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Cochrane Database of Systematic Reviews

Haloperidol plus promethazine for psychosis‐induced aggression

Information

DOI:
https://doi.org/10.1002/14651858.CD005146.pub3Copy DOI
Database:
  1. Cochrane Database of Systematic Reviews
Version published:
  1. 25 November 2016see what's new
Type:
  1. Intervention
Stage:
  1. Review
Cochrane Editorial Group:
  1. Cochrane Schizophrenia Group

Copyright:
  1. Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Authors

  • Gisele Huf

    Correspondence to: National Institute of Quality Control in Health, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil

    [email protected]

    [email protected]

  • Jacob Alexander

    Department of Psychiatry, Mental Health Centre, Christian Medical Centre, Vellore, India

  • Pinky Gandhi

    Nottingham, UK

  • Michael H Allen

    Department of Psychiatry, University of Colorado Depression Centre, Aurora, USA

Contributions of authors

Gisele Huf helped write the protocol, formulate searches, select studies, extract data, format the review, and write the report.

Jacob Alexander helped write the protocol, formulate searches, select studies, extract data, format the review, and write the report.

Michael H Allen helped edit the protocol and final report.

Pinky Ghandi completed trial selection and data extraction for the 2015 update.

Sources of support

Internal sources

  • Universidade Federal de Rio de Janeiro, Brazil.

  • Christian Medical Centre, Vellore, India.

  • University of Colorado School of Medicine, USA.

  • National Institute of Quality Control in Health, Oswald Cruz Foundation, Brazil.

External sources

  • No sources of support supplied

Declarations of interest

GH: is an author of the included studies (TREC‐Rio‐I; TREC‐Rio‐II) see Potential biases in the review process for more information. No other conflict of interest.

JA: is an author of included studies (TREC‐Vellore‐I; TREC‐Vellore‐II) see Potential biases in the review process for more information. No other conflict of interest.

PG: no conflict of interest.

MHA: Michael was involved in the development of inhaled loxapine with Alexza and continued to work on the 'Phase 4 programme' with Ferrer in Europe. He was also involved in some advisory and educational programme development with Teva around inhaled loxapine. This might be considered an alternative to haloperidol and promethazine in the developed world.

Acknowledgements

2009 version: The review authors would like to thank Edwardo da Silveira Martins (Pharmacy of Pinel hospital, Rio de Janeiro, Brazil) for his detailed provision of pharmacokinetic data on lorazepam and midazolam. We would also like to thank Clive E Adams, Tessa Grant, and Gill Rizzello of the Cochrane Schizophrenia Group for their editorial help.

Without the help of Clive E Adams for the 2015 update, we would not have been able to re‐extract all data, find the new studies, and complete the update in such a timely manner. We would also like to thank Nirmal Raveendran who helped update a previous version of this review of 2008.

Parts of this review were generated using RevMan HAL v 4.2. You can find more information about RevMan HAL here.

We would also like to thank and acknowledge Joanna Hubert, Sarah Barber, and Suravi Patra for peer reviewing this version of the review.

Version history

Published

Title

Stage

Authors

Version

2016 Nov 25

Haloperidol plus promethazine for psychosis‐induced aggression

Review

Gisele Huf, Jacob Alexander, Pinky Gandhi, Michael H Allen

https://doi.org/10.1002/14651858.CD005146.pub3

2009 Jul 08

Haloperidol plus promethazine for psychosis‐induced aggression

Review

Gisele Huf, Jacob Alexander, Michael H Allen, Nirmal S Raveendran

https://doi.org/10.1002/14651858.CD005146.pub2

2004 Oct 18

Haloperidol plus promethazine for psychosis‐induced aggression

Review

Gisele Huf, Jacob Alexander, Michael H Allen, Nirmal S Raveendran

https://doi.org/10.1002/14651858.CD005146

Differences between protocol and review

We consulted Clive E Adams (CEA) regarding the multiple time periods for which data are now available. We wanted to balance maximising the value of the efforts of trialists but not undermine the protocol by presenting data in such a way that promotes multiple and needless analysis. CEA, blind to data, suggested keeping to protocol for the 30‐minute outcomes and adding 1 hour as a time period, as the first 60 minutes are so important clinically. He also suggested presenting data for the longer‐term outcomes 'by > 2 to ≤ 6 hours' as one group. We recognise that this is driven by the trials and was not been pre‐stated in the original protocol. However, we think in this clinical situation the broad category has some meaning, and we did not come to this decision after assimilating the data.

For the 2015 update, we have added some data into a seventh comparison. This was just to ensure that this is the full repository of data from the relevant trial. This comparison contains some extra data at the 40‐minute stage that does not materially change any part of the review.

We have updated some methods to reflect current methodology of the Cochrane Schizophrenia Group. We moved the outcome 'specific behaviour' down the secondary outcomes list.

Keywords

MeSH

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Haloperidol structure.
Figures and Tables -
Figure 1

Haloperidol structure.

Promethazine structure.
Figures and Tables -
Figure 2

Promethazine structure.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 4

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Study flow diagram 2015 update.
Figures and Tables -
Figure 5

Study flow diagram 2015 update.

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 1 Tranquil or asleep: 1. Not tranquil or asleep.
Figures and Tables -
Analysis 1.1

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 1 Tranquil or asleep: 1. Not tranquil or asleep.

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 2 Tranquil or asleep: 2. Not asleep.
Figures and Tables -
Analysis 1.2

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 2 Tranquil or asleep: 2. Not asleep.

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 3 Tranquil or asleep: 3. Time until tranquil or asleep (RSS, high score=good).
Figures and Tables -
Analysis 1.3

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 3 Tranquil or asleep: 3. Time until tranquil or asleep (RSS, high score=good).

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 4 Global state: 1. Needing restraints or seclusion.
Figures and Tables -
Analysis 1.4

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 4 Global state: 1. Needing restraints or seclusion.

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 5 Global state: 2. Various measures.
Figures and Tables -
Analysis 1.5

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 5 Global state: 2. Various measures.

Study

Intervention

Mean

SD

Total

Baldacara 2011

Haloperidol + Promethazine

1.10

1.03

30

Baldacara 2011

Haloperidol

1.53

1.19

30

Figures and Tables -
Analysis 1.6

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 6 Global state: 3. Average value of additional medication ‐ after initial dose (skewed data).

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 7 Adverse effects: 1. General ‐ Any serious adverse effect.
Figures and Tables -
Analysis 1.7

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 7 Adverse effects: 1. General ‐ Any serious adverse effect.

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 8 Adverse effects: 2. Specific ‐ a. Cardiovascular ‐ hypotension.
Figures and Tables -
Analysis 1.8

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 8 Adverse effects: 2. Specific ‐ a. Cardiovascular ‐ hypotension.

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 9 Adverse effects: 2. Specific ‐ b. Central Nervous System.
Figures and Tables -
Analysis 1.9

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 9 Adverse effects: 2. Specific ‐ b. Central Nervous System.

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 10 Adverse effects: 2. Specific ‐ c. Extrapyramidal problems.
Figures and Tables -
Analysis 1.10

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 10 Adverse effects: 2. Specific ‐ c. Extrapyramidal problems.

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 11 Service outcomes: Not discharged ‐ by 2 weeks.
Figures and Tables -
Analysis 1.11

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 11 Service outcomes: Not discharged ‐ by 2 weeks.

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 12 Specific behaviour: 1. Aggression ‐ a. Other episode of agression.
Figures and Tables -
Analysis 1.12

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 12 Specific behaviour: 1. Aggression ‐ a. Other episode of agression.

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 13 Specific behaviour: 1. Aggression ‐ b. Average aggression score (OAS ,high score=bad).
Figures and Tables -
Analysis 1.13

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 13 Specific behaviour: 1. Aggression ‐ b. Average aggression score (OAS ,high score=bad).

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 14 Specific behaviour: 1. Aggression ‐ c. Average agitation score (OASS, high score=bad).
Figures and Tables -
Analysis 1.14

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 14 Specific behaviour: 1. Aggression ‐ c. Average agitation score (OASS, high score=bad).

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 15 Leaving the study early.
Figures and Tables -
Analysis 1.15

Comparison 1 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL, Outcome 15 Leaving the study early.

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 1 Tranquil or asleep: 1. Not tranquil or asleep.
Figures and Tables -
Analysis 2.1

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 1 Tranquil or asleep: 1. Not tranquil or asleep.

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 2 Tranquil or asleep: 2. Not asleep.
Figures and Tables -
Analysis 2.2

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 2 Tranquil or asleep: 2. Not asleep.

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 3 Tranquil or asleep: 3. Never tranquil or asleep during first 4 hours.
Figures and Tables -
Analysis 2.3

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 3 Tranquil or asleep: 3. Never tranquil or asleep during first 4 hours.

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 4 Tranquil or asleep: 4. Average sedation score (RSS, high score=good).
Figures and Tables -
Analysis 2.4

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 4 Tranquil or asleep: 4. Average sedation score (RSS, high score=good).

Study

Intervention

Mean (mins)

SD

N

Statistical test

p

time until tranquil or asleep

TREC‐Vellore‐II

Haloperidol + Promethazine

12.8

16.7

150

Mann‐Whitney U

0.4

TREC‐Vellore‐II

Olanzapine

20.5

34.5

150

time until asleep

TREC‐Vellore‐II

Haloperidol + Promethazine

26.2

32.2

150

Mann‐Whitney U

0.2

TREC‐Vellore‐II

Olanzapine

34.9

42.2

150

Figures and Tables -
Analysis 2.5

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 5 Tranquil or asleep: 5. Time (skewed data).

Study

Intervention

Mean

SD

N

at 30 minutes

Mantovani 2013

Haloperidol + Promethazine

10.9

6.7

27

Mantovani 2013

Olanzapine

10.1

6.4

25

at 60 minutes

Mantovani 2013

Haloperidol + Promethazine

11.1

7.6

27

Mantovani 2013

Olanzapine

8

3.8

25

at 90 minutes

Mantovani 2013

Haloperidol + Promethazine

10.7

6.7

27

Mantovani 2013

Olanzapine

9.2

5.3

25

Figures and Tables -
Analysis 2.6

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 6 Tranquil or asleep: 6. Effect of tranquillisation (PANSS‐EC, high=bad) (skewed data).

Study

Intervention

Mean

SD

Nl

at 30 minutes

Mantovani 2013

Haloperidol + Promethazine

5.2

8.1

27

Mantovani 2013

Olanzapine

5.5

7.5

25

at 90 minutes

Mantovani 2013

Haloperidol + Promethazine

5.0

10.8

27

Mantovani 2013

Olanzapine

5.8

10

25

Figures and Tables -
Analysis 2.7

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 7 Tranquil or asleep: 7. Level of tranquillisation / agitation (ACES) (skewed data).

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 8 Global state: 1. No overall improvement.
Figures and Tables -
Analysis 2.8

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 8 Global state: 1. No overall improvement.

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 9 Global state: 2. Needing restraints or seclusion.
Figures and Tables -
Analysis 2.9

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 9 Global state: 2. Needing restraints or seclusion.

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 10 Global state: 3. Various measures.
Figures and Tables -
Analysis 2.10

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 10 Global state: 3. Various measures.

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 11 Global state: 4. Average improvement (CGI, high score=bad).
Figures and Tables -
Analysis 2.11

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 11 Global state: 4. Average improvement (CGI, high score=bad).

Study

Intervention

Mean

SD

N

Baldacara 2011

Haloperidol + Promethazine

1.10

1.03

30

Baldacara 2011

Olanzapine

0.37

0.77

30

Figures and Tables -
Analysis 2.12

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 12 Global state: 5. Average value of additional medication ‐ after initial dose (skewed data).

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 13 Adverse effects: 1. General ‐ Serious adverse effect.
Figures and Tables -
Analysis 2.13

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 13 Adverse effects: 1. General ‐ Serious adverse effect.

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 14 Adverse effects: 2. Specific ‐ a. Cardiovascular ‐ hypotension.
Figures and Tables -
Analysis 2.14

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 14 Adverse effects: 2. Specific ‐ a. Cardiovascular ‐ hypotension.

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 15 Adverse effects: 2. Specific ‐ b. Central Nervous System ‐ sedation ‐ excessive.
Figures and Tables -
Analysis 2.15

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 15 Adverse effects: 2. Specific ‐ b. Central Nervous System ‐ sedation ‐ excessive.

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 16 Adverse effects: 2. Specific ‐ c. Extrapyramidal problems ‐ 0‐4 hours.
Figures and Tables -
Analysis 2.16

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 16 Adverse effects: 2. Specific ‐ c. Extrapyramidal problems ‐ 0‐4 hours.

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 17 Specific behaviour: 1. Severe agitation.
Figures and Tables -
Analysis 2.17

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 17 Specific behaviour: 1. Severe agitation.

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 18 Specific behaviour: 2. Average aggression score (OAS, high score=bad).
Figures and Tables -
Analysis 2.18

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 18 Specific behaviour: 2. Average aggression score (OAS, high score=bad).

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 19 Specific behaviour: 3. Average agitation score (OASS, high score=bad).
Figures and Tables -
Analysis 2.19

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 19 Specific behaviour: 3. Average agitation score (OASS, high score=bad).

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 20 Service outcomes.
Figures and Tables -
Analysis 2.20

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 20 Service outcomes.

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 21 Leaving the study early.
Figures and Tables -
Analysis 2.21

Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 21 Leaving the study early.

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 1 Tranquil or asleep: 1. Average sedation score (RSS, high score=good).
Figures and Tables -
Analysis 3.1

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 1 Tranquil or asleep: 1. Average sedation score (RSS, high score=good).

Study

Intervention

Mean

SD

N

at 30 minutes

Mantovani 2013

Haloperidol + Promethazine

10.9

6.7

27

Mantovani 2013

Ziprasidone

12.6

9.1

23

at 60 minutes

Mantovani 2013

Haloperidol + Promethazine

11.1

7.6

27

Mantovani 2013

Ziprasidone

10.5

8

23

at 90 minutes

Mantovani 2013

Haloperidol + Promethazine

10.7

9.2

27

Mantovani 2013

Ziprasidone

11.2

8.3

23

Figures and Tables -
Analysis 3.2

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 2 Tranquil or asleep: 2. Effect of tranquilisation (PANSS‐EC, high=bad) (skewed data).

Study

Intervention

Mean

SD

N

at 30 minutes

Mantovani 2013

Haloperidol + Promethazine

5.2

8.1

27

Mantovani 2013

Ziprasidone

4.8

4.6

23

at 90 minutes.

Mantovani 2013

Haloperidol + Promethazine

5.0

10.8

27

Mantovani 2013

Ziprasidone

5.1

6.9

23

Figures and Tables -
Analysis 3.3

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 3 Tranquil or asleep: 3. Level of tranquilisation / agitation (ACES) (skewed data).

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 4 Global state: 1. Needing restraints or seclusion.
Figures and Tables -
Analysis 3.4

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 4 Global state: 1. Needing restraints or seclusion.

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 5 Global state: 2. Additional tranquillising drugs.
Figures and Tables -
Analysis 3.5

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 5 Global state: 2. Additional tranquillising drugs.

Study

Intervention

Mean

SD

N

Baldacara 2011

Haloperidol + Promethazine

1.10

1.03

30

Baldacara 2011

Ziprasidone

0.77

0.98

30

Figures and Tables -
Analysis 3.6

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 6 Global state: 3. Average value of additional medication ‐ after initial dose (skewed data).

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 7 Adverse effects: 1. Specific ‐ a. Cardiovascular ‐ hypotension.
Figures and Tables -
Analysis 3.7

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 7 Adverse effects: 1. Specific ‐ a. Cardiovascular ‐ hypotension.

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 8 Adverse effects: 1. Specific ‐ b. Central Nervous System ‐ excessive sedation.
Figures and Tables -
Analysis 3.8

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 8 Adverse effects: 1. Specific ‐ b. Central Nervous System ‐ excessive sedation.

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 9 Adverse effects: 1. Specific ‐ c. Extrapyramidal problems ‐ 0‐4 hours.
Figures and Tables -
Analysis 3.9

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 9 Adverse effects: 1. Specific ‐ c. Extrapyramidal problems ‐ 0‐4 hours.

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 10 Specific behaviour: 1. Severe agitation.
Figures and Tables -
Analysis 3.10

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 10 Specific behaviour: 1. Severe agitation.

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 11 Specific behaviour: 2. Average aggression score (OAS, high score=bad).
Figures and Tables -
Analysis 3.11

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 11 Specific behaviour: 2. Average aggression score (OAS, high score=bad).

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 12 Specific behaviour: 3. Average agitation score (OASS, high score=bad).
Figures and Tables -
Analysis 3.12

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 12 Specific behaviour: 3. Average agitation score (OASS, high score=bad).

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 13 Leaving the study early.
Figures and Tables -
Analysis 3.13

Comparison 3 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE, Outcome 13 Leaving the study early.

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 1 Tranquil or asleep: 1. Average sedation score (RSS, high score=good).
Figures and Tables -
Analysis 4.1

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 1 Tranquil or asleep: 1. Average sedation score (RSS, high score=good).

Study

Intervention

Mean

SD

N

at 30 minutes

Mantovani 2013

Haloperidol + Promethazine

10.9

6.7

27

Mantovani 2013

Haloperidol + Midazolam

8.7

4.1

25

at 60 minutes

Mantovani 2013

Haloperidol + Promethazine

11.1

7.6

27

Mantovani 2013

Haloperidol + Midazolam

8.8

6.1

25

at 90 minutes

Mantovani 2013

Haloperidol + Promethazine

10.7

9.2

27

Mantovani 2013

Haloperidol + Midazolam

9.4

9.4

25

Figures and Tables -
Analysis 4.2

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 2 Tranquil or asleep: 2. Effect of tranquilisation (PANSS‐EC, high score=bad) (skewed data).

Study

Intervention

Mean

SD

N

at 30 minutes

Mantovani 2013

Haloperidol + Promethazine

5.2

8.1

27

Mantovani 2013

Haloperidol + Midazolam

6

7.5

25

at 90 minutes

Mantovani 2013

Haloperidol + Promethazine

5.0

10.8

27

Mantovani 2013

Haloperidol + Midazolam

5.8

12.5

25

Figures and Tables -
Analysis 4.3

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 3 Tranquil or asleep: 3. Level of tranquilisation / agitation (ACES) (skewed data).

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 4 Global state: 1. Needing restraints or seclusion.
Figures and Tables -
Analysis 4.4

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 4 Global state: 1. Needing restraints or seclusion.

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 5 Global state: 2. Additional tranquilising drugs.
Figures and Tables -
Analysis 4.5

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 5 Global state: 2. Additional tranquilising drugs.

Study

Intervention

Mean

SD

N

Baldacara 2011

Haloperidol + Promethazine

1.10

1.03

30

Baldacara 2011

Haloperidol + Midazolam

1.73

0.87

30

Figures and Tables -
Analysis 4.6

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 6 Global state: 3. Average value of additional medication ‐ after initial dose (skewed data).

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 7 Adverse effects: 1. Specific ‐ a. Cardiovascular ‐ hypotension.
Figures and Tables -
Analysis 4.7

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 7 Adverse effects: 1. Specific ‐ a. Cardiovascular ‐ hypotension.

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 8 Adverse effects: 1. Specific ‐ b. Central Nervous System ‐ excessive sedation.
Figures and Tables -
Analysis 4.8

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 8 Adverse effects: 1. Specific ‐ b. Central Nervous System ‐ excessive sedation.

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 9 Adverse effects: 1. Specific ‐ c. Extrapyramidal problems ‐ 0‐4 hours.
Figures and Tables -
Analysis 4.9

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 9 Adverse effects: 1. Specific ‐ c. Extrapyramidal problems ‐ 0‐4 hours.

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 10 Specific behaviour: 1. Average aggression score (OAS, high score=bad).
Figures and Tables -
Analysis 4.10

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 10 Specific behaviour: 1. Average aggression score (OAS, high score=bad).

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 11 Specific behaviour: 2. Average agitation score (OASS, high score=bad).
Figures and Tables -
Analysis 4.11

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 11 Specific behaviour: 2. Average agitation score (OASS, high score=bad).

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 12 Specific behaviour: 3. Severe agitation.
Figures and Tables -
Analysis 4.12

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 12 Specific behaviour: 3. Severe agitation.

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 13 Leaving the study early.
Figures and Tables -
Analysis 4.13

Comparison 4 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM), Outcome 13 Leaving the study early.

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 1 Tranquil or asleep: 1. Not tranquil or asleep.
Figures and Tables -
Analysis 5.1

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 1 Tranquil or asleep: 1. Not tranquil or asleep.

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 2 Tranquil or asleep: 2. Not asleep.
Figures and Tables -
Analysis 5.2

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 2 Tranquil or asleep: 2. Not asleep.

Study

Intervention

Mean (mins)

SD

N

Statistical test

p

time until tranquil or asleep

TREC‐Vellore‐I

Haloperidol + Promethazine

29.7

35.6

100

Mann‐Whitney U 327.0

<0.001

TREC‐Vellore‐I

Lorazepam

47.8

46.7

100

time until asleep

TREC‐Vellore‐I

Haloperidol + Promethazine

37.4

42.9

100

Mann‐Whitney U 1893.5

<0.001

TREC‐Vellore‐I

Lorazepam

80.6

64.3

100

Figures and Tables -
Analysis 5.3

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 3 Tranquil or asleep: 3. Time (skewed data).

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 4 Global state: 1. No overall improvement.
Figures and Tables -
Analysis 5.4

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 4 Global state: 1. No overall improvement.

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 5 Global state: 2. Needing restraints or seclusion.
Figures and Tables -
Analysis 5.5

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 5 Global state: 2. Needing restraints or seclusion.

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 6 Global state: 3. Additional tranquillising drugs.
Figures and Tables -
Analysis 5.6

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 6 Global state: 3. Additional tranquillising drugs.

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 7 Global state: 4. Various measures.
Figures and Tables -
Analysis 5.7

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 7 Global state: 4. Various measures.

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 8 Global state: 5. Average improvement (CGI, high score=bad) ).
Figures and Tables -
Analysis 5.8

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 8 Global state: 5. Average improvement (CGI, high score=bad) ).

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 9 Adverse effects: 1. General ‐ serious adverse effect.
Figures and Tables -
Analysis 5.9

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 9 Adverse effects: 1. General ‐ serious adverse effect.

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 10 Adverse effects: 2. Specific ‐ Extrapyramidal problems ‐ 0‐4 hours.
Figures and Tables -
Analysis 5.10

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 10 Adverse effects: 2. Specific ‐ Extrapyramidal problems ‐ 0‐4 hours.

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 11 Service outcomes: Not discharged.
Figures and Tables -
Analysis 5.11

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 11 Service outcomes: Not discharged.

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 12 Leaving the study early.
Figures and Tables -
Analysis 5.12

Comparison 5 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM, Outcome 12 Leaving the study early.

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 1 Tranquil or asleep: 1. Not tranquil or asleep.
Figures and Tables -
Analysis 6.1

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 1 Tranquil or asleep: 1. Not tranquil or asleep.

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 2 Tranquil or asleep: 2. Not asleep.
Figures and Tables -
Analysis 6.2

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 2 Tranquil or asleep: 2. Not asleep.

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 3 Global state: 1. Needing restraints or seclusion ‐ by 2hrs.
Figures and Tables -
Analysis 6.3

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 3 Global state: 1. Needing restraints or seclusion ‐ by 2hrs.

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 4 Global state: 2. Needing addition drugs during initial phase ‐ by 2hrs.
Figures and Tables -
Analysis 6.4

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 4 Global state: 2. Needing addition drugs during initial phase ‐ by 2hrs.

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 5 Global state: 3. Various measures.
Figures and Tables -
Analysis 6.5

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 5 Global state: 3. Various measures.

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 6 Adverse effects: Serious adverse effect.
Figures and Tables -
Analysis 6.6

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 6 Adverse effects: Serious adverse effect.

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 7 Service outcomes: Not discharged.
Figures and Tables -
Analysis 6.7

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 7 Service outcomes: Not discharged.

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 8 Specific Behaviours: 1. Aggression. a ‐ other episode of aggression ‐ by 24 hrs.
Figures and Tables -
Analysis 6.8

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 8 Specific Behaviours: 1. Aggression. a ‐ other episode of aggression ‐ by 24 hrs.

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 9 Leaving the study early.
Figures and Tables -
Analysis 6.9

Comparison 6 HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM, Outcome 9 Leaving the study early.

Comparison 7 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL ‐ additional 40 minutes data, Outcome 1 Tranquil or asleep: 1. Not tranquil or asleep.
Figures and Tables -
Analysis 7.1

Comparison 7 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL ‐ additional 40 minutes data, Outcome 1 Tranquil or asleep: 1. Not tranquil or asleep.

Comparison 7 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL ‐ additional 40 minutes data, Outcome 2 Tranquil or asleep: 2. Not asleep.
Figures and Tables -
Analysis 7.2

Comparison 7 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL ‐ additional 40 minutes data, Outcome 2 Tranquil or asleep: 2. Not asleep.

Table 3. Included or excluded studies and Cochrane reviews

Study tag

Participants ‐ people with schizophrenia

Relevant Cochrane reviews

+ additional problems

‐ not specifically aggressive/agitated

‐ aggressive/agitated

Comparison

Comparison

Intervention #1

Intervention #2

Intervention #1

Intervention #2

Baldacara 2011

+ none specified

Not applicable

Haloperidol

Haloperidol + midazolam

Gillies 2013; Powney 2012

Olanzapine

Powney 2012

Ziprasidone

Powney 2012

Hou 2011

Risperidone + lorazepam

Gillies 2013; Powney 2012

Baldacara 2011, Mantovani 2013

Haloperidol + midazolam

Olanzapine

Gillies 2013; Powney 2012

Ziprasidone

Gillies 2013; Powney 2012

Srinath 2010

Haloperidol + promethazine

Lorazepam

Gillies 2013; Powney 2012

Baldacara 2011, Mantovani 2013

Olanzapine

Ziprasidone

Belgamwar 2005

Levin 1959

Chlorpromazine

Phenobarbital

Not applicable

Placebo

Adams 2014

Promethazine

Bender 2003

Perazine

Trimipramine

Levin 1959

Phenobarbital

Placebo

Promethazine

Phenobarbital

Placebo

Merlo 2002

Risperidone (2 mg)

Risperidone (4 mg)

Li 2009

Brannen 1969

Trifluoperazine

Placebo

Koch 2014

St. Jean 1967

+ “mental deficiency" [? learning disability]

Chlorpromazine

Periciazine

Yagi 1973

+ drug‐induced parkinsonism/EPS

Mazaticol hydrochloride

Promethazine

Trihexyphenidyl

Otsuka 1978

Methixene

Promethazine

Trihexyphenidyl

Itoh 1972

Piroheptine

Promethazine

Trihexyphenidyl

Perenyi 1989

Procyclidine

Promethazine

Essali 2013

St. Jean 1964

Promethazine

Placebo

Otsuka 1978, Itoh 1972, Yagi 1973

+ drug‐induced parkinsonism/EPS

Promethazine

Trihexyphenidyl

Claveria 1975

+ tardive dyskinesia

Pimozide

Placebo

Mothi 2013

Yang 1999

Promethazine

EPS: extrapyramidal symptoms

Figures and Tables -
Table 3. Included or excluded studies and Cochrane reviews
Table 4. Design of a future study

Methods

Allocation: randomised (clearly described).
Blinding: single blind (outcomes assessor).
Duration: up to 2 weeks.
Design: parallel.
Setting: emergency settings

Participants

Diagnosis: anyone whose aggressive behaviour is thought to be due to psychotic illness.

N=300.
Age: > 18 years.
Sex: N/A.
Inclusion criteria: other measures failed.
Exclusion criteria: specific contra‐indication to evaluated treatments

Interventions

1. Drug intervention of choice. N=150.

2. Drug intervention of choice. N=150.

Both drugs should be known to be effective, but the comparative effectiveness is unclear

Outcomes

Tranquil/asleep: binary outcomes, time.

Behaviour: need for additional medication, additional aggressive episode.

Adverse events.

Acceptability of treatment.

Costs: cost of services, cost of care.

Service outcomes: days in hospital, discharged, transfer to secure unit

Figures and Tables -
Table 4. Design of a future study
Summary of findings for the main comparison. HALOPERIDOL + PROMETHAZINE compared to ANTIPSYCHOTIC ‐ HALOPERIDOL for psychosis‐induced aggression

HALOPERIDOL + PROMETHAZINE compared to ANTIPSYCHOTIC ‐ HALOPERIDOL for psychosis‐induced aggression

Patient or population: people with psychosis‐induced aggression
Settings:
Intervention: HALOPERIDOL + PROMETHAZINE
Comparison: ANTIPSYCHOTIC ‐ HALOPERIDOL

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

ANTIPSYCHOTIC ‐ HALOPERIDOL

HALOPERIDOL + PROMETHAZINE

Tranquil or asleep: Not tranquil or asleep ‐ by 30 minutes

Moderate1

RR 0.65
(0.49 to 0.87)

316
(1 study)

⊕⊕⊕⊕
high

500 per 1000

325 per 1000
(245 to 435)

Global state:
Needing restraints or seclusion by 12 hours

Moderate1

RR 0.83
(0.28 to 2.44)

60
(1 study)

⊕⊕⊝⊝
low2,3

200 per 1000

166 per 1000
(56 to 488)

Adverse effects: Specific and serious adverse effects by 24 hours (not death)
Central nervous system ‐ seizure

Moderate1

RR 0.95
(0.06 to 15.01)

298
(1 study)

⊕⊕⊝⊝
low4,5

10 per 1000

9 per 1000
(1 to 150)

Adverse effect: Specific and serious ‐ Death

See comment

See comment

Not estimable

0
(0)

See comment

No study reported this outcome

Service outcomes: Not discharged ‐ by 2 weeks

Moderate1

RR 0.83
(0.64 to 1.07)

310
(1 study)

⊕⊕⊕⊕
high

500 per 1000

415 per 1000
(320 to 535)

Specific behaviours: Average aggression score ‐ by 12 hours
Overt Aggression Scale

The mean specific behaviours: average aggression score in the intervention groups was
1.8 lower
(1.93 to 1.67 lower)

60
(1 study)

⊕⊕⊝⊝
low3,6

Economics: Costs of care

See comment

See comment

Not estimable

0
(0)

See comment

No study reported this outcome

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Moderate control risk approximates to that of the included trial(s).
2Indirectness: rated 'serious' ‐ pre‐stated outcome was 'another episode of aggression' ‐ proxy outcome used.
3Imprecision: rated 'serious' ‐ sample size is small and confidence intervals wide.
4Indirectedness: rated 'serious' ‐ pre‐stated outcome was 'serious adverse event' ‐ proxy outcome used.
5Imprecision: rated 'serious' ‐ wide confidence intervals ‐ rare events.
6Indirectedness: rated 'serious' ‐ pre‐stated outcome was 'specific behaviours' ‐ proxy outcome used.

Figures and Tables -
Summary of findings for the main comparison. HALOPERIDOL + PROMETHAZINE compared to ANTIPSYCHOTIC ‐ HALOPERIDOL for psychosis‐induced aggression
Summary of findings 2. HALOPERIDOL + PROMETHAZINE compared to ANTIPSYCHOTIC ‐ OLANZAPINE for psychosis‐induced aggression

HALOPERIDOL + PROMETHAZINE compared to ANTIPSYCHOTIC ‐ OLANZAPINE for psychosis‐induced aggression

Patient or population: people with psychosis‐induced aggression
Settings:
Intervention: HALOPERIDOL + PROMETHAZINE
Comparison: ANTIPSYCHOTIC ‐ OLANZAPINE

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

ANTIPSYCHOTIC ‐ OLANZAPINE

HALOPERIDOL + PROMETHAZINE

Tranquil or asleep: Not tranquil or asleep ‐ by 30 mins

Moderate1

RR 0.60
(0.22 to 1.61)

300
(1 study)

⊕⊕⊕⊕
high

100 per 1000

60 per 1000
(22 to 161)

Global state:
Needing restraints or seclusion by 12 hours

Moderate

RR 5.00
(0.62 to 40.28)

60
(1 study)

⊕⊕⊝⊝
low2,3

50 per 10001

250 per 1000
(31 to 1000)

Adverse effects: Specific and serious adverse effects by 24 hours
Central nervous system ‐ excessive sedation.

Moderate

RR 0.67
(0.12 to 3.84)

116
(2 studies)

⊕⊕⊝⊝
low4,5

100 per 10001

64 per 1000
(11 to 364)

Adverse effect: Specific ‐ Death

See comment

See comment

Not estimable

0
(0)

See comment

No study reported this outcome

Service outcomes: Not discharged ‐ by 4 hours

Moderate

RR 0.94
(0.77 to 1.16)

300
(1 study)

⊕⊕⊕⊕
high

600 per 10001

564 per 1000
(462 to 696)

Specific behaviours: Average aggression score ‐ by 12 hours
Overt Aggression Scale

The mean specific behaviours: average aggression score in the intervention groups was
2 lower
(2.21 to 1.79 lower)

60
(1 study)

⊕⊕⊝⊝
low5,6

Economics: Costs of care7

See comment

See comment

Not estimable

0
(0)

See comment

No study reported this outcome

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Moderate control risk approximates to that of the included trial(s).
2Indirectness: rated 'serious' ‐ pre‐stated outcome was 'another episode of aggression' ‐ proxy outcome used.
3Imprecision: rated 'serious' as sample size too small and confidence interval too wide.
4Indirectness: rated 'serious' ‐ pre‐stated outcome was 'serious adverse effect' ‐ proxy outcome used.
5Imprecision: rated 'serious' ‐ sample size too small and confidence interval wide.
6Indirectness: rated 'serious' ‐ pre‐stated outcome was 'specific behaviours' ‐ proxy outcome used.

Figures and Tables -
Summary of findings 2. HALOPERIDOL + PROMETHAZINE compared to ANTIPSYCHOTIC ‐ OLANZAPINE for psychosis‐induced aggression
Summary of findings 3. HALOPERIDOL + PROMETHAZINE compared to ANTIPSYCHOTIC ‐ ZIPRASIDONE for psychosis‐induced aggression

HALOPERIDOL + PROMETHAZINE compared to ANTIPSYCHOTIC ‐ ZIPRASIDONE for psychosis‐induced aggression

Patient or population: people with psychosis‐induced aggression
Settings:
Intervention: HALOPERIDOL + PROMETHAZINE
Comparison: ANTIPSYCHOTIC ‐ ZIPRASIDONE

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

ANTIPSYCHOTIC ‐ ZIPRASIDONE

HALOPERIDOL + PROMETHAZINE

Tranquil or asleep: Average sedation score ‐ by 30 minutes
Ramsay Sedation Scale

The mean tranquil or asleep: average sedation score in the intervention groups was
0.1 lower
(0.58 lower to 0.38 higher)

60
(1 study)

⊕⊕⊝⊝
low1,2

Global state: Needing restraints or seclusion ‐ by 12 hours

Moderate

RR 0.5
(0.19 to 1.29)

60
(1 study)

⊕⊕⊕⊝
moderate4

400 per 10003

200 per 1000
(76 to 516)

Adverse effects: Specific and serious adverse effect ‐ by 24 hours
Central nervous system ‐ excessive sedation.

Moderate

RR 0.30
(0.06 to 1.43)

111
(2 studies)

⊕⊕⊝⊝
low2,5

150 per 10003

47 per 1000
(11 to 219)

Adverse effect: Specific ‐ Death

See comment

See comment

Not estimable

0
(0)

See comment

No study reported this outcome

Service outcomes: Not discharged ‐ by 2 weeks

See comment

See comment

Not estimable

0
(0)

See comment

No study reported this outcome

Specific behaviours: Average aggression score ‐ by 12 hours
Overt Aggression Scale

The mean specific behaviours: average aggression score in the intervention groups was
1.6 lower
(1.75 to 1.45 lower)

60
(1 study)

⊕⊕⊕⊝
moderate2,4

Economics: Costs of care

See comment

See comment

Not estimable

0
(0)

See comment

No study reported this outcome

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Indirectness: rated 'serious' ‐ pre‐stated outcome 'Tranquil or asleep' ‐ proxy outcome used.
2Imprecision: rated 'serious' ‐ sample size small.
3Moderate control risk approximates to that of the included trial.
4Indirectness: rated 'serious' ‐ pre‐stated outcome 'another episode of aggression' ‐ proxy outcome used.
5Indirectness: rated 'serious' ‐ pre‐stated outcome 'serious adverse effect' ‐ proxy outcome used.

Figures and Tables -
Summary of findings 3. HALOPERIDOL + PROMETHAZINE compared to ANTIPSYCHOTIC ‐ ZIPRASIDONE for psychosis‐induced aggression
Summary of findings 4. HALOPERIDOL + PROMETHAZINE compared to ANTIPSYCHOTIC & BENZODIAZEPINE ‐ HALOPERIDOL + MIDAZOLAM for psychosis‐induced aggression

HALOPERIDOL + PROMETHAZINE compared to ANTIPSYCHOTIC & BENZODIAZEPINE ‐ HALOPERIDOL + MIDAZOLAM for psychosis‐induced aggression

Patient or population: people with psychosis‐induced aggression
Settings:
Intervention: HALOPERIDOL + PROMETHAZINE
Comparison: ANTIPSYCHOTIC & BENZODIAZEPINE ‐ HALOPERIDOL + MIDAZOLAM

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

ANTIPSYCHOTIC & BENZODIAZEPINE ‐ HALOPERIDOL + MIDAZOLAM

HALOPERIDOL + PROMETHAZINE

Tranquil or asleep: Average sedation score ‐ by 1 hour
Ramsay Sedation Scale

The mean tranquil or asleep: average sedation score in the intervention groups was
0.6 lower
(1.13 to 0.07 lower)

60
(1 study)

⊕⊕⊝⊝
low1

Global state: Needing restraints or seclusion ‐ by 12 hours

Moderate

RR 0.24
(0.1 to 0.55)

60
(1 study)

See comment

700 per 10002

168 per 1000
(70 to 385)

Adverse effects: Specific and serious adverse effect ‐ by 24 hours
Central nervous system ‐ excessive sedation

Moderate

RR 0.12
(0.03 to 0.49)

117
(2 studies)

⊕⊕⊝⊝
low3,4

300 per 10002

33 per 1000
(9 to 141)

Adverse effect: Specific ‐ Death

See comment

See comment

Not estimable

0
(0)

See comment

No study reported this outcome

Service outcomes: Not discharged ‐ by 2 weeks

See comment

See comment

Not estimable

0
(0)

See comment

No study reported this outcome

Specific behaviours: Average aggression score ‐ by 12 hours
Overt Aggression Scale

The mean specific behaviours: average aggression score in the intervention groups was
3.7 lower
(4.39 to 3.01 lower)

60
(1 study)

See comment

Economics: Costs of care

See comment

See comment

Not estimable

0
(0)

See comment

No study reported this outcome

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Indirectness: rated 'serious' ‐ pre‐stated outcome 'tranquil or asleep' ‐ proxy outcome used.
2Moderate control risk approximates to that of the included trial.
3Indirectness: rated 'serious' ‐ pre‐stated outcome was 'another episode of aggression' ‐ proxy outcome used.
4Imprecision: rated 'serious' ‐ sample size small.

Figures and Tables -
Summary of findings 4. HALOPERIDOL + PROMETHAZINE compared to ANTIPSYCHOTIC & BENZODIAZEPINE ‐ HALOPERIDOL + MIDAZOLAM for psychosis‐induced aggression
Summary of findings 5. HALOPERIDOL + PROMETHAZINE compared to BENZODIAZEPINES ‐ LORAZEPAM for psychosis‐induced aggression

HALOPERIDOL + PROMETHAZINE compared to BENZODIAZEPINES ‐ LORAZEPAM for psychosis‐induced aggression

Patient or population: people with psychosis‐induced aggression
Settings:
Intervention: HALOPERIDOL + PROMETHAZINE
Comparison: BENZODIAZEPINES ‐ LORAZEPAM

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

BENZODIAZEPINES ‐ LORAZEPAM

HALOPERIDOL + PROMETHAZINE

Tranquil or asleep: Not tranquil or asleep ‐ by 30 mins
Follow‐up: to 30 minutes

Moderate

RR 0.26
(0.1 to 0.68)

200
(1 study)

⊕⊕⊕⊕
high

200 per 10001

52 per 1000
(20 to 136)

Global state: Needing restraints or seclusion ‐ by 12 hours

Moderate

RR 0.82
(0.35 to 1.89)

200
(1 study)

⊕⊕⊕⊝
moderate2

150 per 10001

123 per 1000
(52 to 283)

Adverse effects: Specific and serious adverse effect ‐ by 24 hours
Central nervous system ‐ excessive sedation

See comment

Not estimable

0
(0)

See comment

No study reported for this outcome

Adverse effect: Specific ‐ Death

See comment

Not estimable

0
(0)

See comment

No study reported for this outcome

Service outcomes: Not discharged ‐ by 4 hours

Moderate

RR 1.13
(0.85 to 1.5)

200
(1 study)

⊕⊕⊕⊕
high

500 per 10001

565 per 1000
(425 to 750)

Specific behaviours: Average aggression score

See comment

See comment

Not estimable

0
(0)

See comment

No study reported for this outcome

Economics: Costs of care

See comment

See comment

Not estimable

0
(0)

See comment

No study reported for this outcome

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Moderate control risk approximates to that of the included trial.
2Indirectness: rated 'serious' ‐ pre‐stated outcome was 'another episode of aggression' ‐ proxy outcome used.
3Imprecision: rated 'serious' ‐ confidence interval is wide.

Figures and Tables -
Summary of findings 5. HALOPERIDOL + PROMETHAZINE compared to BENZODIAZEPINES ‐ LORAZEPAM for psychosis‐induced aggression
Summary of findings 6. HALOPERIDOL + PROMETHAZINE compared to BENZODIAZEPINES ‐ MIDAZOLAM for psychosis‐induced aggression

HALOPERIDOL + PROMETHAZINE compared to BENZODIAZEPINES ‐ MIDAZOLAM for psychosis‐induced aggression

Patient or population: people with psychosis‐induced aggression
Settings:
Intervention: HALOPERIDOL + PROMETHAZINE
Comparison: BENZODIAZEPINES ‐ MIDAZOLAM

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

Assumed risk

Corresponding risk

BENZODIAZEPINES ‐ MIDAZOLAM

HALOPERIDOL + PROMETHAZINE

Tranquil or asleep: Not tranquil or asleep
Follow‐up: to 30 minutes

Moderate

RR 2.9
(1.75 to 4.8)

301
(1 study)

⊕⊕⊕⊕
high

200 per 10001

580 per 1000
(350 to 960)

Global state: Needing restraints or seclusion‐ by 2 hours

Moderate

RR 1.22
(0.82 to 1.82)

301
(1 study)

⊕⊕⊕⊝
moderate2

250 per 10001

305 per 1000
(205 to 455)

Adverse effect: Specific ‐ Death

See comment

See comment

Not estimable

0
(0)

See comment

No study reported for this outcome

Service outcomes: Not discharged ‐
Follow‐up: to 2 weeks

Moderate

RR 1.05
(0.84 to 1.29)

301
(1 study)

⊕⊕⊕⊕
high

550 per 10001

577 per 1000
(462 to 709)

Specific behavioursAggression
Follow‐up: to 12 hours

Moderate

RR 0.89
(0.62 to 1.29)

301
(1 study)

⊕⊕⊕⊝
moderate4

Economics: Costs of care

See comment

See comment

Not estimable

0
(0)

See comment

No study reported for this outcome

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Moderate control risk approximates to that of the included trial.
2Indirectness: rated 'serious' ‐ pre‐stated outcome was 'another episode of aggression' ‐ proxy outcome used.
3Imprecision: rated 'serious' ‐ confidence interval wide.
4Indirectness: rated 'serious' ‐ pre‐stated outcome was 'specific behaviours' ‐ proxy outcome used.

Figures and Tables -
Summary of findings 6. HALOPERIDOL + PROMETHAZINE compared to BENZODIAZEPINES ‐ MIDAZOLAM for psychosis‐induced aggression
Table 1. Survey of rapid tranquillisation in Rio de Janeiro 2002

Drug of choice

Frequency of use

mean mg (range)

Haloperidol + promethazine

61%

5 (2.5 to 10) + 50 (25 to 100)

Haloperidol + promethazine + diazepam

15%

5 (2.5 to 10) + 50 (25 to 100) + 10

Diazepam

9%

10

Haloperidol + promethazine + chlorpromazine

7%

5 + 50 + 25

Chlorpromazine + diazepam + promethazine

1%

25 + 10 + 50

Chlorpromazine + promethazine

1%

25 + 50

Chlorpromazine

1%

25

Diazepam + promethazine

1%

10 + 50

Haloperidol + diazepam

1%

5 + 10

Promethazine

1%

50

Figures and Tables -
Table 1. Survey of rapid tranquillisation in Rio de Janeiro 2002
Table 2. Other relevant Cochrane reviews

Focus of review

Reference

Completed and maintained reviews

'As required' medication regimens for seriously mentally ill people in hospital

Chakrabarti 2007

Benzodiazepines for psychosis‐induced aggression or agitation

Gillies 2005

Chlorpromazine for psychosis‐induced aggression or agitation

Ahmed 2010

Clotiapine for acute psychotic illnesses

Berk 2004

Containment strategies for people with serious mental illness

Muralidharan 2006

Droperidol for acute psychosis

Rathbone 2004

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

Powney 2012

Olanzapine IM or velotab for acutely disturbed/agitated people with suspected serious mental illnesses

Belgamwar 2005

Seclusion and restraint for serious mental illnesses

Sailas 2000

Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses

Gibson 2004

Reviews in the process of being completed

Risperidone for psychosis‐induced aggression or agitation

Ahmed 2011

Haloperidol for long‐term aggression in psychosis

Khushu 2012

Loxapine inhaler for psychosis‐induced aggression

Vangala 2012

Clozapine for people with schizophrenia and recurrent physical aggression

Toal 2012

Quetiapine for psychosis‐induced aggression or agitation

Wilkie 2012

De‐escalation techniques for psychosis‐induced aggression

Rao 2012

Figures and Tables -
Table 2. Other relevant Cochrane reviews
Comparison 1. HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Tranquil or asleep: 1. Not tranquil or asleep Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 by 30 minutes

1

316

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.49, 0.87]

1.2 by 1 hour

1

316

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.46, 1.23]

1.3 by 2 hours

1

316

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.32, 0.96]

2 Tranquil or asleep: 2. Not asleep Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 by 30 minutes

1

316

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.82, 0.96]

2.2 by 1 hour

1

316

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.84, 1.28]

2.3 by 2 hours

1

316

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.77, 1.31]

3 Tranquil or asleep: 3. Time until tranquil or asleep (RSS, high score=good) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

3.1 by 1 hour

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐0.58, 0.38]

3.2 by 2 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐0.30, 0.50]

3.3 by 4 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.30 [‐0.18, 0.78]

3.4 by 6 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.20 [‐0.08, 0.48]

3.5 by 12 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.28, 0.28]

4 Global state: 1. Needing restraints or seclusion Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 by 2 hours

1

311

Risk Ratio (M‐H, Fixed, 95% CI)

0.80 [0.54, 1.18]

4.2 by 12 hours

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.28, 2.44]

5 Global state: 2. Various measures Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 requiring additional drugs during initial phase ‐ by 2 hours

1

311

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.16, 1.25]

5.2 doctor called to see patient ‐ by 24 hours

1

298

Risk Ratio (M‐H, Fixed, 95% CI)

0.66 [0.44, 0.99]

5.3 refusing oral drugs ‐ at 24 hours

1

294

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.54, 1.97]

6 Global state: 3. Average value of additional medication ‐ after initial dose (skewed data) Show forest plot

Other data

No numeric data

7 Adverse effects: 1. General ‐ Any serious adverse effect Show forest plot

1

298

Risk Ratio (M‐H, Fixed, 95% CI)

0.09 [0.01, 0.66]

7.1 by 24 hours

1

298

Risk Ratio (M‐H, Fixed, 95% CI)

0.09 [0.01, 0.66]

8 Adverse effects: 2. Specific ‐ a. Cardiovascular ‐ hypotension Show forest plot

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

7.0 [0.38, 129.93]

9 Adverse effects: 2. Specific ‐ b. Central Nervous System Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9.1 seizure ‐ by 24 hours

1

298

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.06, 15.01]

9.2 sedation ‐ excessive

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.04, 3.03]

10 Adverse effects: 2. Specific ‐ c. Extrapyramidal problems Show forest plot

2

358

Risk Ratio (M‐H, Fixed, 95% CI)

0.35 [0.14, 0.88]

10.1 acute dystonia ‐ by 24 hours

1

298

Risk Ratio (M‐H, Fixed, 95% CI)

0.05 [0.00, 0.76]

10.2 extrapyramidal problems (unspecified) ‐ 0‐4 hours

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.32, 3.10]

11 Service outcomes: Not discharged ‐ by 2 weeks Show forest plot

1

310

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.64, 1.07]

12 Specific behaviour: 1. Aggression ‐ a. Other episode of agression Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

12.1 other episode of aggression ‐ by 24 hours

1

298

Risk Ratio (M‐H, Fixed, 95% CI)

1.17 [0.68, 2.01]

13 Specific behaviour: 1. Aggression ‐ b. Average aggression score (OAS ,high score=bad) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

13.1 by 1 hour

1

60

Mean Difference (IV, Fixed, 95% CI)

4.50 [2.72, 6.28]

13.2 by 2 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.70 [‐0.49, 1.89]

13.3 by 4 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.60 [‐0.71, ‐0.49]

13.4 by 6 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐1.1 [‐1.29, ‐0.91]

13.5 by 12 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐1.8 [‐1.93, ‐1.67]

14 Specific behaviour: 1. Aggression ‐ c. Average agitation score (OASS, high score=bad) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

14.1 by 1 hour

1

60

Mean Difference (IV, Fixed, 95% CI)

24.5 [21.68, 27.32]

14.2 by 2 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

9.40 [8.41, 10.39]

14.3 by 4 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

3.80 [3.27, 4.33]

14.4 by 6 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

2.6 [2.13, 3.07]

14.5 by 12 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.80 [0.55, 1.05]

15 Leaving the study early Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

15.1 before treatment

1

316

Risk Ratio (M‐H, Fixed, 95% CI)

1.46 [0.25, 8.63]

15.2 by 24 hours

2

376

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.41, 1.97]

15.3 by 2 weeks

1

316

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.20, 4.76]

Figures and Tables -
Comparison 1. HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL
Comparison 2. HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Tranquil or asleep: 1. Not tranquil or asleep Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 by 30 minutes

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.6 [0.22, 1.61]

1.2 by 1 hour

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.11 [0.01, 0.87]

1.3 by 2 hours

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.44 [0.14, 1.41]

1.4 by 4 hours

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.26, 2.67]

2 Tranquil or asleep: 2. Not asleep Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 by 30 minutes

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.65 [0.46, 0.93]

2.2 by 1 hour

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.59 [0.40, 0.87]

2.3 by 2 hours

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.24 [0.14, 0.41]

2.4 by 4 hours

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.61 [0.44, 0.86]

3 Tranquil or asleep: 3. Never tranquil or asleep during first 4 hours Show forest plot

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.25 [0.03, 2.21]

4 Tranquil or asleep: 4. Average sedation score (RSS, high score=good) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

4.1 by 1 hour

1

60

Mean Difference (IV, Fixed, 95% CI)

0.20 [‐0.26, 0.66]

4.2 by 2 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐0.26, 0.46]

4.3 by 4 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐0.34, 0.54]

4.4 by 6 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐0.15, 0.35]

4.5 by 12 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.23, 0.23]

5 Tranquil or asleep: 5. Time (skewed data) Show forest plot

Other data

No numeric data

5.1 time until tranquil or asleep

Other data

No numeric data

5.2 time until asleep

Other data

No numeric data

6 Tranquil or asleep: 6. Effect of tranquillisation (PANSS‐EC, high=bad) (skewed data) Show forest plot

Other data

No numeric data

6.1 at 30 minutes

Other data

No numeric data

6.2 at 60 minutes

Other data

No numeric data

6.3 at 90 minutes

Other data

No numeric data

7 Tranquil or asleep: 7. Level of tranquillisation / agitation (ACES) (skewed data) Show forest plot

Other data

No numeric data

7.1 at 30 minutes

Other data

No numeric data

7.3 at 90 minutes

Other data

No numeric data

8 Global state: 1. No overall improvement Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

8.1 by 30 minutes

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.36, 0.91]

8.2 by 1 hour

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.4 [0.21, 0.75]

8.3 by 2 hours

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.44 [0.24, 0.79]

8.4 by 4 hours

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.47 [0.22, 1.01]

9 Global state: 2. Needing restraints or seclusion Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9.1 by 30 minutes

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

1.02 [0.71, 1.47]

9.2 by 1 hour

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.66, 1.44]

9.3 by 2 hours

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.51, 1.25]

9.4 by 4 hours

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.63 [0.34, 1.14]

9.5 by 12 hours

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

5.0 [0.62, 40.28]

10 Global state: 3. Various measures Show forest plot

2

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

10.1 requiring additional drugs during initial phase ‐ by 4 hours

2

356

Risk Ratio (M‐H, Fixed, 95% CI)

0.52 [0.37, 0.74]

10.2 requiring further observation ‐ by 4 hours

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

1.17 [0.80, 1.71]

10.3 doctor called to see patient ‐ by 4 hours

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.47 [0.30, 0.73]

10.4 taking oral drugs ‐ at 2 weeks

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.89, 1.04]

11 Global state: 4. Average improvement (CGI, high score=bad) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

11.1 by 30 minutes

1

300

Mean Difference (IV, Fixed, 95% CI)

‐0.35 [‐0.58, ‐0.12]

11.2 by 1 hour

1

300

Mean Difference (IV, Fixed, 95% CI)

‐0.41 [‐0.60, ‐0.22]

11.3 by 2 hours

1

300

Mean Difference (IV, Fixed, 95% CI)

‐0.36 [‐0.56, ‐0.16]

11.4 by 4 hours

1

300

Mean Difference (IV, Fixed, 95% CI)

‐0.27 [‐0.43, ‐0.11]

12 Global state: 5. Average value of additional medication ‐ after initial dose (skewed data) Show forest plot

Other data

No numeric data

13 Adverse effects: 1. General ‐ Serious adverse effect Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.1 by 4 hours

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.04, 3.17]

13.2 at 2 weeks

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 8.12]

14 Adverse effects: 2. Specific ‐ a. Cardiovascular ‐ hypotension Show forest plot

2

116

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.49, 18.31]

15 Adverse effects: 2. Specific ‐ b. Central Nervous System ‐ sedation ‐ excessive Show forest plot

2

116

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.12, 3.84]

16 Adverse effects: 2. Specific ‐ c. Extrapyramidal problems ‐ 0‐4 hours Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

16.1 any change in scale‐rated extrapyramidal problems (Simpson & Angus Scale)

3

416

Risk Ratio (M‐H, Fixed, 95% CI)

1.76 [1.12, 2.77]

17 Specific behaviour: 1. Severe agitation Show forest plot

1

56

Risk Ratio (M‐H, Fixed, 95% CI)

7.0 [0.38, 129.55]

18 Specific behaviour: 2. Average aggression score (OAS, high score=bad) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

18.1 by 1 hour

1

60

Mean Difference (IV, Fixed, 95% CI)

5.4 [3.72, 7.08]

18.2 by 2 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

1.20 [0.39, 2.01]

18.3 by 4 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.5 [‐0.68, ‐0.32]

18.4 by 6 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐1.20 [‐1.90, ‐0.50]

18.5 by 12 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.00 [‐2.21, ‐1.79]

19 Specific behaviour: 3. Average agitation score (OASS, high score=bad) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

19.1 by 1 hour

1

60

Mean Difference (IV, Fixed, 95% CI)

26.5 [23.76, 29.24]

19.2 by 2 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

13.6 [12.64, 14.56]

19.3 by 4 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

4.0 [3.47, 4.53]

19.4 by 6 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

2.8 [2.31, 3.29]

19.5 by 12 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

1.70 [1.44, 1.96]

20 Service outcomes Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

20.1 admitted ‐ by 4 hours

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.81 [0.56, 1.16]

20.2 not discharged ‐ by 4 hours

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.77, 1.16]

21 Leaving the study early Show forest plot

3

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

21.1 by 30 minutes

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 8.12]

21.2 by 2 hours

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.14 [0.01, 2.74]

21.3 by 4 hours

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.09 [0.01, 1.63]

21.4 by 24 hours

2

116

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.04, 3.01]

21.5 by 2 weeks

1

300

Risk Ratio (M‐H, Fixed, 95% CI)

0.71 [0.33, 1.56]

Figures and Tables -
Comparison 2. HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE
Comparison 3. HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Tranquil or asleep: 1. Average sedation score (RSS, high score=good) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 by 1 hour

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐0.58, 0.38]

1.2 by 2 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐0.36, 0.56]

1.3 by 4 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐0.56, 0.36]

1.4 by 6 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐0.18, 0.38]

1.5 by 12 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐0.38, 0.18]

2 Tranquil or asleep: 2. Effect of tranquilisation (PANSS‐EC, high=bad) (skewed data) Show forest plot

Other data

No numeric data

2.1 at 30 minutes

Other data

No numeric data

2.2 at 60 minutes

Other data

No numeric data

2.3 at 90 minutes

Other data

No numeric data

3 Tranquil or asleep: 3. Level of tranquilisation / agitation (ACES) (skewed data) Show forest plot

Other data

No numeric data

3.1 at 30 minutes

Other data

No numeric data

3.2 at 90 minutes.

Other data

No numeric data

4 Global state: 1. Needing restraints or seclusion Show forest plot

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

0.5 [0.19, 1.29]

5 Global state: 2. Additional tranquillising drugs Show forest plot

1

51

Risk Ratio (M‐H, Fixed, 95% CI)

0.51 [0.19, 1.36]

6 Global state: 3. Average value of additional medication ‐ after initial dose (skewed data) Show forest plot

Other data

No numeric data

7 Adverse effects: 1. Specific ‐ a. Cardiovascular ‐ hypotension Show forest plot

2

111

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.17, 1.75]

8 Adverse effects: 1. Specific ‐ b. Central Nervous System ‐ excessive sedation Show forest plot

2

111

Risk Ratio (M‐H, Fixed, 95% CI)

0.30 [0.06, 1.43]

9 Adverse effects: 1. Specific ‐ c. Extrapyramidal problems ‐ 0‐4 hours Show forest plot

2

111

Risk Ratio (M‐H, Fixed, 95% CI)

1.72 [1.07, 2.76]

10 Specific behaviour: 1. Severe agitation Show forest plot

1

51

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.18, 3.69]

11 Specific behaviour: 2. Average aggression score (OAS, high score=bad) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

11.1 by 1 hour

1

60

Mean Difference (IV, Fixed, 95% CI)

4.50 [2.82, 6.18]

11.2 by 2 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

1.4 [0.55, 2.25]

11.3 by 4 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.30 [‐0.62, 0.02]

11.4 by 6 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.40 [‐0.59, ‐0.21]

11.5 by 12 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐1.60 [‐1.75, ‐1.45]

12 Specific behaviour: 3. Average agitation score (OASS, high score=bad) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

12.1 by 1 hour

1

60

Mean Difference (IV, Fixed, 95% CI)

16.80 [13.68, 19.92]

12.2 by 2 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

5.5 [2.92, 8.08]

12.3 by 4 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.60 [‐1.47, 0.27]

12.4 by 6 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐1.0 [‐1.85, ‐0.15]

12.5 by 12 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐1.90 [‐2.34, ‐1.46]

13 Leaving the study early Show forest plot

2

111

Risk Ratio (M‐H, Fixed, 95% CI)

2.48 [0.11, 58.20]

13.1 by 24 hours

2

111

Risk Ratio (M‐H, Fixed, 95% CI)

2.48 [0.11, 58.20]

Figures and Tables -
Comparison 3. HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ ZIPRASIDONE
Comparison 4. HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Tranquil or asleep: 1. Average sedation score (RSS, high score=good) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

1.1 by 1 hour

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.60 [‐1.13, ‐0.07]

1.2 by 2 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.46, 0.46]

1.3 by 4 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.0 [‐0.51, 0.51]

1.4 by 6 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐0.18, 0.38]

1.5 by 12 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

0.10 [‐0.24, 0.44]

2 Tranquil or asleep: 2. Effect of tranquilisation (PANSS‐EC, high score=bad) (skewed data) Show forest plot

Other data

No numeric data

2.1 at 30 minutes

Other data

No numeric data

2.2 at 60 minutes

Other data

No numeric data

2.3 at 90 minutes

Other data

No numeric data

3 Tranquil or asleep: 3. Level of tranquilisation / agitation (ACES) (skewed data) Show forest plot

Other data

No numeric data

3.1 at 30 minutes

Other data

No numeric data

3.2 at 90 minutes

Other data

No numeric data

4 Global state: 1. Needing restraints or seclusion Show forest plot

1

60

Risk Ratio (M‐H, Fixed, 95% CI)

0.24 [0.10, 0.55]

5 Global state: 2. Additional tranquilising drugs Show forest plot

1

57

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.34, 3.19]

6 Global state: 3. Average value of additional medication ‐ after initial dose (skewed data) Show forest plot

Other data

No numeric data

7 Adverse effects: 1. Specific ‐ a. Cardiovascular ‐ hypotension Show forest plot

2

117

Risk Ratio (M‐H, Fixed, 95% CI)

0.51 [0.16, 1.58]

8 Adverse effects: 1. Specific ‐ b. Central Nervous System ‐ excessive sedation Show forest plot

2

117

Risk Ratio (M‐H, Fixed, 95% CI)

0.12 [0.03, 0.49]

9 Adverse effects: 1. Specific ‐ c. Extrapyramidal problems ‐ 0‐4 hours Show forest plot

2

117

Risk Ratio (M‐H, Fixed, 95% CI)

1.84 [1.12, 3.02]

10 Specific behaviour: 1. Average aggression score (OAS, high score=bad) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

10.1 by 1 hour

1

60

Mean Difference (IV, Fixed, 95% CI)

3.30 [1.35, 5.25]

10.2 by 2 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐1.70 [‐3.46, 0.06]

10.3 by 4 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.70 [‐1.27, ‐0.13]

10.4 by 6 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.70 [‐0.89, ‐0.51]

10.5 by 12 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐3.7 [‐4.39, ‐3.01]

11 Specific behaviour: 2. Average agitation score (OASS, high score=bad) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

11.1 by 1 hour

1

60

Mean Difference (IV, Fixed, 95% CI)

16.00 [13.02, 18.98]

11.2 by 2 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

2.70 [1.67, 3.73]

11.3 by 4 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐1.70 [‐2.79, ‐0.61]

11.4 by 6 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐1.10 [‐2.08, ‐0.12]

11.5 by 12 hours

1

60

Mean Difference (IV, Fixed, 95% CI)

‐10.40 [‐11.47, ‐9.33]

12 Specific behaviour: 3. Severe agitation Show forest plot

1

57

Risk Ratio (M‐H, Fixed, 95% CI)

1.55 [0.28, 8.61]

13 Leaving the study early Show forest plot

2

117

Risk Ratio (M‐H, Fixed, 95% CI)

0.26 [0.03, 2.18]

13.1 by 24 hours

2

117

Risk Ratio (M‐H, Fixed, 95% CI)

0.26 [0.03, 2.18]

Figures and Tables -
Comparison 4. HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC + BENZODIAZEPINE (HALOPERIDOL + MIDAZOLAM)
Comparison 5. HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Tranquil or asleep: 1. Not tranquil or asleep Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 by 30 minutes

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.26 [0.10, 0.68]

1.2 by 1 hour

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.2 [0.04, 0.89]

1.3 by 2 hours

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.25 [0.07, 0.86]

1.4 by 4 hours

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.26, 3.89]

2 Tranquil or asleep: 2. Not asleep Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 by 30 minutes

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.40 [0.29, 0.54]

2.2 by 1 hour

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.49 [0.36, 0.66]

2.3 by 2 hours

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.51 [0.36, 0.71]

2.4 by 4 hours

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.44 [0.30, 0.65]

3 Tranquil or asleep: 3. Time (skewed data) Show forest plot

Other data

No numeric data

3.1 time until tranquil or asleep

Other data

No numeric data

3.2 time until asleep

Other data

No numeric data

4 Global state: 1. No overall improvement Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

4.1 by 30 minutes

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.40 [0.25, 0.66]

4.2 by 1 hour

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.5 [0.32, 0.79]

4.3 by 2 hours

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.46 [0.25, 0.86]

4.4 by 4 hours

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.46, 1.87]

5 Global state: 2. Needing restraints or seclusion Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 by 30 minutes

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.28, 1.09]

5.2 by 1 hour

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.56 [0.27, 1.14]

5.3 by 2 hours

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.35, 1.67]

5.4 by 4 hours

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.35, 1.89]

6 Global state: 3. Additional tranquillising drugs Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 by 30 minutes

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 8.09]

6.2 by 1 hour

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.04, 3.15]

6.3 by 2 hours

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.17, 3.27]

6.4 by 4 hours

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.36, 2.21]

7 Global state: 4. Various measures Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

7.1 doctor called to see patient ‐ by 4 hours

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.72 [0.37, 1.39]

7.2 refusing oral medication ‐ by 2 weeks

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

1.63 [0.70, 3.75]

8 Global state: 5. Average improvement (CGI, high score=bad) ) Show forest plot

1

Mean Difference (IV, Fixed, 95% CI)

Subtotals only

8.1 by 30 minutes

1

200

Mean Difference (IV, Fixed, 95% CI)

‐0.60 [‐0.86, ‐0.34]

8.2 by 1 hour

1

200

Mean Difference (IV, Fixed, 95% CI)

‐0.33 [‐0.54, ‐0.12]

8.3 by 2 hours

1

200

Mean Difference (IV, Fixed, 95% CI)

‐0.23 [‐0.51, 0.05]

8.4 by 4 hours

1

200

Mean Difference (IV, Fixed, 95% CI)

‐0.09 [‐0.32, 0.14]

9 Adverse effects: 1. General ‐ serious adverse effect Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9.1 by 30 minutes

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 8.09]

9.2 by 1 hour

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

9.3 by 2 hours

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

9.4 by 4 hours

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

10 Adverse effects: 2. Specific ‐ Extrapyramidal problems ‐ 0‐4 hours Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

10.1 akathisia (Barnes Akathisia Scale)

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

10.2 any change in scale‐rated extrapyramidal problems (Simpson & Angus Scale)

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

11 Service outcomes: Not discharged Show forest plot

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.85, 1.50]

11.1 by 4 hours

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

1.13 [0.85, 1.50]

12 Leaving the study early Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

12.1 by 4 hours

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.12, 72.77]

12.2 by 2 weeks

1

200

Risk Ratio (M‐H, Fixed, 95% CI)

1.25 [0.51, 3.04]

Figures and Tables -
Comparison 5. HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ LORAZEPAM
Comparison 6. HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Tranquil or asleep: 1. Not tranquil or asleep Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 by 30 minutes

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

2.90 [1.75, 4.80]

1.2 by 1 hour

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

1.91 [0.92, 3.98]

1.3 by 2 hours

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

1.73 [0.70, 4.26]

2 Tranquil or asleep: 2. Not asleep Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 by 30 minutes

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

1.86 [1.48, 2.33]

2.2 by 1 hour

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

2.18 [1.52, 3.12]

2.3 by 2 hours

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

2.13 [1.42, 3.20]

3 Global state: 1. Needing restraints or seclusion ‐ by 2hrs Show forest plot

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

1.22 [0.82, 1.82]

4 Global state: 2. Needing addition drugs during initial phase ‐ by 2hrs Show forest plot

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

3.52 [0.74, 16.69]

5 Global state: 3. Various measures Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

5.1 doctor called to see patient ‐ by 24 hours

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

0.85 [0.61, 1.19]

5.2 refusing oral drugs ‐ at 24 hours

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

0.69 [0.33, 1.44]

6 Adverse effects: Serious adverse effect Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

6.1 by 30 minutes

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.06, 15.95]

6.2 by 1 hour

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

6.3 by 2 hours

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

7 Service outcomes: Not discharged Show forest plot

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.84, 1.29]

7.1 by 15 days

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.84, 1.29]

8 Specific Behaviours: 1. Aggression. a ‐ other episode of aggression ‐ by 24 hrs Show forest plot

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

0.89 [0.62, 1.29]

9 Leaving the study early Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

9.1 by 2 hours

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

2.01 [0.18, 21.97]

9.2 by 24 hours

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.36, 2.80]

9.3 by 2 weeks

1

301

Risk Ratio (M‐H, Fixed, 95% CI)

0.14 [0.01, 2.76]

Figures and Tables -
Comparison 6. HALOPERIDOL + PROMETHAZINE vs BENZODIAZEPINES ‐ MIDAZOLAM
Comparison 7. HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL ‐ additional 40 minutes data

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Tranquil or asleep: 1. Not tranquil or asleep Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

1.1 by 40 minutes

1

316

Risk Ratio (M‐H, Fixed, 95% CI)

0.83 [0.56, 1.24]

2 Tranquil or asleep: 2. Not asleep Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

2.1 by 40 minutes

1

316

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.85, 1.16]

Figures and Tables -
Comparison 7. HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL ‐ additional 40 minutes data