The journal of pain : official journal of the American Pain Society
-
Randomized Controlled Trial Multicenter Study Comparative Study
Dose equivalence of immediate-release hydromorphone and once-daily osmotic-controlled extended-release hydromorphone: a randomized, double-blind trial incorporating a measure of assay sensitivity.
Dose selection of a once-daily, osmotic-controlled extended-release (ER) hydromorphone assumes that this drug and immediate-release (IR) hydromorphone are dose equivalent. This trial evaluated dose equivalence using a measure of assay sensitivity. Patients were converted to open-label IR hydromorphone, underwent dose titration, and those on a satisfactory dose entered a randomized, double-blind phase receiving 7 days of: 1) hydromorphone IR 5 times/day at approximately this dose; 2) once-daily hydromorphone ER at this dose; or 3) once-daily hydromorphone ER at one-half this dose. Efficacy was measured using breakthrough medication use, pain, sleep, and global assessments. Of 148 patients, 113 (76%) were randomized. IR and full-dose ER groups produced comparable effects on all measures. Although the prespecified primary analysis of the difference in total daily dose of breakthrough medication between the full-dose ER and half-dose ER groups was not significant, more patients in the half-dose ER group required an increase in breakthrough medication (P = .026) and the half-dose ER group both increased the number of breakthrough doses (P = .026) and had greater percent change in the total daily dose of breakthrough medication (P = .037) than the full-dose group, suggesting that switching from IR to ER hydromorphone at the same daily dose provides equivalent analgesia. ⋯ In a randomized, double-blind trial, the same total daily dose of immediate-release hydromorphone and once-daily osmotic-controlled extended-release hydromorphone had comparable effects. Detection of different effects between blinded dose levels was used as a measure of assay sensitivity. The measure of assay sensitivity can enhance the interpretation of dose equivalence or noninferiority trials.
-
Randomized Controlled Trial Comparative Study
Hyperalgesia in heroin dependent patients and the effects of opioid substitution therapy.
Evidence suggests that patients on opiate maintenance therapy for the treatment of addiction present with opioid-induced hyperalgesia. This study compared the experimental (cold-pressor, electrical stimulation) pain responses of 82 treatment-seeking heroin-dependent adults, randomized to methadone (METH, n = 11) or buprenorphine (BUP, n = 64) therapy, with matched drug free controls (n = 21). Heroin-dependent participants were evaluated at baseline (treatment entry), medication (METH or BUP) stabilization (4-8 weeks), and chronic administration (12-18 weeks), at trough (just prior to dosing) and peak (3 hours after dosing) plasma levels. Collection of the control group's pain responses occurred twice during a single session, 3 hours apart. Baseline comparisons indicate that heroin-dependent individuals demonstrate significantly shorter latencies to threshold and tolerance for cold-pressor pain than the control group. Across pain stimuli and time points, little change in pain responses was found over time, the exception being cold pressor pain tolerance, for which hyperalgesia significantly increased at trough METH/BUP levels in both groups as they stabilized in treatment. We conclude that heroin-dependent individuals are hyperalgesic, and that once stabilized in treatment, are not different in pain responses regardless of treatment agent. The effects of nonpharmacologic therapy and previous heroin use may explain increased hyperalgesia found with treatment. ⋯ To better understand the clinical phenomenon of opioid-induced hyperalgesia, this article describes experimental pain responses of heroin-dependent participants both prior to and over the course of maintenance therapy with methadone or buprenorphine. Hyperalgesia is present with illicit and treatment opioid use, and does not appear to appreciably improve over the course of treatment.