Study protocol for a randomised controlled trial of haloperidol plus promethazine plus chlorpromazine versus haloperidol plus promethazine for rapid tranquilisation for agitated psychiatric patients in the emergency setting (TREC-Lebanon)

Joseph E Dib, Clive E Adams, Werner Henry Ikdais, Elie Atallah, Hiba Edward Yaacoub, Tony Jean Merheb, Francois Kazour, Fouad Tahan, Georges Haddad, Marouan Zoghbi, Jocelyn Azar, Chadia Haddad, Souheil Hallit, Joseph E Dib, Clive E Adams, Werner Henry Ikdais, Elie Atallah, Hiba Edward Yaacoub, Tony Jean Merheb, Francois Kazour, Fouad Tahan, Georges Haddad, Marouan Zoghbi, Jocelyn Azar, Chadia Haddad, Souheil Hallit

Abstract

Background: Agitated and aggressive behaviours are common in the psychiatric setting and rapid tranquilisation is sometimes unavoidable. A survey of Lebanese practice has shown that an intramuscular haloperidol, promethazine and chlorpromazine combination is a preferred form of treatment but there are no randomised trials of this triple therapy. Methods: This is a pragmatic randomised trial. Setting - the psychiatric wards of the Psychiatric Hospital of the Cross, Jal Eddib, Lebanon. Participants - any adult patient in the hospital who displays an aggressive episode for whom rapid tranquilisation is unavoidable, who has not been randomised before, for whom there are no known contraindications. Randomisation - stratified (by ward) randomisation and concealed in closed opaque envelope by independent parties. Procedure - if the clinical situation arises requiring rapid tranquilisation, medical residents overseeing the patient will open a TREC-Lebanon envelope in which will be notification of which group of treatments should be preferred [Haloperidol + Promethazine + Chlorpromazine (HPC) or Haloperidol + Promethazine (HP)], along with forms for primary, secondary and serious adverse effects. Treatment is not given blindly. Outcome - primary outcome is calm or tranquil at 20 minutes post intervention. Secondary outcomes are calm/tranquil at 40, 60 and 120 minutes post intervention, asleep, adverse effects, use of straitjacket and leaving the ward. Follow-up will be up to two weeks post randomisation. Discussion: Findings from this study will compare the HPC versus HP combination used in Lebanon's psychiatry emergency routine practice. Trial registration: ClinicalTrials.gov NCT03639558. Registration date, August 21, 2018.

Keywords: Aggression; Agitation; Chlorpromazine; Emergency management; Haloperidol; Lebanon; Promethazine; Randomised Controlled Trial; Rapid Tranquilisation; Trial Protocol; Violence.

Conflict of interest statement

No competing interests were disclosed.

Copyright: © 2019 Dib JE et al.

Figures

Figure 1.. Flow diagram.
Figure 1.. Flow diagram.

References

    1. Tardiff K, Koenigsberg HW: Assaultive behavior among psychiatric outpatients. Am J Psychiatry. 1985;142(8):960–3. 10.1176/ajp.142.8.960
    1. Kaplan HI, Sadock BJ: Kaplan and Sadock's synopsis of psychiatry: Behavioral sciences/clinical psychiatry. Williams & Wilkins Co;1998.
    1. Treatment of schizophrenia 1999. The expert consensus guideline series. J Clin Psychiatry. 1999;60 Suppl 11:3–80.
    1. National Institute for Clinical Excellence: Short-term Management of Violent (Disturbed) Behaviour in Adult Psychiatric In-patient and Accident and Emergency Settings. Second Draft for Consultation. London: NICE;2004.
    1. Yildiz A, Sachs GS, Turgay A: Pharmacological management of agitation in emergency settings. Emerg Med J. 2003;20(4):339–346. 10.1136/emj.20.4.339
    1. Colaizzi J: Seclusion & restraint: A historical perspective. J Psychosoc Nurs Ment Health Serv. 2016;43(2):31–37. 10.3928/02793695-20050201-07
    1. Crespi TD: Restraint and seclusion with institutionalized adolescents. Adolescence. 1990;25(100):825–829.
    1. Fisher WA: Restraint and seclusion: a review of the literature. Am J Psychiatry. 1994;151(11):1584–1591. 10.1176/ajp.151.11.1584
    1. Saks ER: The Use of Mechanical Restraints in Psychiatric-Hospitals. Yale Law J. 1986;95(8):1836–1856.
    1. Allen MH, Currier GW, Hughes DH, et al. : The expert consensus guideline series. Treatment of behavioral emergencies. Postgrad Med. 2001; (Spec No):1–88; quiz 89-90.
    1. Wing J, Marriott S, Palmer C, et al. : Management of imminent violence: clinical practice guidelines to support mental health services.1998.
    1. Pilowsky LS, Ring H, Shine PJ, et al. : Rapid tranquillisation. A survey of emergency prescribing in a general psychiatric hospital. Br J Psychiatry. 1992;160:831–835. 10.1192/bjp.160.6.831
    1. Dib JE, Adams CE, Kazour F, et al. : Managing acutely aggressive or agitated people in a psychiatric setting: a survey in Lebanon. Med J Islam Repub Iran. 2018;32:60. 10.14196/mjiri.32.60
    1. Huf G, da Silva Freire Coutinho E, Fagundes HM, Jr, et al. : Current practices in managing acutely disturbed patients at three hospitals in Rio de Janeiro-Brazil: a prevalence study. BMC Psychiatry. 2002;2:4. 10.1186/1471-244X-2-4
    1. Huf G, Alexander J, Gandhi P, et al. : Haloperidol plus promethazine for psychosis-induced aggression. Cochrane Database Syst Rev. 2016;11:CD005146. 10.1002/14651858.CD005146.pub3
    1. TREC Collaborative Group: Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine. BMJ. 2003;327(7417):708–13. 10.1136/bmj.327.7417.708
    1. Huf G, Coutinho ES, Adams CE, et al. : TREC-Rio trial: a randomised controlled trial for rapid tranquillisation for agitated patients in emergency psychiatric rooms [ISRCTN44153243]. BMC Psychiatry. 2002;2(1):11. 10.1186/1471-244X-2-11
    1. Chan AW, Tetzlaff JM, Altman DG, et al. : SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200–207. 10.7326/0003-4819-158-3-201302050-00583
    1. El Laithy H, Abu-Ismail K, Hamdan K: Poverty, growth and income distribution in Lebanon. In. International Policy Centre for Inclusive Growth: International Policy Centre for Inclusive Growth;2008.
    1. World Health Organization: WHO - Aims report on mental health system in Lebanon. Beirut, Lebanon Ministry of Health Lebanon.2010.
    1. Berger EL: Mental Health Atlas 2005. J Nerv Ment Dis. 2007;195(4):358–358.
    1. World Health Organization: The Selection and Use of Essential Medicines: Report of the WHO Expert Committee, 2015 (including the 19th WHO Model List of Essential Medicines and the 5th WHO Model List of Essential Medicines for Children). World Health Organization;2015.
    1. Ahmed U, Jones H, Adams CE: Chlorpromazine for psychosis induced aggression or agitation. Cochrane Database Syst Rev. 2010; (4):CD007445. 10.1002/14651858.CD007445.pub2
    1. Adams CE, Awad GA, Rathbone J, et al. : Chlorpromazine versus placebo for schizophrenia. Cochrane Database Syst Rev. 2014; (1):CD000284. 10.1002/14651858.CD000284.pub3
    1. Abidi S, Bhaskara SM: From chlorpromazine to clozapine--antipsychotic adverse effects and the clinician's dilemma. Can J Psychiatry. 2003;48(11):749–755. 10.1177/070674370304801107
    1. Hedges D, Jeppson K, Whitehead P: Antipsychotic medication and seizures: a review. Drugs Today (Barc). 2003;39(7):551–557. 10.1358/dot.2003.39.7.799445
    1. Dold M, Samara MT, Li C, et al. : Haloperidol versus first-generation antipsychotics for the treatment of schizophrenia and other psychotic disorders. Cochrane Database Syst Rev. 2015;1(1):CD009831. 10.1002/14651858.CD009831.pub2
    1. Rasmussen SA, Rosebush PI, Mazurek MF: The Relationship Between Early Haloperidol Response and Associated Extrapyramidal Side Effects. J Clin Psychopharmacol. 2017;37(1):8–12. 10.1097/JCP.0000000000000637
    1. Adams CE, Bergman H, Irving CB, et al. : Haloperidol versus placebo for schizophrenia. Cochrane Database Syst Rev. 2013; (11):CD003082. 10.1002/14651858.CD003082.pub3
    1. van Harten PN, Hoek HW, Kahn RS: Acute dystonia induced by drug treatment. BMJ. 1999;319(7210):623–626. 10.1136/bmj.319.7210.623
    1. Huf G, Coutinho ES, Adams CE, et al. : Rapid tranquillisation in psychiatric emergency settings in Brazil: pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine. BMJ. 2007;335(7625):869. 10.1136/
    1. Cantisani C, Ricci S, Grieco T, et al. : Topical promethazine side effects: our experience and review of the literature. Biomed Res Int. 2013;2013:151509. 10.1155/2013/151509
    1. Lemmens P, Brecher M, Van Baelen B: A combined analysis of double-blind studies with risperidone vs. placebo and other antipsychotic agents: factors associated with extrapyramidal symptoms. Acta Psychiatr Scand. 1999;99(3):160–170. 10.1111/j.1600-0447.1999.tb00972.x
    1. Rummel-Kluge C, Komossa K, Schwarz S, et al. : Second-generation antipsychotic drugs and extrapyramidal side effects: a systematic review and meta-analysis of head-to-head comparisons. Schizophr Bull. 2012;38(1):167–177. 10.1093/schbul/sbq042
    1. Alomar MJ: Factors affecting the development of adverse drug reactions (Review article). Saudi Pharm J. 2014;22(2):83–94. 10.1016/j.jsps.2013.02.003
    1. National Institute for Health Care Excellence: Violence and Aggression: Short-Term Management in Mental Health, Health and Community Settings: Updated edition.2015.
    1. Altman DG: Confidence intervals for the number needed to treat. BMJ. 1998;317(7168):1309–1312. 10.1136/bmj.317.7168.1309
    1. SPSS MOD: SPSS (Statistical Package for the Social Sciens).2015.
    1. World Medical Association: World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA. 2013;310(20):2191–2194. 10.1001/jama.2013.281053
    1. European Parliament: Directive 2001/20/EC of the European Parliament and of the Council of 4 April 2001 on the approximation of the laws, regulations and administrative provisions of the member states relating to the implementation of good clinical practice in the conduct of clinical trials on medicinal products for human use. Med Etika Bioet. 2002;9(1–2):12–19.
    1. Nuffield Council: Nuffield Council on Bioethics. London;2000.
    1. Rebers S, Aaronson NK, van Leeuwen FE, et al. : Exceptions to the rule of informed consent for research with an intervention. BMC Med Ethics. 2016;17:9. 10.1186/s12910-016-0092-6
    1. Lesage P, Portenoy RK: Ethical challenges in the care of patients with serious illness. Pain Med. 2001;2(2):121–130. 10.1046/j.1526-4637.2001.002002121.x
    1. Roth LH, Appelbaum PS, Lidz CW, et al. : Informed consent in psychiatric research. Rutgers Law Rev. 1987;39(2–3):425–441.
    1. Helsinki TDo: Ethical principles for medical research involving human subjects.2013.
    1. Dib J: TREC-Lebanon Protocol. OSF. 2019. 10.17605/

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