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Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet]. York (UK): Centre for Reviews and Dissemination (UK); 1995-.

Database of Abstracts of Reviews of Effects (DARE): Quality-assessed Reviews [Internet].

Pharmacological management of agitation in emergency settings

A Yildiz, GS Sachs, and A Turgay.

Review published: 2003.

CRD summary

This review investigated drug treatments for acute agitation. The authors concluded that atypical antipsychotics used alone or in combination with a benzodiazepine should be considered first, and the combination of a conventional antipsychotic plus benzodiazepine second. However, the authors' conclusions do not follow directly from the somewhat equivocal results of the primary studies.

Authors' objectives

To review the effectiveness of conventional antipsychotics and/or benzodiazepines, and atypical antipsychotics in the treatment of acute agitation in the emergency setting.

Searching

MEDLINE was searched and the reference lists of retrieved articles and/or reviews were checked.

Study selection

Study designs of evaluations included in the review

No inclusion criteria for the study design were specified in the review. However, the authors appear to have intended to include only trials, although whether they were to be randomised or not was unclear. Study design was not listed as one of the characteristics of the included studies.

Specific interventions included in the review

Studies in which the patients were assigned to treatment with a conventional antipsychotic (classic high potency neuroleptic available in the USA), a benzodiazepine, or a combination of both, with one of the other two options as a comparator, were eligible for the review. With the exception of one study of droperidol, the included studies used haloperidol as the conventional antipsychotic; the benzodiazepines were lorazepam, alprozolam, flunitrazepam, clonazepam and midazolam.

Studies in which patients were assigned to either a novel antipsychotic, a conventional antipsychotic, a benzodiazepine or a placebo were also eligible. The novel antipsychotics in the included studies were risperidone, ziprasidone or olanzapine; the conventional antipsychotic was haloperidol; the benzodiazepine was lorazepam.

Participants included in the review

Studies of adult psychiatric patients with acute agitation were eligible for the review. Further details of those included in the review were not given.

Outcomes assessed in the review

For studies involving conventional antipsychotics, the outcomes had to be assessed within 4 hours of drug administration. For studies of atypical antipsychotics, the outcomes had to be assessed within 72 hours of drug administration. Specific criteria for the outcomes were not stated. A range of assessment scales were employed in the included trials: Brief Psychiatric Rating Scale, with various subscales; visual analogue scale for agitation; Overt Aggression Scale; sedation scale score; and Positive and Negative Syndrome Scale (PANSS). Note, the PANSS was only used in trials involving the atypical antipsychotics.

Adverse events, in particular extrapyramidal symptoms (EPS), were reported.

How were decisions on the relevance of primary studies made?

The authors did not state how the papers were selected for the review, or how many reviewers performed the selection.

Assessment of study quality

The authors did not state that they assessed validity.

Data extraction

The authors did not state how the data were extracted for the review, or how many reviewers performed the data extraction. Data were extracted on improvement rates, definition of improvement, and timing of the defined improvement for individual studies. The reviewers calculated the improvement rates for the individual trials based on data provided in the primary trials, unless they were originally given as percentages.

Methods of synthesis

How were the studies combined?

The two review questions were summarised separately: i.e. the trials for the evaluation of a conventional antipsychotic compared with a benzodiazepine or a combination of both were summarised separately from the trials for the evaluation of a novel antipsychotic versus a conventional antipsychotic, a benzodiazepine, or a placebo. The results from the primary studies were listed in tables, and described and discussed in the text.

How were differences between studies investigated?

A lack of homogeneity in terms of study design, patient selection, rating scales, definition of improvement and duration of treatment was identified.

Results of the review

There were 11 trials (n=701) for the evaluation of a conventional antipsychotic compared with a benzodiazepine or a combination of both.

There were 5 trials (n=711) for the evaluation of a novel antipsychotic versus a conventional antipsychotic or a benzodiazepine or a placebo. percentages.

All of the studies were referred to as trials, 11 of which were blinded.

Combination therapy versus conventional antipsychotic or benzodiazepine alone (4 studies): all 4 studies found that combination therapy was superior to either type of drug alone. Three of the studies reported fewer EPS with the combination than with a conventional antipsychotic alone.

Conventional antipsychotic versus benzodiazepine (7 studies): 2 studies (both of droperidol) reported significantly higher rates of improvement with conventional antipsychotics, three found no significant difference, and two found benzodiazepines provided significantly higher rates of improvement. Six studies reported fewer EPS with the benzodiazepine.

Atypical antipsychotics versus placebo (3 trials): 2 trials found greater efficacy with atypical antipsychotics.

Atypical antipsychotics versus conventional antipsychotic (3 trials): 1 trial found the atypical antipsychotic to be more effective, while the other 2 trials found no difference.

Atypical antipsychotics versus benzodiazepine (1 trial): the trial found the atypical antipsychotic to be more effective.

Atypical antipsychotics plus benzodiazepine versus conventional antipsychotic plus benzodiazepine (2 trials): there was no significant difference between the treatments.

All 5 trials reported side-effects and found the incidence of EPS to be lower with atypical antipsychotics than with conventional antipsychotics.

Authors' conclusions

Atypical antipsychotics used alone or in combination with a benzodiazepine should be considered first in the treatment of acute agitation. If these agents are not available, the combination of a conventional antipsychotic plus benzodiazepine is acceptable. Oral administration of drugs is the preferred route.

CRD commentary

This review addressed two closely related questions regarding the best drug treatment for acute agitation. Apart from the drug comparisons to be included within the studies, the criteria for inclusion in the review were poorly defined. The literature search was very limited, comprising of a search of only one electronic database and some reference checking. The details of the review methodology were also poorly reported, making it difficult to assess the level of potential reviewer bias. Details of the primary studies were tabulated but important details, such as study design and how this might affect the findings, were not discussed. In addition, study quality was not assessed.

The narrative synthesis seemed appropriate given the diversity of the studies. However, the synthesis was not presented clearly and the reader has to resort to the individual study tables. The authors' conclusions do not follow directly from the somewhat equivocal primary study results and should be interpreted with caution.

Implications of the review for practice and research

Practice: The authors stated that atypical antipsychotics such as risperidone, ziprasidone and olanzapine, with or without benzodiazepines, should be considered first in the treatment of acute agitation. If these agents are not available, the combination of a classic antipsychotic and a benzodiazepine would be a reasonable alternative.

Research: The authors did not state any implications for further research.

Bibliographic details

Yildiz A, Sachs G S, Turgay A. Pharmacological management of agitation in emergency settings. Emergency Medicine Journal 2003; 20(4): 339-346. [PMC free article: PMC1726160] [PubMed: 12835344]

Indexing Status

Subject indexing assigned by NLM

MeSH

Adolescent; Adult; Aggression /drug effects; Antipsychotic Agents /therapeutic use; Benzodiazepines /therapeutic use; Clinical Trials as Topic; Drug Therapy, Combination; Emergencies; Emergency Services, Psychiatric /methods; Female; Humans; Male; Middle Aged; Psychomotor Agitation /drug therapy; Psychotic Disorders /drug therapy

AccessionNumber

12003001469

Database entry date

30/11/2006

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.

CRD has determined that this article meets the DARE scientific quality criteria for a systematic review.

Copyright © 2014 University of York.

PMID: 12835344