Skip to main content
×
×
Home

Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting: Pragmatic randomised trial of intramuscular lorazepam v. haloperidol plus promethazine

  • Jacob Alexander (a1), Prathap Tharyan (a1), Clive Adams (a2), Thomas John (a1), Carina Mol (a3) and Joncy Philip (a1)...
Abstract
Background

The pharmacological management of violence in people with psychiatric disorders is under-researched.

Aims

To compare interventions commonly used for controlling agitation or violence in people with serious psychiatric disorders.

Method

We randomised 200 people to receive intramuscular lorazepam (4 mg) or intramuscular haloperidol (10 mg) plus promethazine (25–50 mg mix).

Results

At blinded assessments 4 h later (99.5% follow-up), equal numbers in both groups (96%) were tranquil or asleep. However, 76% given the haloperidol-promethazine mix were asleep compared with 45% of those allocated lorazepam (RR=2.29, 95% CI 1.59–3.39; NNT=3.2, 95% CI 2.3–5.4). The haloperidol-promethazine mix produced a faster onset of tranquillisation/sedation and more clinical improvement over the first 2 h. Neither intervention differed significantly in the need for additional intervention or physical restraints, numbers absconding, or adverse effects.

Conclusions

Both interventions are effective for controlling violent/agitated behaviour. If speed of sedation is required, the haloperidol-promethazine combination has advantages over lorazepam.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting
      Available formats
      ×
Copyright
Corresponding author
Dr Jacob Alexander, Department of Psychiatry, Christian Medical College, Vellore 632002, Tamil Nadu, India. Tel: 91 416 2262603, ext. 4259; fax: 91 416 2261632; e-mail: dralexander=in@yahoo.com
Footnotes
Hide All

Declaration of interest

None.

Footnotes
References
Hide All
Allen, M. H. (2002) Managing the agitated psychotic patient: a reappraisal of the evidence. journal of Clinical Psychiatry, 61 (suppl. 14), 1120.
Altman, D. G. (1998) Confidence intervals for the number needed to treat. BMJ, 317, 13091312.
Barnes, T. R. E. (1989) A rating scale for drug-induced akathisia. British journal of Psychiatry, 154, 672676.
Battaglia, J., Moss, S., Rush, J., et al (1997) Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study. American journal of Emergency Medicine, 15, 335340.
Binder, R. L. & McNeil, D. E. (1999) Emergency psychiatry: contemporary practices in managing acutely violent patients in 20 psychiatric emergency rooms. Psychiatric Services, 50, 15531554.
Brook, S., Lucey, J. V. & Gunn, K. P., et al (2000) Intramuscular ziprasidone compared with intramuscular haloperidol in the treatment of acute psychosis. Journal of Clinical Psychiatry, 61, 933941.
Coutinho, E., Fenton, M., Adams, C., et al (2000) Zuclopenthixol acetate in psychiatric emergencies: looking for evidence from clinical trials. Schizophrenia Research, 46, 111118.
Cunnane, J. G. (1994) Drug management of disturbed behaviour by psychiatrists. Psychiatric Bulletin, 18, 138139.
Expert Consensus Guideline Group (1999) Treatment of schizophrenia 1999. The expert consensus guideline series. Journal of Clinical Psychiatry, 60 (suppl. 11), 380.
Fenton, M., Coutinho, E. S. F. & Campbell, C. (2003) Zuclopenthixol acetate in the treatment of acute schizophrenia and similar serious mental illnesses. Cochrane Library issue I. Oxford: Update Software.
Guy, W. (1976) ECDEU Assessment Manual for Psychopharmacology revised edn. Rockville, MD: National Institute of Mental Health.
Huf, G., Coutinho, E. S. F., Fagundes, H. M. Jr, et al (2002a) Current practices in managing acutely disturbed patients at three hospitals in Rio de Janeiro-Brazil: a prevalence study BMC Psychiatry, 2, 4.
Huf, G., Coutinho, E. S. F. & Adams, C. E. (2002b) TREC-Rio trial: a randomised controlled trial for rapid tranquillisation for agitated patients in emergency psychiatric rooms [ISRCTN44153243]. BMC Psychiatry, 2, II.
Jones, B., Taylor, C. C. & Meehan, K. (2001) The efficacy of a rapid-acting intramuscular formulation of olanzepine for positive symptoms. Journal of Clinical Psychiatry, 62 (suppl. 2), 2224.
Joy, C. B., Adams, C. E. & Lawrie, S. M. (2003) Haloperidol versus placebo for schizophrenia. Cochrane Library, issue I. Oxford: Update Software.
McAllister-Williams, R. H. & Ferrier, I. N. (2002) Rapid tranquillisation: time for a reappraisal of options for parenteral therapy. British Journal of Psychiatry, 180, 485489.
Pilowsky, L. S., Ring, H., Shine, P. J., et al (1992) Rapid tranquillisation. A survey of emergency prescribing in a general psychiatric hospital. British Journal of Psychiatry, 160, 831835.
Reddy, M. V. & Chandrasekhar, C. R. (1998) Prevalence of mental and behavioural disorders in India: a metaanalysis. Indian Journal of Psychiatry, 40, 149157.
Royal College of Psychiatrists (1998) Management of Imminent Violence: Clinical Practice Guidelines to Support Mental Health Services (Occasional Paper OP41). London: Royal College of Psychiatrists.
Salzman, C., Solomon, D., Miyawaki, E., et al (1991) Parenteral lorazepam versus parenteral haloperidol for the control of psychotic disruptive behavior. Journal of Clinical Psychiatry, 52, 177180.
Simpson, E. N. & Angus, J. W. F. (1970) Arating scale for extrapyramidal side-effects. Acta Psychiatrica Scandinavica Supplementum, 212, 1119.
Tardif, K. & Sweillam, A. (1982) Assaultive behavior among chronic inpatients. American Journal of Psychiatry, 139, 212215.
Tardiff, K. & Koenigsberg, H. W. (1985) Assaultive behavior among psychiatric outpatients. American Journal of Psychiatry, 142, 960963.
TREC Collaborative Group (2003) Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine. BMJ, 327, 708713.
Van Harten, P. N., Hoel, H. W. & Kahn, R. S. (1999) Acute dystonia induced by drug treatment. BMJ, 319, 623626.
World Health Organization (1992) The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. Geneva: WHO.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

The British Journal of Psychiatry
  • ISSN: 0007-1250
  • EISSN: 1472-1465
  • URL: /core/journals/the-british-journal-of-psychiatry
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 30 *
Loading metrics...

Abstract views

Total abstract views: 281 *
Loading metrics...

* Views captured on Cambridge Core between 2nd January 2018 - 26th May 2018. This data will be updated every 24 hours.

Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting: Pragmatic randomised trial of intramuscular lorazepam v. haloperidol plus promethazine

  • Jacob Alexander (a1), Prathap Tharyan (a1), Clive Adams (a2), Thomas John (a1), Carina Mol (a3) and Joncy Philip (a1)...
Submit a response

eLetters

Rapid tranquillisation of violent patients

Om Prakash Jhirwal, Senior Resident
27 April 2005

To the editor,

In their excellent paper Alexander et al (2004) systematically conducted comparison trial of intramuscular lorazepam and haloperidol-promethazine in violent or agitated patients. The authors have utilized a prospective follow-up design, used proper diagnostic assessment measures, thus taking care of most of the methodological plans have plagued researchin this area.

However, a few concerns about the study persists. Ideally, there is aneed of a viable placebo arm in order to compare the efficacy of both interventions. A comparison of a new agent against a drug previously shownto be active without a placebo comparator is uninterpretable unless one agent is superior to the others. Concluding that a drug is efficacious without a placebo comparator can lead to an incorrect assumption of efficacy if neither the investigational drug nor the active drug was, in that trial, any better than placebo would have been if included. Introducing a drug into therapeutic use on the basis of such a trial wouldexpose patients to a compound with no greater benefit than placebo (Temple& Ellenberg, 2000). Placebo is also important in the assessment of safety profile, as it provides a base rate for determining which adverse events are truly related to the investigational drug. For these reasons, placebo-controlled trails are almost universally demanded by regulatory bodies to demonstrated efficacy for any pharmacological interventions.

The authors have not discussed about investigations to rule out toxicstates, epilepsy and other organic conditions. They have failed to commentover vital parameters during and after administration of both interventions. They could have assessed level of satisfaction of treatmentteam with intervention (Petrack et al.1996). They could also apply any scale on aggression, agitation, alertness and psychopathology (Battaglia et al.1997).

Certain issues, however, merit consideration before accepting the authors conclusion. The better outcomes of haloperidol – promethazine group over lorazepam could be possibly due to two reasons. Firstly, combination group had manic patients (i.e. more problematic) than lorazepam group (Table 1, p.65). Secondly, it is evident from the same table that combination group had more moderately ill and less severely illpatients as compared to lorazepam group having less moderately ill and more severely ill. In addition to this, the details of additional medications was not mentioned in the paper. It remains a possibility that some improvement were due to effects of additional medications in both groups.

The authors commented that twenty three patients failed to sleep at all during the 4 hour follow-up compared with only eight in the combination group (para 1, p.65) which is different to understand from Table 2 (p.66 ). There were some inconsistent findings in the paper like sleep outcomes in combination group at 120 minutes were 69% and 88% as reflected from Table 2 and Table 5(p.68) respectively. Similarly, there was discrepancy in number of patients in combination group who never tranquil while describing results and in Table 2.

Nevertheless, we feel that the authors have taken a useful step in this relatively neglected area. Further studies are required about effectiveness of these interventions in the hope that better understandingcan lead to better treatment of violent patients.

REFERENCES

1.Alexander, J., Tharyan, P., Adams, C., et al. (2004) Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting. British Journal of Psychiatry, 185, 63-69.2.Temple, R & Ellenberg, S. (2000) Placebo-controlled trials and active control trials in the evaluation of new treatment. Part I : ethicaland scientific issues. Annals of Internal Medicine, 133, 455-463.3.Petrack, E.M., Marx, C.M., Wright, M.S. (1996) Intramuscular ketamine is superior to meperidine, promethazine, and chlorpromazine for paediatricemergency department sedation. Archives of Paediatric and Adolescent medicine, 150 (7), 676-681.4.Battaglia, J., Moss, S., Rush, J., et al. (1997). Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study. American Journal of Emergency Medicine, 15(4), 335-340.
... More

Conflict of interest: None Declared

Write a reply

What is the evidence for it and how rigorously has it been obtained?

Muzaffar Husain, SHO in Old Age Psychiatry
03 September 2004

Research dies without debate, and this letter has been drafted in this vein. Whereas a detailed response to Dr.Ranjan and Dr. Chandra’s critique(1) of Alexander et al’s paper entitled ‘Rapid Tranquillisation ofviolent or agitated patients in a psychiatric emergency setting’(2) is theprerogative of the authors themselves, I feel I can add a few more points to the ongoing discussion.

Contemporary principles of evidence-based mental health care dictate that evidence emanating from systematic reviews of RCT’s and RCT’s ought to have greater bearing on clinical decisions than anecdotal clinical experience reports. A literature search on the topic of ‘rapid tranquillisation’ reveals surprising little research that has ever been done on such a common element of psychiatric practice. McAllister-Williams’ review article (3) (which dates prior to the formation of the TREC Collaborative Group (4)) describes the scarcity of good evidence to suggest any one treatment more than anything else. In fact, there has beenonly one study cited in that article that had a randomized controlled design (5). This trial compares haloperidol and droperidol, and as droperidol has dropped out of modern practice, it presents outdated evidence. In essence, unless tested within a randomized controlled design,we ought to be wary of clinicians proclaiming evidence for any treatment simply because ‘we use it’, ‘it works’ and ‘we use it on more than 9000 people a month’.

On a second point, there is indeed something to say about the simplicity of measures used in Alexander at al’s paper, or indeed even theearlier paper by the TREC Collaboration (4). I feel this adds to the valueof these studies, as it brings the trials closer to reality. When the on-call clinician, and when called upon such an instance on the wards, I would personally not quite bother with noting the ‘character’ of patient aggression, violence or agitation. Rapid treatment is precisely that- rapid, and measures have to be taken to de-escalate the situation swiftly and with appropriate care.

Furthermore, this debate has acquired new colours in recent years with the introduction and aggressive marketing of expensive atypical antipsychotics for acute agitation and aggression (6). Sponsored studies have surfaced with rapidity claiming evidence to beat all evidence. However, this too much be interpreted with caution as we haven’t tested good old haloperidol and lorazepam enough, and we are being told that IM Olanzapine is the best of all.

As the field of psychiatry advances, our role as scientists becomes subsumed in our role as clinicians. This involves critical appraisal and rigorous sifting and researching of evidence before accepting anything on face value. Now the common question dictating any treatment is ‘What is the evidence for it and how rigorously has it been obtained?’

References

1. Ranjan, S. & Chandra, P.,S. (2004) Rapid Tranquillisation in Psychiatric Emergency: Lorazepam vs. Haloperidol-Promethazine Mix. BritishJournal of Psychiatry Website. 25 August 2004. See link http://bjp.rcpsych.org/cgi/eletters/185/1/63

2. Alexander, J., Tharyan, P., Adams, C., John, T., Mol, C., & Philip, J. (2004) Rapid tranquillisation of violent or agitated patients in a psychiatric setting. British Journal of Psychiatry, 185, 63-69

3. TREC Collaborative Group (2003) Rapid Tranquillisation for agitated patients in emergency psychiatric rooms: a randomized trial of Midazolam vs. Haloperidol plus promethazine. British Medical Journal, 27 September 2003, 708-711

4. McAllister-Williams, R.H. & Ferrier, I. N. (2002) Rapid Tranquillisation: time for reappraisal of options for parenteral therapy. British Journal of Psychiatry, 180, 485-489

5. Resnick, M, Burton B. T. (1984) Droperidol vs. haloperidol in the initial management of acute agitated patients. Journal of Clinical Psychiatry, July; 45(7): 298-299

6. Wright, P., Birkett, M., David, S., R., Meehan, K., et al (2001) Double-Blind, Placebo-Controlled comparison of intramuscular Olanzapine and intramuscular Haloperidol in the treatment of acute agitation in Schizophrenia (2001) American Journal of Psychiatry, 158: (July) 1149-1151
... More

Conflict of interest: None Declared

Write a reply

Rapid Tranquilization In Psychiatric Emergency: Lorazepam Vs Haloperidol and Promethazine Mix

sanjeev ranjan, psychiatrist
25 August 2004

Dear EditorIt is important to develop cost effective and efficient methods of treatment in emergency psychiatry, specially in resource poor settings. Alexander et al (2004) in their article comparing two methods of rapid tranquilization conclude that the injectable haloperidol – promethazine mix is as effective as lorazepam and have also discussed that in India, the former is a more cost effective option.While acknowledging the findings of their study, we would like to make observations regarding the cost effectiveness angle and also a few methodological issues. The preferred combination for rapid tranquilizationat the two largest psychiatric centers in India i.e. Bangalore(National Institute of Mental Health and Neurosciences) and Ranchi (Central Institute of Psychiatry)(combined monthly outpatient attendance of > 9000) is that of haloperidol with lorazepam rather than the combination used in the study. This practice is guided by the existing literature as well as existing practice (Mcallister-Williams and Nicol Ferrier, 2002; Hughes and Kleespies, 2003). This combination is about 25% cheaper compared to the combination used in this study (CIMS, 2004). Since promethazine has both alpha-1 and dopaminergic antagonism its combination with haloperidol is more likely to produce hypotension and neuroleptic malignant syndrome in agitated patients who are often dehydrated and dyselectrolytemic. On the other hand use of lorazepam decreases the required dose of haloperidol. We hence feel that the combination used in the study for rapid tranquilization may not be the most cost effective or the most efficacious even in resource poor settings.Regarding the tools used, we feel that use of more aggression specific measures such as the Overt Aggression Scale (Coccaro et al, 1991) which assesses different aspects of aggression and its severity would have generated more specific results, which was not possible with the use of a more global and generic scale such as the CGI.

This study also shows that the combination injection produces sedation quicker than intramuscular lorazepam. However This finding shouldbe viewed in the light of following facts. The lorazepam group contained more manic patients, more patients having substance use or already on benzodiazepines (who could have developed tolerance to benzodiazepines), and more patients with marked or severe illness (which would necessitate ahigher dose of medication to control). Taken together these factors could contribute significantly to the results.

Sanjeev Ranjan

Prabha S. Chandra

REFERENCESAlexander, J., Tharyan, P., Adams, C. et al. (2004) Rapid tranquilization of violent or agitated patients in a psychiatric emergency setting. British Journal of Psychiatry, 185, 63-69.

CIMS (2004) CIMS-Updated prescribers’ handbook. July (update3), 203-236, Bangalore: Atmedica India.

Coccaro, E. F., Harvey, P.D., Kupsaw-Lawrence, E. et al (1991) Development of neuropharmacologically based behavioural assessments of impulsive aggressive behaviour. Journal of Neuropsychiatry and Clinical Neuroscience, 3, s44-51.

Hughes, D. H. and Kleespies, P. M. (2003) Treating aggression in the psychiatric emergency service. Journal of Clinical Psychiatry, 64 (suppl. 4), 10-15.

McAllister-Williams, R. H, and Nicol Ferrier, I., (2002) Rapid tranquillization: time for a reappraisal of options for parenteral therapy. The British Journal of Psychiatry 180: 485-489.
... More

Conflict of interest: None Declared

Write a reply

×

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *