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Patients with methamphetamine toxicity often present to the emergency department (ED) agitated, violent and psychotic. To determine the efficacy of a benzodiazepine versus a butyrophenone for chemical restraint we conducted a prospective, randomized study at a large urban university ED between January 1995 and January 1997. Patients were randomized to receive either lorazepam or droperidol intravenously. A 6-point sedation scale was devised, with 6 representing extreme agitation and 1 deep sleep. Sedation scores were recorded at time 0, 5,10, 15, 30 and 60 min. Vital signs were recorded at time 0 and at 60 min. If sedation was inadequate, repeat dosages of each drug could be repeated at 30 min. Toxicology screen, ethanol and creatinine phosphokinase levels were obtained. A total of 146 patients were evaluated. Seventyfour patients received lorazepam and 72 received droperidol. Both drugs had similar sedation profiles at 5 min. Patients receiving droperidol had significantly improved sedation scores at times 10, 15, 30 and 60 min than lorazepam (p<0.001). More repeat doses of lorazepam were given (26) than droperidol (6) at 30 min. Both drugs produced significant reductions in pulse, systolic blood pressure, respiratory rate, and temperature over 60 min. We conclude droperidol produces a more rapid and profound sedation than lorazepam for methamphetamine toxicity. Lorazepam is more likely to require repeat dosing than droperidol.