Double-blind, randomized study of nalmefene and naloxone in emergency department patients with suspected narcotic overdose

Study objectives: To compare the efficacy, safety, and withdrawal symptoms in emergency department patients with suspected narcotic overdose treated w ith nalmefene, an opioid antagonist with a 4- to 10-hour duration of action , with those treated with naloxone. Methods: Adults in 9 centers who would otherwise receive naloxone for alter ed consciousness levels were randomly assigned to receive intravenous study drug (1 mg nalmefene, or 2 mg nalmefene or 2 mg naloxone, double-blinded) every 5 minutes as needed for up to 4 doses in a 4-hour study. Outcomes wer e 20-minute and 4-hour posttreatment changes in respiratory rates, Neurobeh avioral Assessment Scale scores, Opioid Withdrawal Scale scores, and incide nces of adverse events. Results: Opioid positivity was recorded for 30 of 63 (1-mg nalmefene), 23 o f 55 (2-mg nalmefene), and 28, of 58 (naloxone) cases, 75% of whom also had nonopioid central nervous system depressants, Most patients received only 1 dose of study drug. Similar, clinically meaningful improvements in respir atory rates and Neurobehavioral Assessment Scale scores were seen with all treatments. No statistical differences in efficacy or withdrawal outcomes w ere seen between treatment groups, and no significant overall time-treatmen t interactions occurred, in either the entire patient group or among opioid -positive cases (P>.21, all comparisons). Adverse events occurred in 30.9% (2 mg nalmefene), 15.9% (1 mg nalmefene), and 15.5% (naloxone) of patients (P>.08); none were associated with morbidity. Conclusion: In this study of patients with varied potential causes of alter ed consciousness, nalmefene (1 mg and 2 mg) and naloxone (2 mg) appeared to be efficacious, safe, and to yield similar clinical outcomes.