A double-blind, placebo-controlled trial of amantadine, propranolol, and their combination for the treatment of cocaine dependence in patients with severe cocaine withdrawal symptoms

Kampman, Kyle M.; Dackis, Charles A.; Lynch, Kevin G.; Pettinati, Helen M.; Tirado, Carlos; Gariti, Peter; Sparkman, Thorne; Atzram, Michal; O’Brien, Charles P.

doi:10.1016/j.drugalcdep.2006.04.002

Cited by 80 publications

(67 citation statements)

References 35 publications

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“…Stress and cue-related increases in heart rate and blood pressure have been observed alongside increases in cocaine craving within recently abstinent cocaine abusers in several studies (Back et al, 2005;Sinha et al, 2001Sinha et al, , 2003Fox et al, 2005Fox et al, , 2006. b-Adrenergic blockade by drugs such as propranolol have also been shown to reduce the symptoms of autonomic arousal associated with early cocaine abstinence and improve treatment outcome (Kampman et al, 2001b(Kampman et al, , 2006. It may therefore be the case that increased heart rate and blood pressure represent a non-specific physiological marker of stress-and cue-induced craving state that may be elevated during cocaine abstinence.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Sensitivity to Stress and Drug/Alcohol Craving in Abstinent Cocaine-Dependent Individuals Compared to Social Drinkers

Fox

Hong

Siedlarz

et al. 2007

Neuropsychopharmacol

165

164

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Chronic exposure to cocaine is associated with neuroadaptions in stress and reward circuits that may increase susceptibility to relapse. We examined whether there are alterations in stress response and craving in abstinent cocaine-dependent individuals compared with a demographically matched group of non-addicted socially drinking community controls. Forty treatment-engaged abstinent cocaine patients (17F/23M) and 40 controls (19F/21M) were exposed to a brief 5 min guided imagery of individually calibrated stressful situations, personal drug/alcohol-related situation and a neutral-relaxing situation, one imagery per session, presented in random order. Craving, anxiety, emotion rating scales, and physiological measures were assessed. Cocaine patients reported significantly higher and more persistent stress-and cue-induced drug/alcohol craving, negative emotions, and physiological responses compared with social drinkers. In cocaine patients, stress-and cue-induced drug craving was accompanied by increased anger, fear, sadness, heart rate, and SBP. Controls reported minimal stress-induced craving and only increases in anxiety and SBP during stress exposure. Cue-induced alcohol craving was accompanied only by an increase in relaxed state. Females reported increased stress-induced anxiety and sadness compared with males, while males were emotionally and physiologically more reactive in the cue condition. These findings are the first to document functional alterations in stress-and reward-related affect and physiology in recently abstinent cocaine patients that is marked by an enhanced sensitivity to stress-and drug-related cue exposure. These data suggest that recovery from chronic cocaine abuse could be hampered by a hyper-responsive stress-and drug-craving state that increases cocaine relapse susceptibility.

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Section: Discussionmentioning

confidence: 99%

Enhanced Sensitivity to Stress and Drug/Alcohol Craving in Abstinent Cocaine-Dependent Individuals Compared to Social Drinkers

Fox

Hong

Siedlarz

et al. 2007

Neuropsychopharmacol

165

164

View full text Add to dashboard Cite

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“…Baseline number of cocaine-positive urine drug tests as well as scores on the Cocaine Selective Severity Assessment predict treatment outcome (Kampman et al, 2002;Ahmadi et al, 2006). The influence of drug use severity on medication efficacy in the present review is exemplified when evaluating the discordant results for amantadine (e.g., Shoptaw et al, 2002;Kampman et al, 2006). Shoptaw and colleagues demonstrated the efficacy of amantadine (200 mg/day) for reducing cocaine use; however, this was not observed with prospectively enrolled subjects with high scores on the Cocaine Selective Severity Assessment, in whom a higher dose was used (300 mg/day; Kampman et al, 2006).…”

Section: Behavioral Phenotypes As Predictors Of Clinical Efficacymentioning

confidence: 91%

“…The influence of drug use severity on medication efficacy in the present review is exemplified when evaluating the discordant results for amantadine (e.g., Shoptaw et al, 2002;Kampman et al, 2006). Shoptaw and colleagues demonstrated the efficacy of amantadine (200 mg/day) for reducing cocaine use; however, this was not observed with prospectively enrolled subjects with high scores on the Cocaine Selective Severity Assessment, in whom a higher dose was used (300 mg/day; Kampman et al, 2006). This indicates that drug use severity must be considered when selecting enrollment criteria.…”

Section: Behavioral Phenotypes As Predictors Of Clinical Efficacymentioning

confidence: 98%

Evaluation of the “Pipeline” for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research

2016

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“…In recent years, there have been a series of double blind, placebo-controlled clinical trials of combination medications for treating primarily alcohol or drug dependence in patients without concomitant psychiatric disorders (see, e.g., Ait-Daoud, Johnson, Prihoda, & Hargita, 2001;Anton, O'Malley, Ciraulo, Cisler et al, 2006;Kampman, Dackis, Lynch, Pettinati et al, 2006;Kiefer & Wiedemann, 2004), including adding disulfiram to naltrexone (Petrakis, Poling, Levinson, Nich et al, 2005), or to acamprosate -another FDA-approved medication for treating alcohol dependence (Besson, Aeby, Kasas, Lehert et al, 1998). The treatment strategy tested in the present study was combining two medications (added to twice weekly sessions of cognitive behavioral therapy) to treat patients presenting with dual cocaine and alcohol dependence.…”

Section: Introductionmentioning

confidence: 99%

A double blind, placebo-controlled trial that combines disulfiram and naltrexone for treating co-occurring cocaine and alcohol dependence

Pettinati

Kampman

Lynch

et al. 2008

Addictive Behaviors

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BACKGROUND-This is a double blind, placebo-controlled trial that evaluated the efficacy of disulfiram, naltrexone and their combination in patients with co-occurring cocaine and alcohol dependence.METHODS-208 patients were randomized to disulfiram (250mg/day), naltrexone (100mg/day), the combination, or placebo for 11 weeks. Outcomes were in-trial abstinence from cocaine and/or alcohol.RESULTS-Few safety concerns were reported, although medication adherence was low in a number of patients for both medications, alone or in combination. In the primary analyses (GEE modeling), abstinence from cocaine as measured by cocaine-negative urines and days of self-reported abstinence from cocaine or alcohol did not differ between placebo and any of the medication groups. However, patients taking disulfiram (alone or in combination) were most likely to achieve combined abstinence from cocaine and alcohol. Secondary analyses revealed that patients taking the disulfiramnaltrexone combination were most likely to achieve 3 consecutive weeks of abstinence from cocaine and alcohol.CONCLUSION-There was an association between disulfiram treatment and abstinence from cocaine and alcohol. More patients taking the disulfiram-naltrexone combination achieved 3 consecutive weeks of abstinence in treatment than placebo-treated patients.

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A double-blind, placebo-controlled trial of amantadine, propranolol, and their combination for the treatment of cocaine dependence in patients with severe cocaine withdrawal symptoms

Cited by 80 publications

References 35 publications

Enhanced Sensitivity to Stress and Drug/Alcohol Craving in Abstinent Cocaine-Dependent Individuals Compared to Social Drinkers

Enhanced Sensitivity to Stress and Drug/Alcohol Craving in Abstinent Cocaine-Dependent Individuals Compared to Social Drinkers

Evaluation of the “Pipeline” for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research

A double blind, placebo-controlled trial that combines disulfiram and naltrexone for treating co-occurring cocaine and alcohol dependence

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