Methadone maintenance patients lack analgesic response to a cumulative intravenous dose of 32 mg of hydromorphone

• Published in: Drug and alcohol dependence 2021-09, Vol.226, p.108869-108869, Article 108869
• Main Authors: Agin-Liebes, Gabrielle, Huhn, Andrew S., Strain, Eric C., Bigelow, George E., Smith, Michael T., Edwards, Robert R., Gruber, Valerie A., Tompkins, D. Andrew
• Format: Article
• Language: English
• Subjects: Abuse; Adverse events; Analgesia; Analgesics; Analgesics, Opioid - adverse effects; Chronic pain; Critical incidents; Dosage; Drug abuse; Drug addiction; Drug Tolerance; Humans; Hydromorphone; Hydromorphone - adverse effects; Intravenous administration; Liability; Methadone; Methadone - adverse effects; Methadone maintenance; Narcotics; Opioid-Related Disorders - drug therapy; Opioids; Pain; Pain perception; Placebos; Population studies; Quantitative sensory testing; Sensory testing; Substance use disorder; Tolerance
• ISSN: 0376-8716; 1879-0046; 1879-0046
• DOI: 10.1016/j.drugalcdep.2021.108869

•The prevalence of individuals on methadone to treat opioid use disorder is rising.•Providing adequate acute pain management is a challenge for this patient population.•Methadone patients on 80−100 mg/day appear to be insensitive to the effects of 32 mg IV hydromorphone.•Methadone patients may require more efficacious opioid analgesics or non-opioid analgesics to achieve optimal acute pain relief. Acute pain management in patients with opioid use disorder who are maintained on methadone presents unique challenges due to high levels of opioid tolerance in this population. This randomized controlled study assessed the analgesic and abuse liability effects of escalating doses of acute intravenous (IV) hydromorphone versus placebo utilizing a validated experimental pain paradigm, quantitative sensory testing (QST). Individuals (N = 8) without chronic pain were maintained on 80−100 mg/day of oral methadone. Participants received four IV, escalating/incremental doses of hydromorphone over 270 min (32 mg total) or four placebo doses within a session test day. Test sessions were scheduled at least one week apart. QST and abuse liability measures were administered at baseline and after each injection. No significant differences between the hydromorphone and placebo control conditions on analgesic indices for any QST outcomes were detected. Similarly, no differences on safety or abuse liability indices were detected despite the high doses of hydromorphone utilized. Few adverse events were detected, and those reported were mild in severity. The findings demonstrate that methadone-maintained individuals are highly insensitive to the analgesic effects of high-dose IV hydromorphone and may require very high doses of opioids, more efficacious opioids, or combined non-opioid analgesic strategies to achieve adequate analgesia.