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

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.