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Safety of Naloxone in Opioid-Naïve Methadone Intoxicated Patients; a Case Series Study

Seyed Hamid Reza Shakeri, Hossein Hassanian-Moghaddam, Nasim Zamani



Introduction: Studies have shown that naloxone can cause behavioral changes in naïve normal volunteers. This study aimed to investigate the possible complications of naloxone in methadone-overdosed opioid-naïve patients.

Methods: In this pilot study, a total number of 20 opioid-naïve methadone-poisoned patients underwent naloxone challenge test to receive naltrexone. 0.2, 0.6, and 1.2 mg doses of naloxone were administered on minutes 0, 5, and 15-20. The patients were followed for 30 minutes after administration of naloxone and monitored for any upsetting signs and symptoms. Patients with clinical opiate withdrawal scale (COWS) lower than 5 were considered not addicted and the severity of patients’ symptoms was calculated using subjective opiate withdrawal syndrome (SOWS).

Results: 20 patients with mean age of 25.5±8.09 years were evaluated (70% female). Median ingested dose of methadone was 25 mg [IQR; 10 to 50 mg] and mean time interval between ingestion of methadone and naloxone challenge test was 7.1±4.9 hours. Fourteen patients reported some discomfort after administration of a mean dose of 1.7±0.5 mg of naloxone lasting for a maximum of four hours. The most common patients’ complaints were headache (45%) followed by nausea (20%), agitation (20%), abdominal pain (20%), and flushing (20%). Two (10%) mentioned severe panic attack and sensation of near-coming death. SOWS significantly correlated with female gender (p = 0.004) and time elapsed post methadone ingestion (p = 0.001).

Conclusion: It seems that naloxone is not a completely safe medication even in opioid-naïve patients, and administrating adjusted doses of naloxone even in opioid-naïve methadone intoxicated patients may be logical.


Naloxone; Substance Withdrawal Syndrome; Analgesics, Opioid; Drug-Related Side Effects and Adverse Reactions


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DOI: https://doi.org/10.22037/aaem.v8i1.535

DOI (PDF): https://doi.org/10.22037/aaem.v8i1.535.g709

DOI (HTML): https://doi.org/10.22037/aaem.v8i1.535.g780