From the Department of Psychiatry and Behavioral Sciences, College of Medicine, University of Arkansas for Medical Sciences, Little Rock.
J Addict Med. 2013 Jul-Aug;7(4):243-8. doi: 10.1097/ADM.0b013e3182928e02.
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.
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.
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.
These results suggest that cocaine use and possibly MT status, but not disulfiram, are risk factors for QTc prolongation.
已知美沙酮和可卡因均会延长 QTc 间期，这是导致潜在致命性心律失常的一个危险因素。双硫仑常用于美沙酮维持治疗，以促进戒酒，已被证明对可卡因依赖有一定疗效。双硫仑对可卡因和美沙酮的代谢有不同的影响，但它对美沙酮或可卡因引起的 QTc 间期变化的影响尚不清楚。因此，在参加一项为期 14 周、随机、双盲、安慰剂对照的双硫仑临床研究的可卡因依赖患者亚组中，前瞻性地确定了双硫仑对 QTc 间期的影响。
阿片类药物依赖的参与者被诱导进入美沙酮（第 1-2 周；MT），而 MT 和非阿片类药物依赖（UT）的参与者被随机分配在以下剂量之一接受双硫仑（第 3-14 周）：0、250、375 或 500mg/d。在研究入组前和第 2 周和第 4 周进行心电图检查。
对 23 名 MT 和 18 名 UT 参与者的完整 QTc 间期数据进行了分析。无论双硫仑剂量和时间点如何，MT 参与者的 QTc 间期往往高于 UT 参与者，但双硫仑并未使 QTc 间期产生差异变化。然而，最近可卡因使用者的 QTc 间期明显大于没有最近可卡因使用者。
这些结果表明，可卡因使用和可能的美沙酮状态，而不是双硫仑，是 QTc 延长的危险因素。
