Haloperidol más prometazina para la agresión inducida por psicosis
Información
- DOI:
- https://doi.org/10.1002/14651858.CD005146.pub3Copiar DOI
- Base de datos:
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- Cochrane Database of Systematic Reviews
- Versión publicada:
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- 25 noviembre 2016see what's new
- Tipo:
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- Intervention
- Etapa:
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- Review
- Grupo Editorial Cochrane:
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Grupo Cochrane de Esquizofrenia
- Copyright:
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- Copyright © 2016 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Cifras del artículo
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Autores
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
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Universidade Federal de Rio de Janeiro, Brazil.
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Christian Medical Centre, Vellore, India.
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University of Colorado School of Medicine, USA.
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National Institute of Quality Control in Health, Oswald Cruz Foundation, Brazil.
External sources
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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 | |
| 2009 Jul 08 | Haloperidol plus promethazine for psychosis‐induced aggression | Review | Gisele Huf, Jacob Alexander, Michael H Allen, Nirmal S Raveendran | |
| 2004 Oct 18 | Haloperidol plus promethazine for psychosis‐induced aggression | Review | Gisele Huf, Jacob Alexander, Michael H Allen, Nirmal S Raveendran | |
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
Medical Subject Headings (MeSH) Keywords
- Aggression [*drug effects, psychology];
- Benzodiazepines [therapeutic use];
- Drug Therapy, Combination;
- Haloperidol [*therapeutic use];
- Lorazepam [therapeutic use];
- Midazolam [therapeutic use];
- Promethazine [*therapeutic use];
- Psychomotor Agitation;
- Psychotic Disorders [*drug therapy, psychology];
- Randomized Controlled Trials as Topic;
- Restraint, Physical [statistics & numerical data];
Medical Subject Headings Check Words
Humans;
PICO
Haloperidol structure.
Promethazine structure.
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.
Study flow diagram 2015 update.
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.
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.
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 |
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.
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.
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.
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).
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.
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.
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).
| 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 | ||
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 |
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 |
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.
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.
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 |
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.
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.
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.
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).
Comparison 2 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ OLANZAPINE, Outcome 20 Service outcomes.
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).
| 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 |
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 |
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.
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 |
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.
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.
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).
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.
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 |
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 |
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.
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 |
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.
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.
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).
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.
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.
| 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 | ||
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.
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.
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) ).
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.
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.
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.
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.
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.
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.
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.
Comparison 7 HALOPERIDOL + PROMETHAZINE vs ANTIPSYCHOTIC ‐ HALOPERIDOL ‐ additional 40 minutes data, Outcome 2 Tranquil or asleep: 2. Not asleep.
| 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 | |||
| + none specified | Not applicable | Haloperidol | Haloperidol + midazolam | |||
| Olanzapine | ||||||
| Ziprasidone | ||||||
| Risperidone + lorazepam | ||||||
| Haloperidol + midazolam | Olanzapine | |||||
| Ziprasidone | ||||||
| Haloperidol + promethazine | Lorazepam | |||||
| Olanzapine | Ziprasidone | |||||
| Chlorpromazine | Phenobarbital | Not applicable | ‐ | |||
| Placebo | ||||||
| Promethazine | ‐ | |||||
| Perazine | Trimipramine | ‐ | ||||
| Phenobarbital | Placebo | ‐ | ||||
| Promethazine | Phenobarbital | ‐ | ||||
| Placebo | ‐ | |||||
| Risperidone (2 mg) | Risperidone (4 mg) | |||||
| Trifluoperazine | Placebo | |||||
| + “mental deficiency" [? learning disability] | Chlorpromazine | Periciazine | ‐ | |||
| + drug‐induced parkinsonism/EPS | Mazaticol hydrochloride | Promethazine | ‐ | |||
| Trihexyphenidyl | ‐ | |||||
| Methixene | Promethazine | ‐ | ||||
| Trihexyphenidyl | ‐ | |||||
| Piroheptine | Promethazine | ‐ | ||||
| Trihexyphenidyl | ‐ | |||||
| Procyclidine | Promethazine | |||||
| Promethazine | Placebo | ‐ | ||||
| + drug‐induced parkinsonism/EPS | Promethazine | Trihexyphenidyl | ‐ | |||
| + tardive dyskinesia | Pimozide | Placebo | ||||
| Promethazine | ‐ | |||||
| EPS: extrapyramidal symptoms | ||||||
| Methods | Allocation: randomised (clearly described). |
| Participants | Diagnosis: anyone whose aggressive behaviour is thought to be due to psychotic illness. N=300. |
| 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 |
| HALOPERIDOL + PROMETHAZINE compared to ANTIPSYCHOTIC ‐ HALOPERIDOL for psychosis‐induced aggression | ||||||
| Patient or population: people with psychosis‐induced aggression | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| ANTIPSYCHOTIC ‐ HALOPERIDOL | HALOPERIDOL + PROMETHAZINE | |||||
| Tranquil or asleep: Not tranquil or asleep ‐ by 30 minutes | Moderate1 | RR 0.65 | 316 | ⊕⊕⊕⊕ | ||
| 500 per 1000 | 325 per 1000 | |||||
| Global state: | Moderate1 | RR 0.83 | 60 | ⊕⊕⊝⊝ | ||
| 200 per 1000 | 166 per 1000 | |||||
| Adverse effects: Specific and serious adverse effects by 24 hours (not death) | Moderate1 | RR 0.95 | 298 | ⊕⊕⊝⊝ | ||
| 10 per 1000 | 9 per 1000 | |||||
| Adverse effect: Specific and serious ‐ Death | See comment | See comment | Not estimable | 0 | See comment | No study reported this outcome |
| Service outcomes: Not discharged ‐ by 2 weeks | Moderate1 | RR 0.83 | 310 | ⊕⊕⊕⊕ | ||
| 500 per 1000 | 415 per 1000 | |||||
| Specific behaviours: Average aggression score ‐ by 12 hours | The mean specific behaviours: average aggression score in the intervention groups was | 60 | ⊕⊕⊝⊝ | |||
| Economics: Costs of care | See comment | See comment | Not estimable | 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). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Moderate control risk approximates to that of the included trial(s). | ||||||
| HALOPERIDOL + PROMETHAZINE compared to ANTIPSYCHOTIC ‐ OLANZAPINE for psychosis‐induced aggression | ||||||
| Patient or population: people with psychosis‐induced aggression | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| ANTIPSYCHOTIC ‐ OLANZAPINE | HALOPERIDOL + PROMETHAZINE | |||||
| Tranquil or asleep: Not tranquil or asleep ‐ by 30 mins | Moderate1 | RR 0.60 | 300 | ⊕⊕⊕⊕ | ||
| 100 per 1000 | 60 per 1000 | |||||
| Global state: | Moderate | RR 5.00 | 60 | ⊕⊕⊝⊝ | ||
| 50 per 10001 | 250 per 1000 | |||||
| Adverse effects: Specific and serious adverse effects by 24 hours | Moderate | RR 0.67 | 116 | ⊕⊕⊝⊝ | ||
| 100 per 10001 | 64 per 1000 | |||||
| Adverse effect: Specific ‐ Death | See comment | See comment | Not estimable | 0 | See comment | No study reported this outcome |
| Service outcomes: Not discharged ‐ by 4 hours | Moderate | RR 0.94 | 300 | ⊕⊕⊕⊕ | ||
| 600 per 10001 | 564 per 1000 | |||||
| Specific behaviours: Average aggression score ‐ by 12 hours | The mean specific behaviours: average aggression score in the intervention groups was | 60 | ⊕⊕⊝⊝ | |||
| Economics: Costs of care7 | See comment | See comment | Not estimable | 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). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Moderate control risk approximates to that of the included trial(s). | ||||||
| HALOPERIDOL + PROMETHAZINE compared to ANTIPSYCHOTIC ‐ ZIPRASIDONE for psychosis‐induced aggression | ||||||
| Patient or population: people with psychosis‐induced aggression | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| ANTIPSYCHOTIC ‐ ZIPRASIDONE | HALOPERIDOL + PROMETHAZINE | |||||
| Tranquil or asleep: Average sedation score ‐ by 30 minutes | The mean tranquil or asleep: average sedation score in the intervention groups was | 60 | ⊕⊕⊝⊝ | |||
| Global state: Needing restraints or seclusion ‐ by 12 hours | Moderate | RR 0.5 | 60 | ⊕⊕⊕⊝ | ||
| 400 per 10003 | 200 per 1000 | |||||
| Adverse effects: Specific and serious adverse effect ‐ by 24 hours | Moderate | RR 0.30 | 111 | ⊕⊕⊝⊝ | ||
| 150 per 10003 | 47 per 1000 | |||||
| Adverse effect: Specific ‐ Death | See comment | See comment | Not estimable | 0 | See comment | No study reported this outcome |
| Service outcomes: Not discharged ‐ by 2 weeks | See comment | See comment | Not estimable | 0 | See comment | No study reported this outcome |
| Specific behaviours: Average aggression score ‐ by 12 hours | The mean specific behaviours: average aggression score in the intervention groups was | 60 | ⊕⊕⊕⊝ | |||
| Economics: Costs of care | See comment | See comment | Not estimable | 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). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Indirectness: rated 'serious' ‐ pre‐stated outcome 'Tranquil or asleep' ‐ proxy outcome used. | ||||||
| HALOPERIDOL + PROMETHAZINE compared to ANTIPSYCHOTIC & BENZODIAZEPINE ‐ HALOPERIDOL + MIDAZOLAM for psychosis‐induced aggression | ||||||
| Patient or population: people with psychosis‐induced aggression | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| ANTIPSYCHOTIC & BENZODIAZEPINE ‐ HALOPERIDOL + MIDAZOLAM | HALOPERIDOL + PROMETHAZINE | |||||
| Tranquil or asleep: Average sedation score ‐ by 1 hour | The mean tranquil or asleep: average sedation score in the intervention groups was | 60 | ⊕⊕⊝⊝ | |||
| Global state: Needing restraints or seclusion ‐ by 12 hours | Moderate | RR 0.24 | 60 | See comment | ||
| 700 per 10002 | 168 per 1000 | |||||
| Adverse effects: Specific and serious adverse effect ‐ by 24 hours | Moderate | RR 0.12 | 117 | ⊕⊕⊝⊝ | ||
| 300 per 10002 | 33 per 1000 | |||||
| Adverse effect: Specific ‐ Death | See comment | See comment | Not estimable | 0 | See comment | No study reported this outcome |
| Service outcomes: Not discharged ‐ by 2 weeks | See comment | See comment | Not estimable | 0 | See comment | No study reported this outcome |
| Specific behaviours: Average aggression score ‐ by 12 hours | The mean specific behaviours: average aggression score in the intervention groups was | 60 | See comment | |||
| Economics: Costs of care | See comment | See comment | Not estimable | 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). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Indirectness: rated 'serious' ‐ pre‐stated outcome 'tranquil or asleep' ‐ proxy outcome used. | ||||||
| HALOPERIDOL + PROMETHAZINE compared to BENZODIAZEPINES ‐ LORAZEPAM for psychosis‐induced aggression | ||||||
| Patient or population: people with psychosis‐induced aggression | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| BENZODIAZEPINES ‐ LORAZEPAM | HALOPERIDOL + PROMETHAZINE | |||||
| Tranquil or asleep: Not tranquil or asleep ‐ by 30 mins | Moderate | RR 0.26 | 200 | ⊕⊕⊕⊕ | ||
| 200 per 10001 | 52 per 1000 | |||||
| Global state: Needing restraints or seclusion ‐ by 12 hours | Moderate | RR 0.82 | 200 | ⊕⊕⊕⊝ | ||
| 150 per 10001 | 123 per 1000 | |||||
| Adverse effects: Specific and serious adverse effect ‐ by 24 hours | See comment | Not estimable | 0 | See comment | No study reported for this outcome | |
| Adverse effect: Specific ‐ Death | See comment | Not estimable | 0 | See comment | No study reported for this outcome | |
| Service outcomes: Not discharged ‐ by 4 hours | Moderate | RR 1.13 | 200 | ⊕⊕⊕⊕ | ||
| 500 per 10001 | 565 per 1000 | |||||
| Specific behaviours: Average aggression score | See comment | See comment | Not estimable | 0 | See comment | No study reported for this outcome |
| Economics: Costs of care | See comment | See comment | Not estimable | 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). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Moderate control risk approximates to that of the included trial. | ||||||
| HALOPERIDOL + PROMETHAZINE compared to BENZODIAZEPINES ‐ MIDAZOLAM for psychosis‐induced aggression | ||||||
| Patient or population: people with psychosis‐induced aggression | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No of Participants | Quality of the evidence | Comments | |
| Assumed risk | Corresponding risk | |||||
| BENZODIAZEPINES ‐ MIDAZOLAM | HALOPERIDOL + PROMETHAZINE | |||||
| Tranquil or asleep: Not tranquil or asleep | Moderate | RR 2.9 | 301 | ⊕⊕⊕⊕ | ||
| 200 per 10001 | 580 per 1000 | |||||
| Global state: Needing restraints or seclusion‐ by 2 hours | Moderate | RR 1.22 | 301 | ⊕⊕⊕⊝ | ||
| 250 per 10001 | 305 per 1000 | |||||
| Adverse effect: Specific ‐ Death | See comment | See comment | Not estimable | 0 | See comment | No study reported for this outcome |
| Service outcomes: Not discharged ‐ | Moderate | RR 1.05 | 301 | ⊕⊕⊕⊕ | ||
| 550 per 10001 | 577 per 1000 | |||||
| Specific behavioursAggression | Moderate | RR 0.89 | 301 | ⊕⊕⊕⊝ | ||
| Economics: Costs of care | See comment | See comment | Not estimable | 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). | ||||||
| GRADE Working Group grades of evidence | ||||||
| 1Moderate control risk approximates to that of the included trial. | ||||||
| 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 |
| Focus of review | Reference |
| Completed and maintained reviews | |
| 'As required' medication regimens for seriously mentally ill people in hospital | |
| Benzodiazepines for psychosis‐induced aggression or agitation | |
| Chlorpromazine for psychosis‐induced aggression or agitation | |
| Clotiapine for acute psychotic illnesses | |
| Containment strategies for people with serious mental illness | |
| Droperidol for acute psychosis | |
| Haloperidol for psychosis‐induced aggression or agitation (rapid tranquillisation) | |
| Olanzapine IM or velotab for acutely disturbed/agitated people with suspected serious mental illnesses | |
| Seclusion and restraint for serious mental illnesses | |
| Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses | |
| Reviews in the process of being completed | |
| Risperidone for psychosis‐induced aggression or agitation | |
| Haloperidol for long‐term aggression in psychosis | |
| Loxapine inhaler for psychosis‐induced aggression | |
| Clozapine for people with schizophrenia and recurrent physical aggression | |
| Quetiapine for psychosis‐induced aggression or agitation | |
| De‐escalation techniques for psychosis‐induced aggression | |
| 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] |
| 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] |
| 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] |
| 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] |
| 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] |
| 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] |
| 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] |
