Intravenous midazolam-droperidol combination, droperidol or olanzapine monotherapy for methamphetamine-related acute agitation: subgroup analysis of a randomized controlled trial

Addiction. 2017 Jul;112(7):1262-1269. doi: 10.1111/add.13780. Epub 2017 Feb 28.

Abstract

Aim: To examine the efficacy and safety of (1) midazolam-droperidol versus droperidol and (2) midazolam-droperidol versus olanzapine for methamphetamine-related acute agitation.

Design and setting: A multi-centre, randomized, double-blind, controlled, clinical trial was conducted in two Australian emergency departments, between October 2014 and September 2015.

Participants: Three hundred and sixty-one patients, aged 18-65 years, requiring intravenous medication sedation for acute agitation, were enrolled into this study. We report the results of a subgroup of 92 methamphetamine-affected patients.

Intervention and comparator: Patients were assigned randomly to receive either an intravenous bolus of midazolam 5 mg-droperidol 5 mg combined, droperidol 10 mg or olanzapine 10 mg. Two additional doses were administered, if required: midazolam 5 mg, droperidol 5 mg or olanzapine 5 mg, respectively.

Measurements: The primary outcome was the proportion of patients sedated adequately at 10 minutes. Odds ratios with 95% confidence intervals (ORs, 95% CI) were estimated.

Findings: The baseline characteristics of patients in the three groups were similar. At 10 minutes, significantly more patients in the midazolam-droperidol group [29 of 34 (85.3%)] were sedated adequately compared with the droperidol group [14 of 30 (46.7%), OR = 6.63, 95% CI = 2.02-21.78] or with the olanzapine group [14 of 28 (50.0%), OR 5.80, 95% CI = 1.74-19.33]. The number of patients who experienced an adverse event (AE) in the midazolam-droperidol, droperidol and olanzapine groups was seven of 34, two of 30 and six of 28, respectively. The most common AE was oxygen desaturation.

Conclusion: A midazolam-droperidol combination appears to provide more rapid sedation of patients with methamphetamine-related acute agitation than droperidol or olanzapine alone.

Keywords: Droperidol; emergency care; methamphetamine; midazolam; olanzapine; psychomotor agitation; sedation.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Aged
  • Akathisia, Drug-Induced / drug therapy*
  • Australia
  • Benzodiazepines / administration & dosage
  • Benzodiazepines / therapeutic use*
  • Dopamine D2 Receptor Antagonists / therapeutic use
  • Double-Blind Method
  • Droperidol / administration & dosage
  • Droperidol / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Humans
  • Hypnotics and Sedatives / therapeutic use
  • Injections, Intravenous
  • Male
  • Methamphetamine / adverse effects*
  • Midazolam / administration & dosage
  • Midazolam / therapeutic use*
  • Middle Aged
  • Olanzapine
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Treatment Outcome
  • Young Adult

Substances

  • Dopamine D2 Receptor Antagonists
  • Hypnotics and Sedatives
  • Serotonin Uptake Inhibitors
  • Benzodiazepines
  • Methamphetamine
  • Olanzapine
  • Droperidol
  • Midazolam