Effects of Disulfiram on QTc Interval in Non–Opioid-Dependent and Methadone-Treated Cocaine-Dependent Patients

Abstract

Objectives Methadone and cocaine are each known to prolong the QTc interval, a risk factor for developing potentially fatal cardiac arrhythmias. Disulfiram, often administered in the context of methadone maintenance to facilitate alcohol abstinence, has been shown to have some efficacy for cocaine dependence. Disulfiram has differential effects on cocaine and methadone metabolism, but its impact on methadone- or cocaine-induced changes in QTc interval is unclear. Thus, the effects of disulfiram on QTc interval in a subset of cocaine dependent patients participating in a 14 week, randomized, double blind, placebo-controlled clinical trial of disulfiram was prospectively determined. Methods Opioid dependent participants were inducted onto methadone (wks 1-2; MT) and both MT and nonopioid dependent (UT) participants were randomized to receive disulfiram (wks 3-14) at one of the following doses: 0, 250, 375, or 500 mg/day. Electrocardiograms (ECGs) were obtained prior to study entry and during weeks 2 and 4. Results Complete QTc interval data in 23 MT and 18 UT participants were analyzed. QTc interval tended to be higher in MT relative to UT dependent participants, regardless of disulfiram dose and time point, but disulfiram did not differentially alter QTc interval. QTc interval was, however, significantly greater in participants with recent cocaine use than those with no recent use. Conclusions These results suggest that cocaine use and possibly MT status, but not disulfiram, are risk factors for QTc prolongation.

Alcohol Use Disorders in Opioid Maintenance Therapy: Prevalence, Clinical Correlates and Treatment

“…Disulfiram was also studied as a possible medication for the treatment of cocaine dependence in methadone-stabilized patients [117] and positive results were reported in patients maintained with buprenorphine [118], but disulfiram may also work in those with current alcohol use disorder [107]. Unlike cocaine and possibly methadone, disulfiram was not found to prolong the QTc interval [119]. …”

Electrocardiographic characteristics in individuals with cocaine use disorder

“…Prolonged QTc interval also contributes to cardiac complications such as torsade de pointes , ventricular tachycardia, and cardiac arrest . Specifically, QTc interval is significantly greater in participants with recent cocaine use; however, cocaine‐associated QTc prolongation returns to baseline during the first week of cocaine abstinence …”