug‐related adverse effect HALOPERIDOL vs BENZODIAZEPINE: c. MIDAZOLAM	RR 5 [0.25, 101.11]	1 study · 84 participants	Low Downgraded: imprecision, indirectness
Economic outcome ‐ not reported HALOPERIDOL vs BENZODIAZEPINE: c. MIDAZOLAM	no estimate extracted	NR	No studies

HALOPERIDOL compared to COMBINATIONS: a. HALOPERIDOL + LEVOMEPROMAZINE for psychosis‐induced aggression or agitation

Population: patients with psychosis‐induced aggression or agitation

6 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not reported HALOPERIDOL vs COMBINATIONS: a. HALOPERIDOL + LEVOMEPROMAZINE	no estimate extracted	NR	No studies
Repeated need for tranquillisation ‐ not reported HALOPERIDOL vs COMBINATIONS: a. HALOPERIDOL + LEVOMEPROMAZINE	no estimate extracted	NR	No studies
Specific behaviours ‐ threat or injury to self or others ‐ not reported HALOPERIDOL vs COMBINATIONS: a. HALOPERIDOL + LEVOMEPROMAZINE	no estimate extracted	NR	No studies
Global outcome: general ‐ no overall improvement HALOPERIDOL vs COMBINATIONS: a. HALOPERIDOL + LEVOMEPROMAZINE	RR 8.18 [0.5, 133.66]	1 study · 19 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Adverse effect: any serious, specific ‐ not reported HALOPERIDOL vs COMBINATIONS: a. HALOPERIDOL + LEVOMEPROMAZINE	no estimate extracted	NR	No studies
Economic outcome ‐ not measured HALOPERIDOL vs COMBINATIONS: a. HALOPERIDOL + LEVOMEPROMAZINE	no estimate extracted	NR	No studies

HALOPERIDOL compared to COMBINATIONS: b. HALOPERIDOL + LORAZEPAM for psychosis‐induced aggression or agitation

Population: patients with psychosis‐induced aggression or agitation

7 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not asleep by 3 hours HALOPERIDOL vs COMBINATIONS: b. HALOPERIDOL + LORAZEPAM	RR 1.83 [1.11, 3.02]	1 study · 67 participants	Very low Downgraded: risk of bias, imprecision, indirectness, publication bias
Repeated need for rapid tranquillisation ‐ needing additional injection during 24 hours HALOPERIDOL vs COMBINATIONS: b. HALOPERIDOL + LORAZEPAM	RR 1.05 [0.87, 1.27]	1 study · 67 participants	Very low Downgraded: risk of bias, imprecision, publication bias
Specific behaviour ‐ threat or injury to self or others ‐ not reported HALOPERIDOL vs COMBINATIONS: b. HALOPERIDOL + LORAZEPAM	no estimate extracted	NR	No studies
Global outcome: no overall improvement ‐ at 30 minutes HALOPERIDOL vs COMBINATIONS: b. HALOPERIDOL + LORAZEPAM	RR 2.67 [1.25, 5.68]	1 study · 45 participants	Very low Downgraded: risk of bias, imprecision
Adverse effects: Specific ‐ dystonia (only reported if occurred in ≥9%) during 24 hours HALOPERIDOL vs COMBINATIONS: b. HALOPERIDOL + LORAZEPAM	RR 8.25 [0.46, 147.45]	1 study · 67 participants	Very low Downgraded: risk of bias, imprecision, indirectness, publication bias
Adverse effects: Specific ‐ hypertonia/rigidity (only reported if occurred in ≥9%) during 24 hours HALOPERIDOL vs COMBINATIONS: b. HALOPERIDOL + LORAZEPAM	RR 2.74 [0.3, 25.05]	1 study · 67 participants	Very low Downgraded: risk of bias, imprecision, indirectness, publication bias
Economic outcome ‐ not reported HALOPERIDOL vs COMBINATIONS: b. HALOPERIDOL + LORAZEPAM	no estimate extracted	NR	No studies

HALOPERIDOL compared to COMBINATIONS: c. HALOPERIDOL + MIDAZOLAM for psychosis‐induced aggression or agitation

Population: psychosis‐induced aggression or agitation

6 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not reported HALOPERIDOL vs COMBINATIONS: c. HALOPERIDOL + MIDAZOLAM	no estimate extracted	NR	No studies
Repeated need for tranquillisation HALOPERIDOL vs COMBINATIONS: c. HALOPERIDOL + MIDAZOLAM	RR 0.88 [0.69, 1.13]	1 study · 60 participants	Very low Downgraded: risk of bias
Specific behaviour ‐ agitation HALOPERIDOL vs COMBINATIONS: c. HALOPERIDOL + MIDAZOLAM	no estimate extracted	1 study · 60 participants	Very low Downgraded: risk of bias
Global outcome HALOPERIDOL vs COMBINATIONS: c. HALOPERIDOL + MIDAZOLAM	RR 0.29 [0.13, 0.61]	1 study · 60 participants	Very low Downgraded: risk of bias
Adverse effects HALOPERIDOL vs COMBINATIONS: c. HALOPERIDOL + MIDAZOLAM	RR 1.67 [0.44, 6.36]	1 study · 60 participants	Very low Downgraded: risk of bias
Economic outcome ‐ not reported HALOPERIDOL vs COMBINATIONS: c. HALOPERIDOL + MIDAZOLAM	no estimate extracted	NR	No studies

HALOPERIDOL compared to COMBINATIONS: d. HALOPERIDOL + PROMETHAZINE for psychosis‐induced aggression or agitation

Population: psychosis‐induced aggression or agitation

7 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep HALOPERIDOL vs COMBINATIONS: d. HALOPERIDOL + PROMETHAZINE	RR 1.6 [1.18, 2.16]	1 study · 316 participants	Moderate Downgraded: risk of bias
Repeated need for tranquillisation HALOPERIDOL vs COMBINATIONS: d. HALOPERIDOL + PROMETHAZINE	RR 0.78 [0.43, 1.41]	2 studies · 376 participants	Very low Downgraded: risk of bias
Specific behaviours ‐ aggression HALOPERIDOL vs COMBINATIONS: d. HALOPERIDOL + PROMETHAZINE	RR 1.06 [0.68, 1.65]	1 study · 316 participants	Moderate Downgraded: risk of bias
Global outcomes HALOPERIDOL vs COMBINATIONS: d. HALOPERIDOL + PROMETHAZINE	RR 1.21 [0.84, 1.76]	1 study · 316 participants	Moderate Downgraded: risk of bias
Adverse effects: specific ‐ acute dystonia HALOPERIDOL vs COMBINATIONS: d. HALOPERIDOL + PROMETHAZINE	RR 19.48 [1.14, 331.92]	1 study · 316 participants	Low Downgraded: risk of bias
Adverse effects: specific ‐ seizure HALOPERIDOL vs COMBINATIONS: d. HALOPERIDOL + PROMETHAZINE	RR 2.05 [0.19, 22.39]	1 study · 316 participants	Low Downgraded: risk of bias
Economic outcome ‐ not reported HALOPERIDOL vs COMBINATIONS: d. HALOPERIDOL + PROMETHAZINE	no estimate extracted	NR	No studies

HALOPERIDOL compared to COMBINATIONS: e. HALOPERIDOL + RISPERIDONE for psychosis‐induced aggression or agitation

Population: psychosis‐induced aggression or agitation

6 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not reported HALOPERIDOL vs COMBINATIONS: e. HALOPERIDOL + RISPERIDONE	no estimate extracted	NR	No studies
Repeated need for tranquillisation ‐ not reported HALOPERIDOL vs COMBINATIONS: e. HALOPERIDOL + RISPERIDONE	no estimate extracted	NR	No studies
Specific behaviour ‐ agitation HALOPERIDOL vs COMBINATIONS: e. HALOPERIDOL + RISPERIDONE	no estimate extracted	1 study · 100 participants	Low Downgraded: risk of bias
Global outcome HALOPERIDOL vs COMBINATIONS: e. HALOPERIDOL + RISPERIDONE	RR 0.38 [0.11, 1.33]	1 study · 100 participants	Low Downgraded: risk of bias
Adverse effects: specific HALOPERIDOL vs COMBINATIONS: e. HALOPERIDOL + RISPERIDONE	RR 0.88 [0.48, 1.6]	1 study · 100 participants	Low Downgraded: risk of bias
Economic outcome ‐ not reported HALOPERIDOL vs COMBINATIONS: e. HALOPERIDOL + RISPERIDONE	no estimate extracted	NR	No studies

HALOPERIDOL compared to COMBINATIONS: f. OLANZAPINE + MAGNESIUM VALPROATE for psychosis‐induced aggression or agitation

Population: psychosis‐induced aggression or agitation

6 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not reported HALOPERIDOL vs COMBINATIONS: f. OLANZAPINE + MAGNESIUM VALPROATE	no estimate extracted	NR	No studies
Repeated need for tranquillisation ‐ not reported HALOPERIDOL vs COMBINATIONS: f. OLANZAPINE + MAGNESIUM VALPROATE	no estimate extracted	NR	No studies
Specific behaviour ‐ agitation HALOPERIDOL vs COMBINATIONS: f. OLANZAPINE + MAGNESIUM VALPROATE	no estimate extracted	1 study · 64 participants	Very low Downgraded: risk of bias
Global outcome HALOPERIDOL vs COMBINATIONS: f. OLANZAPINE + MAGNESIUM VALPROATE	RR 1.06 [0.38, 2.95]	1 study · 64 participants	Very low Downgraded: risk of bias
Adverse effects HALOPERIDOL vs COMBINATIONS: f. OLANZAPINE + MAGNESIUM VALPROATE	RR 3.06 [1.62, 5.79]	1 study · 64 participants	Very low Downgraded: risk of bias
Economic outcome ‐ not reported HALOPERIDOL vs COMBINATIONS: f. OLANZAPINE + MAGNESIUM VALPROATE	no estimate extracted	NR	No studies

HALOPERIDOL compared to COMBINATIONS: g. QUETIAPINE + MAGNESIUM VALPROATE for psychosis‐induced aggression or agitation

Population: patients with psychosis‐induced aggression or agitation

6 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not reported HALOPERIDOL vs COMBINATIONS: g. QUETIAPINE + MAGNESIUM VALPROATE	no estimate extracted	NR	No studies
Repeated need for tranquillisation ‐ not reported HALOPERIDOL vs COMBINATIONS: g. QUETIAPINE + MAGNESIUM VALPROATE	no estimate extracted	NR	No studies
Specific behaviours ‐ agitation at 3 days average endpoint score (PANSS‐EC) HALOPERIDOL vs COMBINATIONS: g. QUETIAPINE + MAGNESIUM VALPROATE	no estimate extracted	1 study · 60 participants	Very low Downgraded: risk of bias, indirectness
Global effect Specific behaviour ‐ agitation ‐ no effect based on PANSS‐EC (< 25% decrease) HALOPERIDOL vs COMBINATIONS: g. QUETIAPINE + MAGNESIUM VALPROATE	RR 1.17 [0.44, 3.06]	1 study · 60 participants	Very low Downgraded: risk of bias, indirectness
Adverse effects ‐ any specific, serious ‐ not reported HALOPERIDOL vs COMBINATIONS: g. QUETIAPINE + MAGNESIUM VALPROATE	no estimate extracted	NR	No studies
Economic outcome ‐ not reported HALOPERIDOL vs COMBINATIONS: g. QUETIAPINE + MAGNESIUM VALPROATE	no estimate extracted	0 studies · 0 participants	Ungraded

HALOPERIDOL compared to COMBINATIONS: h. RISPERIDONE + CLONAZEPAM for psychosis induced aggression or agitation

Population: psychosis induced aggression or agitation

6 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep HALOPERIDOL vs COMBINATIONS: h. RISPERIDONE + CLONAZEPAM	RR 0.82 [0.66, 1.03]	1 study · 205 participants	Very low Downgraded: risk of bias
Repeated need for tranquillisation ‐ not reported HALOPERIDOL vs COMBINATIONS: h. RISPERIDONE + CLONAZEPAM	no estimate extracted	NR	No studies
Specific behaviour ‐ agitation HALOPERIDOL vs COMBINATIONS: h. RISPERIDONE + CLONAZEPAM	no estimate extracted	1 study · 108 participants	Very low Downgraded: risk of bias
Global outcome HALOPERIDOL vs COMBINATIONS: h. RISPERIDONE + CLONAZEPAM	RR 0.6 [0.15, 2.38]	1 study · 100 participants	Low Downgraded: risk of bias, imprecision
Adverse effects HALOPERIDOL vs COMBINATIONS: h. RISPERIDONE + CLONAZEPAM	RR 1.63 [1.12, 2.38]	1 study · 205 participants	Very low Downgraded: risk of bias
Economic outcome ‐ not reported HALOPERIDOL vs COMBINATIONS: h. RISPERIDONE + CLONAZEPAM	no estimate extracted	NR	No studies

HALOPERIDOL compared to COMBINATIONS: i. ZIPRASIDONE + CLONAZEPAM for psychosis‐induced aggression or agitation

Population: psychosis‐induced aggression or agitation

6 questions

Outcome	Effect	Evidence	Status / GRADE
Tranquillisation or asleep ‐ not reported HALOPERIDOL vs COMBINATIONS: i. ZIPRASIDONE + CLONAZEPAM	no estimate extracted	NR	No studies
Repeated need for tranquillisation ‐ not reported HALOPERIDOL vs COMBINATIONS: i. ZIPRASIDONE + CLONAZEPAM	no estimate extracted	NR	No studies
Specific behaviour ‐ agitation HALOPERIDOL vs COMBINATIONS: i. ZIPRASIDONE + CLONAZEPAM	no estimate extracted	1 study · 71 participants	Very low Downgraded: risk of bias
Global outcome ‐ no improvement ‐ not reported HALOPERIDOL vs COMBINATIONS: i. ZIPRASIDONE + CLONAZEPAM	no estimate extracted	NR	No studies
Adverse effects ‐ not reported HALOPERIDOL vs COMBINATIONS: i. ZIPRASIDONE + CLONAZEPAM	no estimate extracted	NR	No studies
Economic outcome ‐ not reported HALOPERIDOL vs COMBINATIONS: i. ZIPRASIDONE + CLONAZEPAM	no estimate extracted	NR	No studies