Running title: surveying prescribing patterns in acute agitation Introduction
2. Differences in medication classes
Gender (1.601,df=1,p=0.201), age (11.034,df=8,p=0,200) and caseload ( 0.597,df=1,p=0.440) did not produce significant associations with choice of medication class. We did find significant associations for type of hospital ( 22.536,df=2,p<0,001) and type of doctor, psychiatrist or emergency doctor ( 16.886,df=1,p<0.001).
Use of guidelines and monitoring for efficacy and safety
Guidelines are not frequently used. Only 26.4 % reports the use of guidelines. This can be an individual set of recommendations ( 16.4%), a recommendation issued by a national professional society (4.5 %) or a published guideline (5.5 %).
The majority of respondents (94.5%) used only clinical evaluations to monitor the effect of the rapid tranquilisation.
Discussion
Agitation is a frequently encountered clinical condition by psychiatrists and emergency doctors since two third of respondents have a maximum of 10 cases per month in treatment. To our knowledge, there are no reports on the prevalence of acute agitation in other countries with which to compare .
In the total sample, antipsychotics are ranked first choice and benzodiazepines second choice when all respondents in the survey are considered. In non-secluded patients, preference is given to olanzapine and lorazepam. In secluded patients, who arguably demonstrate higher degrees of agitation compared to non-secluded patients, clothiapine and droperidol are prescribed most often. This seems in line with a recent consensus statement of the psychopharmacology workgroup of the American Association for Emergency Psychiatry 21 where antipsychotics – and in particular olanzapine or risperidone – are recommended as first-line management of acute agitation. However, this report does not differentiate patients according to their level of agitation, as is the case in our study. On the basis of a non-systematic review of the literature, Bak et al. 22 also advocate olanzapine and lorazepam, although the authors recommend to use lorazepam only in non-psychotic agitation. In addition, in a review of the literature from the period 1960-2000 Battaglia et al. 23 , found that most evidence for a safe and effective treatment of acute agitation was Haloperidol, Olanzapine and Lorazepam. This recommendation is also supported in the UK National Institute for Health and Care Excellence [NICE]guidelines on acute agitation 24.
It is surprising that our respondents are not in favour of zuclopenthixol as drug of choice for agitated patients. In contrast with this, the long acting form of zuclopenthixol is well-favoured, especially in secluded patients. This is not in line with earlier mentioned recent recommendations found in the literature
21,22.
Combinations of drugs are most frequently used in secluded patients. Given the lower proportion of respondents that use step-up regimens in secluded patients, it can be concluded that in this group a combination of drugs is the most prevalent procedure, which is in line with what is found in other studies
10,12, 16-20.
An interesting finding is that in non-secluded and secluded patients, a significant difference is found for the type of hospital when medication preferences ( and ipso facto medication class) is considered. For secluded patients, this result is also significant when type of respondent is taken into consideration. To our knowledge, this distinction is never made in earlier prevalence studies although it seems relevant to do so. Psychiatrists and emergency doctors have different education and – in Belgium – are approached with prescribing information by different pharmaceutical companies. It can be arguedthat this practice has an effect on which drug is prescribed, certainly in the context of our finding that most respondents never use any published guidelines, nor in selecting a drug or monitoring effect.
An explanation for our finding of the sparse use of monitoring - at least for assessment of efficacy of a treatment - is given in a recent systematic review by Zeller and colleagues who reported a similar observation 25. The authors hypothesize that, although agitation is a common behavioural emergency, there is a lack of easy-to-administer treatments that could improve treatment quality or predict treatment effects.
Although Flanders’ practice is close to what is advised in the literature, there remains a lack of research evaluating the clinical efficacy of antipsychotics and benzodiazepines for acute agitation. Both medication classes seem to be effective but, in the presence of limited available data from well designed pharmaceutical trials, recommendations are still largely based on either consensus statements or observational data.
Moreover, it is of great concern that there is a substantial lack of assessment tools that measure the effect of treatment – preferably directly in the moment and not post hoc through an evaluation by a caregiver.
Conclusion
Our results show that real prescription practice in Flanders (Belgium) in acute agitation is more or less following published recommendations. Prescription habits differ however accordingly to medical specialty, probably because most of the information on prescribing reaches the doctor via pharmaceutical companies andbecause of the sparse use of guidelines. However, it cannot be expected that doctors use a standardised guideline as there is still a lack of primary studies and assessment techniques for efficacy in this clinical field.
References
1. Allen MH, Currier GW. Use of restraints and pharmacotherapy in academic psychiatric emergency services. Gen Hosp Psychiatry. 2004;26(1):42-49.
2. Marco CA, Vaughan J. Emergency management of agitation in schizophrenia. Am J Emerg Med. 2005;23(6):767-776.
3. Huf G, Alexander J, Allen MH. Haloperidol plus promethazine for psychosis induced aggression. Cochrane Database Syst Rev. 2005;(1):CD005146.
4. Marco CA, Vaughan J. Emergency management of agitation in schizophrenia. Am J Emerg Med. 2005;23(6):767-776.
5. D’Amore J, Hung O, Chiang W, Goldfrank L. The epidemiology of the homeless population and its impact on an urban emergency department. Acad Emerg Med. 2001;8(11):1051-1055.
6. Zun LS, Downey LV. Level of agitation of psychiatric patients presenting to an emergency department. Prim Care Companion J Clin Psychiatry. 2008;10(2):108-113.
7. Deksnytė A, Aranauskas R, Budrys V, Kasiulevičius V, Sapoka V. Delirium: its historical evolution and current interpretation.
Eur J Intern Med. 2012 Sep;23(6):483-6.
8. Jiska Cohen-Mansfield, Marcia S. Marx and Alvin S. Rosenthal. A Description of Agitation in a Nursing Home. J Gerontol (1989) 44 (3): M77-M84.
9. Marder, SR. A review of agitation in mental illness: treatment guidelines and current therapies. The Journal of Clinical Psychiatry [2006, 67 Suppl 10:13-21]
10. Gisele Huf, Evandro SF Coutinho and Clive E Adams. TREC-Rio trial: a randomised controlled trial for rapid tranquillisation for agitated patients in emergency psychiatric rooms [ISRCTN44153243]. BMC Psychiatry 2002, 2:11
11. Jacob Alexander, Prathap Tharyan, Clive Adams,Thomas John, Carina Mol,Joncy Philip. Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting. Pragmatic randomised trial of intramuscular lorazepam v. haloperidol plus promethazine. The British Journal of Psychiatry (2004) 185: 63-69 doi: 10.1192/bjp.185.1.63
12. G Huf, CE Adams. Rapid tranquillisation in psychiatric emergency settings in Brazil: pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine. BMJ 2007;335:869
13. Ira D Glick, Stephen R Murray, Priya Vasudevan, Stephen R Marder, Rona J Hue. Treatment with atypical antipsychotics:
new indications and new populations . Journal of Psychiatric Research Volume 35, Issue 3, May–June 2001, Pages 187–191 14. Battaglia, John. Pharmacological Management of Acute Agitation Drugs, Volume 65, Number 9, 2005 , pp. 1207-1222(16) 15. De Fruyt J, Demyttenaere K (2004) Rapid tranquilization: new approaches in the emergency treatment of behavioral
disturbances. Eur Psychiatry 19(5), 243-249.
16. Allen, M.H., Currier, G.W., (2004) Use of restraints and pharmacotherapy in academic psychiatric emergency services. Gen.
Hosp. Psychiatry 26(1), 42-49
17. Pilowski, L.S., Ring, H., Shine, P.J. et al. (1992) Rapid tranquilisation. A survey of emergency prescribing in a general psychiatric hospital. Br. J. Psychiatry 160,831-835
18. James, B.O. (2011) Rapid tranquilisation agents for severe behavioural disturbance: a survey of African psychiatrist prescription patterns. Trop. Doct 41(1), 49-50
19. Huf, G., Coutinho, E., Fagundes, H. et al., (2002) Current practices in managing acutely disturbed patients at three hospitals in Rio de Janeiro-Brazil: a prevalence study. BMC Psychiatry, 2, 4-
20. Binder, R.L., McNiel, D.E. (1999) Emergency Psychiatry: contemporary practices in managing acutely violent patients in 20 psychiatric emergency rooms. Psychiatr. Serv.50, 1553-1554.
21. Wilson, M.P., Pepper, D., Currier, G.W. et al. (2012) The psychopharmacology of agitation: consensus statement of the American Association of Emergency Psychiatry, project BETA psychopharmacology workgroup. West J Emerg Med, 13(1):
26-34
22. Bak, M., van Os, J., Marcelis, M (2011) Rapid tranquillisation; review of the literature and recommendations. Tijdschr Psychiatr 53(10):727-737
23. Battaglia, J. (2005) Pharmacological management of acute agitation. Drugs, 65(9), 1207-1222.
24. NICE, (2005) NICE guideline on “ the short-term management of disturbed and violent behaviour in inpatient psychiatric settings and emergency departments”. Available at : http://guidance.nice.org.uk/CG25 . Accessed, July 4, 2013.
25. Zeller, S.L., Rhoades, R.W. ( 2010) Systematic reviews of assessment measures and pharmacologic treatments for agitation.
Clin. Ther. 32(3), 403-425.
Correspondence
Dr Chris Bervoets Psychiatrist
Psychiatric Intensive Care Unit PZ OLV Brugge
Collaborative Antwerp Psychiatric Research Institute (CAPRI)