Background
Cocaine dependence is a substantial public health problem, yet there are no clearly
effective medication treatments. Amphetamine and topiramate have both shown promise
for the treatment of cocaine dependence in preclinical and early-stage clinical studies.
Methods
Eighty-one cocaine-dependent adults were randomized to receive a combination of extended-release
mixed amphetamine salts (MAS-ER) and topiramate or placebo for 12 weeks under double-blind
conditions. MAS-ER doses were titrated over 2 weeks to a maximum dose of 60 mg daily,
and topiramate doses were titrated over 6 weeks to a maximum dose of 150 mg twice
daily. All participants received a supportive behavioral intervention. The primary
outcome was the proportion of individuals who achieved 3 consecutive weeks of abstinence
as measured by urine toxicology confirmed self-report.
Results
The overall proportion of participants who achieved 3 consecutive weeks of abstinence
was larger in the extended-release mixed amphetamine salts and topiramate group (33.3%)
than in placebo group (16.7%). There was a significant moderating effect of baseline
total number of cocaine use days (Wald χ2 = 3.75, df = 1, p = .05) on outcome, suggesting that the combination treatment was most effective for
participants with a high baseline frequency of cocaine use.
Conclusions
The results of this study supported our hypothesis that the combination of MAS-ER
and topiramate would be superior to placebo in achieving 3 weeks of consecutive abstinence.
These findings provide evidence that the combination of MAS-ER and topiramate is efficacious
in promoting abstinence in cocaine-dependent individuals.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Results from the 2010 National Survey on Drug Use and Health: Summary of national findings.Office of Applied Studies, Rockville, MD2011
- Prevalence, correlates, disability, and comorbidity of DSM-IV drug abuse and dependence in the United States: Results from the national epidemiologic survey on alcohol and related conditions.Arch Gen Psychiatry. 2007; 64: 566-576
- A meta-analytic review of psychosocial interventions for substance use disorders.Am J Psychiatry. 2008; 165: 179-187
- Pharmacological treatment of cocaine dependence: A systematic review.Addiction. 2002; 97: 931-949
- Cocaine Rapid Efficacy Screening Trial (CREST): A paradigm for the controlled evaluation of candidate medications for cocaine dependence.Addiction. 2005; 100: 1-11
- New treatments for cocaine dependence: A focused review.Int J Neuropsychopharmacol. 2008; 11: 425-438
- Neuroadaptations involved in amphetamine and cocaine addiction.Drug Alcohol Depend. 1998; 51: 141-153
- An overview of systematic reviews of the effectiveness of opiate maintenance therapies: Available evidence to inform clinical practice and research.J Subst Abuse Treat. 2005; 28: 321-329
- Pharmacotherapy and pharmacogenetics of nicotine dependence.Am J Psychiatry. 2005; 162: 1441-1451
- Imaging dopamine transmission in cocaine dependence: Link between neurochemistry and response to treatment.Am J Psychiatry. 2011; 168: 634-641
- Double-blind placebo-controlled trial of methylphenidate in the treatment of adult ADHD patients with comorbid cocaine dependence.Exp Clin Psychopharmacol. 2002; 10: 286-294
- Treatment of cocaine dependent treatment seekers with adult ADHD: Double-blind comparison of methylphenidate and placebo.Drug Alcohol Depend. 2006; 87: 20-29
- Replacement medication for cocaine dependence: Methylphenidate.J Clin Psychopharmacol. 1997; 17: 485-488
- Dextroamphetamine for cocaine-dependence treatment: A double-blind randomized clinical trial.J Clin Psychopharmacol. 2001; 21: 522-526
- Pilot randomized double blind placebo-controlled study of dexamphetamine for cocaine dependence.Addiction. 2003; 98: 1137-1141
- A double-blind, placebo-controlled trial of modafinil for cocaine dependence.Neuropsychopharmacology. 2005; 30: 205-211
- Six-month trial of bupropion with contingency management for cocaine dependence in a methadone-maintained population.Arch Gen Psychiatry. 2006; 63: 219-228
- Modafinil for the treatment of cocaine dependence.Drug Alcohol Depend. 2009; 104: 133-139
- Effects of oral methamphetamine on cocaine use: A randomized, double-blind, placebo-controlled trial.Drug Alcohol Depend. 2009; 101: 34-41
- Efficacy of psychostimulant drugs for cocaine dependence.Cochrane Database Syst Rev. 2010; 2010 (CD007380)
- The effect of individual cocaine withdrawal symptoms on outcomes in cocaine users.Addict Behav. 2005; 30: 1125-1134
- Anticonvulsant drugs in cocaine dependence: A systematic review and meta-analysis.J Subst Abuse Treat. 2010; 38: 66-73
- A pilot trial of topiramate for the treatment of cocaine dependence.Drug Alcohol Depend. 2004; 75: 233-240
- Randomized, double-blind, placebo-controlled trial of vigabatrin for the treatment of cocaine dependence in Mexican parolees.Am J Psychiatry. 2009; 166: 1269-1277
- Topiramate modulates GABA-evoked currents in murine cortical neurons by a nonbenzodiazepine mechanism.Epilepsia. 2000; 41: S17-S20
- Topiramate blocks kainate-evoked cobalt influx into cultured neurons.Epilepsia. 2000; 41: S45-S47
- Oral topiramate for treatment of alcohol dependence: A randomised controlled trial.Lancet. 2003; 361: 1677-1685
- Topiramate for treating alcohol dependence: A randomized controlled trial.JAMA. 2007; 298: 1641-1651
- Use of oral topiramate to promote smoking abstinence among alcohol-dependent smokers: A randomized controlled trial.Arch Intern Med. 2005; 165: 1600-1605
- Safety and efficacy of GABAergic medications for treating alcoholism.Alcohol Clin Exp Res. 2005; 29: 248-254
- Development of novel pharmacotherapies for the treatment of alcohol dependence: Focus on antiepileptics.Alcohol Clin Exp Res. 2004; 28: 295-301
- Topiramate selectively attenuates nicotine-induced increases in monoamine release.Synapse. 2001; 42: 196-198
- Principles of Therapeutics.in: 10th ed. Goodman and Gilman's the pharmacological basis of therapeutics. 54. McGraw-Hill, New York2001
- One-year follow-up of psychotherapy and pharmacotherapy for cocaine dependence.Arch Gen Psychiatry. 1994; 51: 989-997
- Diagnostic and Statistical Manual of Mental Disorders.4th ed., text revision. American Psychiatric Association, Washington, DC2000
- Compliance Enhancement: A Manual for the Psychopharmacology of Drug Abuse and Dependence (Yale University Psychotherapy Development Center Training Series No. 4).Yale University Psychotherapy Development Center, West Haven, CT1999
- Structured Clinical Interview for DSM-IV Axis I Disorders—Patient Edition (SCID-I/P, Version 2.0).Biometrics Research Department, New York State Psychiatric Institute, New York1995
- Measuring Alcohol Consumption: Psychosocial and Biochemical Methods.in: The Humana Press, Totowa, NJ1992: 41-72
- A double-blind, placebo-controlled trial of tiagabine for the treatment of cocaine dependence.Drug Alcohol Depend. 2007; 91: 141-148
- SAS version 9.2..Cary, NC, SAS Institute2009
- Antidepressant drug effects and depression severity: A patient-level meta-analysis.JAMA. 2010; 303: 47-53
- Utility of lead-in period in cocaine dependence pharmacotherapy trials.Drug Alcohol Depend. 2005; 77: 7-11
- Cocaine withdrawal severity and urine toxicology results from treatment entry predict outcome in medication trials for cocaine dependence.Addict Behav. 2002; 27: 251-260
- Effects of acute topiramate dosing on methamphetamine-induced subjective mood.Int J Neuropsychopharmacol. 2007; 10: 85-98
- Combined pharmacotherapies and behavioral interventions for alcohol dependence: The COMBINE study: A randomized controlled trial.JAMA. 2006; 295: 2003-2017
Article info
Publication history
Published online: July 16, 2012
Accepted:
May 26,
2012
Received in revised form:
May 24,
2012
Received:
February 25,
2012
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.