Effects of Intramuscular Midazolam and Lorazepam on Acute Agitation in Non-Elderly Subjects – A Systematic Review

Abstract

Introduction

Benzodiazepines are commonly used for the treatment of acute agitation in a psychiatric setting.

Methods

We searched MEDLINE, EMBASE, PsycINFO, and the Cochrane Central Register of Controlled Trials (CENTRAL) for relevant publications. Randomized trials evaluating intramuscular (IM) midazolam or lorazepam given as monotherapy or as add-on treatment, with more than 10 patients aged 18–65 years, conducted in a psychiatric setting, and published between January 1, 1980, and February 3, 2016, were included.

Results

16 studies from a search result of 5 516 studies were included. In total, 577 patients were treated with lorazepam IM 2–4 mg, and 329 patients were treated with midazolam IM 5–15 mg.

Discussion

It is unclear whether lorazepam IM or midazolam IM is as efficacious as an antipsychotic IM. It is a bit more certain that the combination of benzodiazepines IM and a low dose antipsychotic IM is more efficacious than the benzodiazepine and the antipsychotic alone. However, there is no doubt that benzodiazepines are less likely to be associated with treatment emergent side effects, as compared to antipsychotics.

Key words

agitation - antipsychotics - lorazepam - midazolam

• References

• 1 Paso E, Health B, Drive H. World Health Organization Schedules for Clinical Assessment in Neuropsychiatry: Version 2.0. Geneva: Intelligence; 2002
• 2 Marder SR. A review of agitation in mental illness: Treatment guidelines and current therapies. J Clin Psychiatry. 2006; 67: 13-21
• 3 Zeller SL, Rhoades RW. Systematic reviews of assessment measures and pharmacologic treatments for agitation. Clin Ther 2010; 32: 403-425
• 4 Dundee JW. Advantages and problems with benzodiazepine sedation. Anesth Prog 1992; 39: 132-137
• 5 Stewart SA. The effects of benzodiazepines on cognition. J Clin Psychiatry 2005; 66: 9-13
• 6 Uzun S, Kozumplik O, Jakovljević M. et al. Side effects of treatment with benzodiazepines. Psychiatr Danub 2010; 22: 90-93
• 7 Vgontzas AN, Kales A, Bixler EO. Benzodiazepine side effects: role of pharmacokinetics and pharmacodynamics. Pharmacology 1995; 51: 205-223
• 8 Gahr M, Eller J, Connemann B. et al. Subjective Reasons for Non-Reporting of Adverse Drug Reactions in a Sample of Physicians in Outpatient Care. Pharmacopsychiatry 2016; 49: 57-61
• 9 Gillies D, Beck A, Mccloud A. et al. Benzodiazepines for psychosis-induced aggression or agitation (Review). Library (Lond) 2010; 4-6
• 10 Hung OR, Dyck JB, Varvel J. et al. Comparative absorption kinetics of intramuscular midazolam and diazepam. Can J Anaesth 1996; 43: 450-455
• 11 Licht R. Experience with benzodiazepines in the treatment of mania. In: Modigh K, Roback OH, Vestergaard P. (eds.). Anticonvulsants in Psychiatry. Petersfield, UK: Wrightson Biomedical Publishing; 1994: 37-55
• 12 Reus VI, Fochtmann LJ, Eyler E. et al. The American Psychiatric Association Practice Guideline on the Use of Antipsychotics to Treat Agitation Or Psychosis in Patients with Dementia. Am J Psychiatry 2016; 173: 543-546
• 13 Kishi T, Matsunaga S, Iwata N. Intramuscular olanzapine for agitated patients: a systematic review and meta-analysis of randomized controlled trials. J Psychiatr Res 2015; 68: 198-209
• 14 Tiihonen J, Mittendorfer-Rutz E, Torniainen M. et al. Mortality and cumulative exposure to antipsychotics, antidepressants, and benzodiazepines in patients with schizophrenia: An observational follow-up study. Am J Psychiatry 2016; 173: 600-606
• 15 Kurko TAT, Saastamoinen LK, Tahkapaa S. et al. Long-term use of benzodiazepines: definitions, prevalence and usage patterns – a systematic review of register-based studies. Eur Psychiatry 2015; 30: 1037-1047
• 16 Taipale H, Koponen M, Tanskanen A. et al. Long-term use of benzodiazepines and related drugs among community-dwelling individuals with and without Alzheimer’s disease. Int Clin Psychopharmacol 2015; 30: 202-208
• 17 Van Der Bijl P, Roelofse JA. Disinhibitory reactions to benzodiazepines: a review. J Oral Maxillofac Surg 1991; 49: 519-523
• 18 Smith BD, Salzman C. Do benzodiazepines cause depression?. Hosp Community Psychiatry 1991; 42: 1101-1102
• 19 Busto U, Sellers EM, Naranjo CA. et al. Withdrawal reaction after long-term therapeutic use of benzodiazepines. N Engl J Med 1986; 315: 854-859
• 20 Salzman C, Solomon D, Miyawaki E. et al. Parenteral lorazepam versus parenteral haloperidol for the control of psychotic disruptive behavior. J Clin Psychiatry 1991; 52: 177-180
• 21 Foster S, Kessel J, Berman ME. et al. Efficacy of lorazepam and haloperidol for rapid tranquilization in a psychiatric emergency room setting. Int Clin Psychopharmacol 1997; 12: 175-179
• 22 Meehan K, Zhang F, David S. et al. A double-blind, randomized comparison of the efficacy and safety of intramuscular injections of olanzapine, lorazepam, or placebo in treating acutely agitated patients diagnosed with bipolar mania. J Clin Psychopharmacol 2001; 21: 389-397
• 23 Alexander J, Tharyan P, Adams C. et al. Rapid tranquillisation of violent or agitated patients in a psychiatric emergency setting: pragmatic randomised trial of intramuscular lorazepam v. haloperidol plus promethazine. Br J Psychiatry 2004; 185: 63-69
• 24 Currier GW, Chou JCY, Feifel D. et al. Acute treatment of psychotic agitation: a randomized comparison of oral treatment with risperidone and lorazepam versus intramuscular treatment with haloperidol and lorazepam. J Clin Psychiatry 2004; 65: 386-394
• 25 Huang CLC, Hwang TJ, Chen YH. et al. Intramuscular olanzapine versus intramuscular haloperidol plus lorazepam for the treatment of acute schizophrenia with agitation: an open-label, randomized controlled trial. J Formos Med Assoc 2015; 114: 438-445
• 26 Garza-Trevino ES, Hollister LE, Overall JE. et al. Efficacy of combinations of intramuscular antipsychotics and sedative-hypnotics for control of psychotic agitation. Am J Psychiatry 1989; 146: 1598-1601
• 27 Battaglia J, Moss S, Rush J. et al. Haloperidol, lorazepam, or both for psychotic agitation? A multicenter, prospective, double-blind, emergency department study. Am J Emerg Med 1997; 15: 335-340
• 28 Bieniek SA, Ownby RL, Penalver A. et al. A double-blind study of lorazepam versus the combination of haloperidol and lorazepam in managing agitation. Pharmacotherapy 1998; 18: 57-62
• 29 Veser FH, Veser BD, McMullan JT. et al. Risperidone versus haloperidol, in combination with lorazepam, in the treatment of acute agitation and psychosis: a pilot, randomized, double-blind, placebo-controlled trial. J Psychiatr Pract 2006; 12: 103-108
• 30 Wyant M, Diamond BI, O’Neal E. et al. The use of midazolam in acutely agitated psychiatric patients. Psychopharmacol Bull 1990; 26: 126-129
• 31 Gisele Huf, Evandro SF, Coutinho CEA. Rapid tranquillisation for agitated patients in emergency psychiatric rooms: a randomised trial of midazolam versus haloperidol plus promethazine. BMJ 2003; 327: 708-713
• 32 Martel M, Sterzinger A, Miner J. et al. Management of acute undifferentiated agitation in the emergency department: a randomized double-blind trial of droperidol, ziprasidone, and midazolam. Acad Emerg Med 2005; 12: 1167-1172
• 33 Mantovani C, Labate CM, Sponholz A. et al. Are low doses of antipsychotics effective in the management of psychomotor agitation? A randomized, rated-blind trial of 4 intramuscular interventions. J Clin Psychopharmacol 2013; 33: 306-312
• 34 Isbister GK, Calver LA, Page CB. et al. Randomized controlled trial of intramuscular droperidol versus midazolam for violence and acute behavioral disturbance: the DORM study. Ann Emerg Med 2010; 56: 392-401
• 35 Nobay F, Simon BC, Levitt MA. et al. A prospective, double-blind, randomized trial of midazolam versus haloperidol versus lorazepam in the chemical restraint of violent and severely agitated patients. Acad Emerg Med 2004; 11: 744-749