Background: Acute opioid overdose is a common cause of admission in emergency department. In spite of the fact that naloxone is the main therapy for decades, there are controversies about the proper way of its use. This study aimed to compare two most recommended administration modes for naloxone.

Methods: In this single-blind clinical trial, 80 patients with methadone overdose syndrome were randomly divided into two equal groups. The patients in infusion group received a constant infusion of naloxone preparation while in the patients in PRN group, naloxone was administered only if needed clinically. Severity of withdrawal syndrome was evaluated after 30 min, 3 h, and 12 h of the treatments in both groups.

Results: Eighty patients completed the study (10 women and 70 men). Both groups were similar in terms of mean age, sex ratio, and the severity of intoxication. The severity of withdrawal symptom was significantly lower in the PRN group (P<0.001).

Conclusion: Naloxone administration as PRN mode lowers the rate and severity of withdrawal syndrome. It is recommended as the preferred mode of naloxone administration.