title: Effects of disulfiram on QTc interval in non-opioid-dependent and methadone-treated cocaine-dependent patients.
abstract: OBJECTIVE
  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.
authors: From the Department of Psychiatry and Behavioral Sciences, College of Medicine, University of Arkansas for Medical Sciences, Little Rock.
authors: Thomas S
authors: TS
authors: Atkinson
authors: Nichole
authors: N
authors: Sanders
authors: Michael
authors: M
authors: Mancino
authors: Alison
authors: A
authors: Oliveto
mesh_terms: D000328:Adult; D000427:Alcohol Deterrents / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000188:drug therapy*; D004221:Disulfiram / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage*; D008875:Middle Aged; D058850:Opiate Substitution Treatment; D009293:Opioid-Related Disorders / Q000188:drug therapy*
chemical_list: D000427:Alcohol Deterrents; D004221:Disulfiram; D008691:Methadone
references: AIDS Educ Prev. 1997 Jun;9(3):205-17
references: 9241388
references: Biol Psychiatry. 1995 Apr 15;37(8):560-3
references: 7619981
references: Life Sci (1962). 1964 Jul;3:763-7
references: 14203977
references: Drug Alcohol Depend. 2011 Jan 15;113(2-3):184-91
references: 20828943
references: J Palliat Med. 2010 Jan;13(1):33-8
references: 19824814
references: Arch Gen Psychiatry. 1976 Mar;33(3):391-3
references: 1259527
references: Am J Med Sci. 2002 Jul;324(1):37-44
references: 12120823
references: Am J Cardiol. 2006 Apr 15;97(8):1244-6
references: 16616034
references: J Addict Dis. 2010 Jan;29(1):15-22
references: 20390695
references: Heart. 2007 Sep;93(9):1051-5
references: 17344330
references: J Nerv Ment Dis. 1980 Jan;168(1):26-33
references: 7351540
references: J Cardiovasc Electrophysiol. 2012 May;23(5):527-33
references: 22136144
references: Eur Addict Res. 2005;11(1):44-9
references: 15608471
references: Neuropsychopharmacology. 2010 Nov;35(12):2440-9
references: 20736996
references: Adv Alcohol Subst Abuse. 1986 Winter;6(2):107-22
references: 3604786
references: J Clin Pharmacol. 1980 Aug-Sep;20(8-9):506-13
references: 7430415
references: Addiction. 2008 Dec;103(12):1987-93
references: 19469742
references: Drug Alcohol Depend. 2008 May 1;95(1-2):160-3
references: 18242882
references: Drug Alcohol Depend. 2007 Mar 16;87(2-3):202-9
references: 16979847
references: Addiction. 2000 Feb;95(2):219-28
references: 10723850
references: Expert Opin Emerg Drugs. 2006 Mar;11(1):91-8
references: 16503828
references: Biochem Pharmacol. 2008 Jan 1;75(1):34-56
references: 17880925
references: J Stud Alcohol. 1993 Mar;54(2):199-208
references: 8459714
references: Control Clin Trials. 1988 Dec;9(4):345-64
references: 3203525
references: Am J Cardiol. 2005 Apr 1;95(7):915-8
references: 15781034
references: Drug Alcohol Depend. 2011 Jan 15;113(2-3):88-95
references: 20828942
references: Addict Behav. 1998 Jul-Aug;23(4):449-61
references: 9698974
references: Psychol Addict Behav. 2004 Jun;18(2):180-3
references: 15238060
references: Can J Physiol Pharmacol. 1986 Jan;64(1):1-6
references: 2420426
references: Am Heart J. 2007 Jun;153(6):891-9
references: 17540188
references: Arch Gen Psychiatry. 2004 Mar;61(3):264-72
references: 14993114
references: Card Electrophysiol Rev. 2002 Sep;6(3):273-7
references: 12114851
references: J Subst Abuse Treat. 1991;8(4):203-12
references: 1787544
references: Pharmacotherapy. 2005 Nov;25(11):1523-9
references: 16232014
references: Drug Alcohol Depend. 1995 Jan;37(1):15-21
references: 7882869
references: Arch Gen Psychiatry. 1983 Aug;40(8):851-4
references: 6347118