Abuse Potential in Extended-Release Oxymorphone and Controlled-Release Oxycodone

National Harbor, Maryland—A randomized, double-blind, placebo-controlled study found that healthy, nondependent, recreational opioid users who took single oral doses of extended-release oxymorphone may be at a lower risk for potentially abusing opioids than those who took equal doses of controlled-release oxycodone. The oxymorphone group had significantly less drug liking, lower positive subjective effects, and less cognitive and psychomotor impairment. The results were presented at the AAPM meeting during a poster presentation titled Drug Liking and Cognitive/Psychomotor Impairment with Extended-Release Oxymorphone versus Controlled-Release Oxycodone. According to the authors, prescribing opioids to noncancer patients who suffer from chronic pain concerns some people who cite the recent increased use of therapeutic and illicit opioids. They worry that the patients may abuse or become addicted to opioids. To determine the potential for abuse, researchers have assessed patients’ drug liking as well as their potential for cognitive and psychomotor performance impairment. In the 2-phase, 5-treatment, 10-sequence, crossover study, the authors enrolled patients between 18 and 55 years of age who had used opioids on a nonmedical basis ≥10 times during their lifetime. The eligibility requirements also included taking ≥1 opioid for a nonmedical use within ≤1 year and using an oral intact modified-release opioid on a recreational basis ≥3 times during their lives. In the qualification phase, patients received 8 mg of blinded hydromorphone plus placebo in a crossover fashion. They were randomized in the treatment phase if they demonstrated a ≥10% difference between drugs on a drug liking scale and acceptable responses on other scales. During the treatment phase, patients received blinded, single, intact, oral doses of the following drugs in 1 of 10 sequences with 7 to 21 days of separation: 15 mg of extended-release oxymorphone, 30 mg of extended-release oxymorphone, 30 mg of controlled-release oxycodone, and 60 mg of controlled-release oxycodone. During the trial, patients could not use recreational drugs or binge drink, and they were also required to abstain from alcohol for ≥48 hours before each phase and from taking monoamine oxidase inhibitors within 14 days of the study. Women were required to abstain from sex or use contraceptives during the study as well as ≥30 days before and after the study. Of the 78 patients in the qualification phase, 54 showed discrimination between the drug and placebo and 41 were randomized during the treatment phase. Of those 41 patients, 40 received ≥1 dose of study medication and 35 completed each of the treatments. The drugs had a dose-response relationship for mean plasma concentrations. At equal doses, extended-release oxymorphone had a significantly lower maximum pharmacodynamic effect for current drug liking, cumulative drug liking, and subjective drug value compared with controlled-release oxycodone (P<.01 in each case). Extended-release oxymorphone also demonstrated significantly lower scores on the good effects visual analog scale as well as the euphoria and high effect scales. In cognitive pharmacodynamic measures, extended-release oxymorphone had less impairment in accuracy/attention, manual tracking, and reaction time. During the treatment phase, there were no deaths, serious adverse events (AEs), or significant AEs. In the oxymorphone group, 59.5% of patients taking 15-mg doses and 73.7% of patients taking 30-mg doses experienced an AE. In the oxycodone group, 87.5% of patients taking 30-mg doses and 97.5% of patients taking 60-mg doses experienced an AE. Patients taking oxycodone were more likely to have euphoric mood, nausea, somnolence, vomiting, and dizziness, according to the researchers.