Randomized trialOpioid use disorder1999
Kaplan 1999: nalmefene vs naloxone for suspected overdose
Kaplan JL, Marx JA, Calabro JJ, et al. Double-blind, randomized study of nalmefene and naloxone in emergency department patients with suspected narcotic overdose
What it found
Nalmefene at 1 mg or 2 mg and naloxone at 2 mg, given into a vein, led to similar and clinically meaningful improvements in breathing and alertness in emergency patients with suspected opioid overdose. There were no statistical differences between the drugs in how well they worked or in withdrawal symptoms.
- Opioid-positive, 1 mg nalmefene
- 30 of 63
- Opioid-positive, 2 mg nalmefene
- 23 of 55
- Opioid-positive, naloxone
- 24 of 58
- Opioid-positive who also had other sedatives
- 75%
What they tested
Adults at 9 centers who would otherwise have been given naloxone for reduced consciousness were randomly assigned to 1 mg nalmefene, 2 mg nalmefene or 2 mg naloxone into a vein. Neither patients nor staff knew which. The dose could be repeated every 5 minutes, up to 4 doses, over a 4-hour study.
Nalmefene is an opioid blocker related to naltrexone that lasts 4 to 10 hours. Researchers compared changes in breathing rate, a neurological alertness score and an opioid withdrawal score at 20 minutes and 4 hours, along with side effects.
What they found
Testing found opioids in 30 of 63 people on 1 mg nalmefene, 23 of 55 on 2 mg nalmefene and 24 of 58 on naloxone. Of these, 75% had also taken other drugs that depress the nervous system. Most patients needed only 1 dose.
All three treatments brought similar, clinically meaningful improvements in breathing rate and alertness scores. No statistical differences in effectiveness or withdrawal were found between the groups, either in all patients or in those who tested positive for opioids.
Side effects occurred in 30.9% on 2 mg nalmefene, 15.9% on 1 mg nalmefene and 15.5% on naloxone, a difference that was not statistically significant. None were linked to further illness or harm.
Limits
- Fewer than half of patients in each group tested positive for opioids, and most of those had also taken other sedating drugs, so the trial mixed many causes of reduced consciousness.
- The study lasted 4 hours, so it couldn't show whether nalmefene's longer action (4 to 10 hours) made a difference later on.
- It tested injected doses in hospital, not the nasal spray or auto-injector forms sold today.
What it means if you're considering naltrexone
This trial is about reversing an overdose, not about treating alcohol or opioid use disorder. Nalmefene is the opioid blocker the site covers alongside naltrexone; in the US it is now sold as Opvee spray and the Zurnai auto-injector for overdose, and in Europe as Selincro tablets for cutting down drinking.
For overdose, this trial found nalmefene and naloxone worked about the same over 4 hours in a mixed group of emergency patients.
Frequently asked questions
Is nalmefene better than naloxone for overdose?
In this emergency department trial, nalmefene at 1 mg or 2 mg and naloxone at 2 mg gave similar improvements in breathing and alertness, with no statistical difference in effectiveness or withdrawal.
The paper
Kaplan JL, Marx JA, Calabro JJ, et al. Double-blind, randomized study of nalmefene and naloxone in emergency department patients with suspected narcotic overdose. Ann Emerg Med. 1999;34(1):42-50. doi:10.1016/s0196-0644(99)70270-2
Read the paperdoi:10.1016/s0196-0644(99)70270-2
We wrote this page from the paper's published abstract, and the study's numbers here come from there. Updated October 17, 2026.
Medical disclaimer
This page is for information only and is not medical advice, diagnosis, or treatment. Don't start, stop, or change any medicine — including naltrexone — without your prescriber. Naltrexone must not be used by people taking opioid pain medicines, people dependent on opioids, or people in opioid withdrawal (FDA label). In an emergency call 911; for crisis support call or text 988. Full medical disclaimer.