Gabrielle Agin-Liebes1, Andrew S Huhn2, Eric C Strain2, George E Bigelow2, Michael T Smith2, Robert R Edwards3, Valerie A Gruber4, D Andrew Tompkins5. 1. University of California, San Francisco, Department of Psychiatry and Behavioral Sciences, 401 Parnassus Ave, San Francisco, CA, 94143, USA; Zuckerberg San Francisco General Hospital, 1001 Potrero Ave, Ward 95, San Francisco, CA, 94110, USA. Electronic address: gabrielle.agin-liebes@ucsf.edu. 2. Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences, 4940 Eastern Avenue, Baltimore, MD, 21224, USA. 3. Harvard Medical School, Brigham and Women's Hospital, Department of Anesthesiology, Perioperative, and Pain Medicine, 75 Francis St, Boston, MA, 02115, USA. 4. University of California, San Francisco, Department of Psychiatry and Behavioral Sciences, 401 Parnassus Ave, San Francisco, CA, 94143, USA; Zuckerberg San Francisco General Hospital, 1001 Potrero Ave, Ward 95, San Francisco, CA, 94110, USA. 5. University of California, San Francisco, Department of Psychiatry and Behavioral Sciences, 401 Parnassus Ave, San Francisco, CA, 94143, USA; Zuckerberg San Francisco General Hospital, 1001 Potrero Ave, Ward 95, San Francisco, CA, 94110, USA. Electronic address: david.tompkins@ucsf.edu.
Abstract
OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVES: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Joao P De Aquino; Suprit Parida; Victor J Avila-Quintero; Jose Flores; Peggy Compton; Thomas Hickey; Oscar Gómez; Mehmet Sofuoglu Journal: Drug Alcohol Depend Date: 2021-09-22 Impact factor: 4.492