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: Frequently Asked Question. Available from: http://naloxoneinfo.org/sites/default/files/Frequently%20Asked%20Questions-Naloxone_EN.pdf.
Naloxone Side Effects. Available from: https://www.drugs.com/sfx/naloxone-side-effects.html.
Cohen M, Cohen R, Pickar D, Weingartner H, Murphy D, Bunney JR W. Behavioural effects after high dose naloxone administration to normal volunteers. The Lancet. 1981;318(8255):1110.
Aghabiklooei A, Hassanian-Moghaddam H, Zamani N, Shadnia S, Mashayekhian M, Rahimi M, et al. Effectiveness of naltrexone in the prevention of delayed respiratory arrest in opioid-naive methadone-intoxicated patients. BioMed Research International. 2013;2013.
Hamdi H, Hassanian-Moghaddam H, Hamdi A, Zahed NS. Acid-base disturbances in acute poisoning and their association with survival. Journal of critical care. 2016;35:84-9.
Khosravi N, Zamani N, Hassanian-Moghaddam H, Ostadi A, Rahimi M, Kabir A. Comparison of Two Naloxone Regimens in Opioid-dependent Methadone-overdosed Patients: A Clinical Trial Study. Current clinical pharmacology. 2017;12(4):259-65.
Ostadi A, Zamani N, Hassanian-Moghaddam H, Khosravi N, Shadnia S. Comparison of 2 Naltrexone Regimens in the Maintenance Therapy of Acute Methadone Overdose in Opioid-Naïve Patients: A Randomized Controlled Trial. Crescent Journal of Medical and Biological Sciences. 2019;6(1):1-5.
Clinical opiate withdrawal scale. Available from: https://www.drugabuse.gov/sites/default/files/files/ClinicalOpiateWithdrawalScale.pdf.
Subjective opiate withdrawal scale. Available from: https://www.asam.org/docs/default-source/education-docs/sows_8-28-2017.pdf?sfvrsn=f30540c2_2.
Naloxone. Available from: https://livertox.nih.gov/Naloxone.htm.
Mowry JB, Spyker DA, Brooks DE, Zimmerman A, Schauben JL. 2015 Annual Report of the American Association of Poison Control Centers’ National Poison Data System (NPDS): 33rd Annual Report. Clinical Toxicology. 2016;54(10):924-1109.