The presence or absence of QTc prolongation in buprenorphine-naloxone among youth with opioid dependence.
This study aimed to evaluate buprenorphine-naloxone’s effects on the QTc in youth with opioid dependence (the QTc, or “corrected QT interval,” is a measure of the duration of electrical activation and recovery of the ventricular muscle). Prolongation of the QTc increases the risk for torsades de pointes (TdP), an uncommon variant of polymorphic ventricular tachycardia, that can result in syncope, ventricular fibrillation, and sudden death. Buprenorphine is a partial agonist that is an effective treatment for opioid dependence. Compared with methadone, it has a lower risk of QTc prolongation in adults, and may also reduce the risk of TdP, but it is less studied in youth. This study involved a secondary analysis of the electrocardiogram data from 95 individuals who participated in a multi-site trial for youth with opioid dependence (CTN-0010). The participants were randomized to a 2-week (DETOX) or a 12-week course of buprenorphine-naloxone (BUP). At baseline, 12-lead electrocardiograms were done at weeks 4 and 12, and QTc intervals were hand-measured and calculated using Bazett formula. Increases above 60 milliseconds were considered clinically significant, and readings above 450 milliseconds (in men) and 470 milliseconds (in women) indicated a prolonged QTc.
Results found that mean QTc intervals were higher for BUP than for DETOX participants at baseline, week 4, and week 12 (p=0.045), and women had longer mean QTc intervals than men (p<0.0005). Variations in the QTc intervals were observed in some; however, none were above 500 milliseconds — the level at which risk for TdP becomes more significant. The few QTc prolongations that occurred were among participants who were receiving psychotropic medications that are known to prolong the QTc, and indicate a need for further evaluation of potential interactions between buprenorphine-naloxone and SSRIs, or other commonly used psychotropic medications.
Conclusions: In this randomized trial, the mean QTc at baseline, before randomization, was higher in BUP than in DETOX patients. Minimal changes in the QTc were seen at 4 and 12 weeks in a few patients in both groups. There was no evidence that buprenorphine-naloxone alone increased the QTc to a level that increased the risk for TdP. These results add to the known safety data on buprenorphine-naloxone among adults, and could add to the literature that buprenorphine-naloxone is a safe and effective treatment for opioid-dependent young adults with clinically significant QTc prolongations, or who are at risk for developing it.
Related protocols: CTN-0010