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 were prospectively determined.

Methods: Opioid-dependent participants were inducted onto methadone (weeks 1-2; MT) and both MT and non-opioid-dependent (UT) participants were randomized to receive disulfiram (weeks 3-14) at one of the following doses: 0, 250, 375, or 500 mg/d. Electrocardio-grams were obtained before 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 participants relative to UT 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 in 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.

Figure 1

The impact of MT status (top panel) as well as recent cocaine use (bottom panel) on QTc interval: MT (closed circles), UT (open circles); recent cocaine use (COC+, closed circles) and no recent cocaine use (COC-, open circles). Each point represents the mean +/- SD.

Figure 2

The impact of disulfiram dose (0, 250, 375, 500 mg/day) and recent cocaine use on QTc interval: Cocaine-negative urines (COC-, gray bars), cocaine-positive urines (COC+, black bars). Each bar represents the mean +/- SD.