Objective: Evidence base for rapid tranquillisation is an under researched area. Guidelines on rapid tranquilisation from English speaking countries were appraised using AGREE (Appraisal of Guidelines Research and Evaluation) and differences in their recommendations were analysed. Methods: Four independent psychiatrists appraised the guidelines using the AGREE tool. AGREE is a validated instrument used to assess the quality of guideline and recommendations using six domains of which each domain captures a specific aspect of the guideline development. The content was analysed manually. Results: Seven guidelines from five English speaking countries met the inclusion criteria. All the guidelines scored well on the domain of “scope and purpose”. NICE guidelines from the UK consistently scored well on all domains with the maximum possible score of 100 on the “applicability” domain. APA from the USA did well on the domain of “editorial independence”. AGREE could only examine the guideline development process and not the content. The guidelines differed in their recommendations of choice of drug for rapid tranquillisation. Discussion: All guidelines scored reasonably well on AGREE. National Institute of Clinical Excellence (NICE) has used robust strategies in developing the guidelines. Guidelines failed to achieve consensus in recommendations despite using a common pool of evidence. Haloperidol-promethazine combination is not recommended by any with the exception of NICE. This suggests data is selectively interpreted depending on locally prevalent customs.
Violent or aggressive behaviour is a psychiatric emergency that necessitates swift mobilisation of staff and resources. Commonly it is secondary to psychotic symptoms, physical illness (e.g. delirium) and substance abuse [
Rapid tranquillisation is the use of medication to manage agitated or aggressive behaviour [
. Surveys on rapid tranquillisation
Year | Authors | Methods | Participants | Location | Response | Duration | Results |
---|---|---|---|---|---|---|---|
1992 | Pilowsky et al. | Retrospective practice-based | Doctors and nurses | South London, UK | 95% | 6 months | Mean doses of parenteral antipsychotics and sedatives exceeded BNF* recommendations. |
1994 | Cunnane et al. | Retrospective vignette-based | General adult consultants | Oxford, UK | 68% | Not mentioned | No clear consensus. Chlorpromazine preferred over haloperidol. IM route favoured. |
1996 | Simpson et al. | Retrospective vignette-based | Consultants and registrars | Manchester, UK | 67% | Not mentioned | Haloperidol preferred to chlorpromazine. BNF maximum doses felt to be inadequate to control severe aggression. |
1997 | Mannion et al. | Retrospective practice-based | Psychiatry trainees | Dublin, Ireland | 80% | 6 months | High dose antipsychotics and IM routes preferred. Zuclopenthixol acetate used in nearly half the incidents. |
1998 | Hyde et al. | Retrospective practice-based | Nurse-based computerised database | Manchester, UK | 100% | 24 months | Zuclopenthixol or haloperidol + lorazepam IM preferred. Higher doses used in disturbed or resistant cases. |
1999 | Binder et al. | Retrospective practice-based | Medical directors of emergency settings | USA-wide | 100% | 1 month | Haloperidol-lorazepam combination favoured. IM route preferred. |
1999 | Moritz et al. | Prospective practice-based | 100 consecutive patients in emergency room | Rouen, France | 100% | 9 months | Intramuscular loxapine was the preferred drug of choice. |
2002 | Huf et al. | Retrospective practice-based | Practitioners in psychiatric emergency room | Rio de Janeiro, Brazil | 100% | 1 week | Haloperidol-promethazine combination preferred by 83% of participants. |
2003 | Reid et al. | Retrospective practice-based | Consultants | West Scotland, UK | 84% | Not mentioned | Droperidol perceived to be more effective than haloperidol or chlorpromazine Disapproval at its withdrawal. |
2005 | Pereira et al. | Retrospective practice-based | Consultants and trainees | UK-wide | 22% | Not mentioned | Lorazepam and haloperidol favoured with most doses exceeding BNF limits. Chlorpromazine, zuclopenthixol and droperidol next in line. |
: Surveys of clinicians’ preferred choices; *BNF: British National Formulary.
The Appraisal of Guidelines Research and Evaluation (AGREE) is an instrument used to assess the methodological rigour and potential biases involved in guideline development. It also checks for the internal and external validity of the recommendations [
Four independent raters rate the guidelines on these domains using a four point scale. The scores on the six domains are independent and cannot be aggregated. These scores help to compare the different guidelines and to decide whether or not to recommend a particular guideline over others. However it is not possible to set thresholds for the domain scores to demarcate a good guideline from a bad one.
Guidelines on rapid tranquillisation from all English speaking countries were appraised using AGREE, with special emphasis on the NICE guidelines [
Major databases were searched through the electronic database OVID. The databases included EMBASE (1980 to October week 3 2008), CINAHL (1982 to October week 3 2008), MEDLINE (1950 to October week 3 2008) and PsycINFO (1806 to October week 3 2008).The search terms used were “rapid tranquillisation” “tranquillisation” “behavioural emergencies”, “aggression”, “psychiatry emergencies”, ”guidelines in psychiatry” and “expert consensus guidelines”. After dropping the duplicates and hand searching the abstracts seven guidelines in English language were obtained from five countries: UK, USA, Canada, Australia and New Zealand which met our inclusion criteria. The eighth guideline from Singapore was excluded as it did not meet the criterion of an English-speaking country.
Four raters used the AGREE tool to objectively assess potential biases of guidelines. The assessors were trainee psychiatrists at different levels of their training. Two of them were senior house officers: one in his first year of training and the second in his second year of training. A specialist registrar (one of the authors) and a staff grade psychiatrist both in their fourth year of training formed the team of assessors. The raters had received prior instructions regarding the scoring process. The guidelines were scored on six domains mentioned above. The scores were then standardised according to validated recommendations which could range from 0 to 100%. The content of the guidelines was analysed separately as it was not rated by the AGREE tool.
Seven guidelines identified as above were compared for their pharmacological recommendations (
Their methodological quality was evaluated using AGREE (
. Guideline recommendations for rapid tranquillisation
Date | Source | Guideline | Drugs recommended | Route of admin | Comments | |
---|---|---|---|---|---|---|
2004 | USA | American Psychiatric Association (APA) | Dissolvable olanzapine/risperidone OR Concentrate formulation of risperidone/haloperidol | PO | Droperidol: in selected clinical situations of extreme emergency or in highly agitated patients. | |
Haloperidol/ziprasidone/ olanzapine +/− lorazepam | IM | |||||
2005 | Canada | Canadian Psychiatric Association (CPA) | Dissolvable SGAs | PO | Zuclopenthixol acetate: recommended to avoid repeated injections, except in drug naïve patients. | |
Haloperidol 5 mg + lorazepam 2 mg OR olanzapine (2.5 - 10 mg) | IM | |||||
2005 | USA | Expert Consensus Guidelines (ECG) | Personality disorder/ Intoxication/ No data | Benzodiazepines | PO | Medication and patient characteristics govern the choice of psychotropic used |
Schizophrenia/ Mania | Olanzapine/risperidone +/−BNZ/ haloperidol + BNZ/valproex + antipsychotic | PO | ||||
Ziprasidone/quetiapine | PO | |||||
Olanzapine/ziprasidone +/− BNZ/haloperidol + BNZ | IM | |||||
2005 | UK | National Institute for Clinical Excellence Guidelines (NICE) | Haloperidol/lorazepam/ olanzapine/risperidone | PO | Olanzapine/risperidone: avoid in dementia. IV benzodiazepine/haloperidol: exceptional cases Oral or IM lorazepam alone: non-psychotic behavioural disturbance IM (haloperiodol + promethazine) /IM midazolam: very exceptional cases. Zuclopenthixol acetate: recommended in few, other than drug naïve patients. Chlorpromazine: not recommended at all. | |
Haloperidol + lorazepam OR Olanzapine | IM | |||||
2003 | USA | Patient Outcomes Research Team (PORT) | Antipsychotic + benzodiazepine | Not specified | No details explained. | |
2004 | Australia & New Zealand | Royal Australian & New Zealand College of Psychiatrists (RANZP) | Lorazepam (1 - 2 mg)/diazepam (5 - 10 mg) | PO | Typical antipsychotics: recommended as a last resort owing to risk of EPS. Haloperidol: least effective strategy. Alternative options: chlorpromazine (50 - 100 mg PO)/clonazepam (0.5 - 2 mg IM)/olanzapine(IM). Droperidol (IM): in nonresponsive cases. Zuclopenthixol acetate: recommended to avoid frequent injections even in drug naïve patients. IV midazolam may be used for rapid onset of action. | |
Olanzapine wafers (5 - 10 mg)/ quetiapine (50 - 100 mg) | PO | |||||
Midazolam 5 mg | IM | |||||
2003 | USA | Texas Implementation of Medication Algorithms (TIMA) | Benzodiazepine/FGA | PO/IM | Benzodiazepines (lorazepam 1 - 8 mg/day, clonazepam 0.5 - 2 mg/day) & FGAs: preferred over SGAs irrespective of route. SGAs seem less effective for agitation/ excitement of an acute exacerbation. | |
Risperidone solution | PO | |||||
Olanzapine/ziprasidone | IM |
FGA = first generation antipsychotic; SGA = second generation antipsychotic; BNZ = benzodiazepine. Colour code: Yellow = 1st choice, Green = 2nd choice, Red = 3rd choice.
Common themes in clinical practice can be identified. For instance, benzodiazepines are chosen when little background information about the patient is available. This is in keeping with the Expert Consensus Guidelines [
. Methodological quality of guidelines
Guideline | Standardised AGREE Scores for each Domain (Percentage of maximum available score) | |||||
---|---|---|---|---|---|---|
Domain 1 Scope & Purpose | Domain 2 Stakeholder involvement | Domain 3 Rigour of development | Domain 4 Clarity & presentation | Domain 5 Applicability | Domain 6 Editorial independence | |
APA | 94 | 63 | 90 | 83 | 33 | 100 |
CPA | 94 | 54 | 93 | 75 | 50 | 96 |
ECG | 94 | 73 | 65 | 83 | 61 | 79 |
NICE | 97 | 79 | 74 | 96 | 100 | 63 |
PORT | 78 | 44 | 85 | 50 | 42 | 58 |
RANZP | 89 | 73 | 79 | 67 | 47 | 83 |
TIMA | 92 | 54 | 71 | 71 | 67 | 46 |
lack of good quality evidence necessitates those drawing up guidance to draw conclusions that are not founded on best possible evidence. For instance the only existing trial of zuclopenthixol acetate has a sample size of 40 patients [
Consensus on rapid tranquillisation guidelines is the need of the hour. Whether better quality clinical trials can help us reach an AGREEment remains to be seen.
None.