Background: Patients with intoxication from long-acting opioids face significant risk of recurrent or delayed respiratory arrest despite standard initial treatment with naloxone. Due to their long half-lives, naltrexone and buprenorphine may have therapeutic potential to prevent or reverse respiratory/CNS depression in opioid-naïve and opioid-dependent patients, respectively. The talk will present the results of two randomized trials in opioid-intoxicated patients.

Methods: In Trial 1, Methadone-poisoned patients (n=54) were administered naltrexone (50 mg) after initial naloxone treatment. In Trial 2, patients with respiratory depression(n=85) were randomized to receive naloxone (titrated doses) versus lower or higher doses of buprenorphine (10 μg/kg or 15 μg/kg). Patients were monitored for frequency of respiratory depression.

Results: In Trial 1, the incidence of respiratory depression was significantly reduced in patients who had received naltrexone treatment. In Trial 2, 55/56 (98%) patients who received buprenorphine had rapid reversal of respiratory depression, which persisted for at least 12 hours. Naloxone was effective in 28/29 (97%) patients, but often required very high titrated doses (thus delaying time to response) and prolonged infusions. Intubation (8/29 or 28% vs. 5/56 or 9%) and opioid withdrawal (15/29 or 52% vs. 7/56 or 13%) were less common with buprenorphine treatment.

Conclusion: Naltrexone (in opioid-naïve patients) and buprenorphine (in opioid-dependent patients) appear to be potentially safe and effective alternatives to naloxone treatment.

My presented study was internally funded by Shahid Beheshti University of Medical Sciences.

Presentation slides: Naltrexone and buprenorphine for the reversal of overdose from long-acting opioids: Iranian experience