Naltrexone and Coping Skills Therapy for Alcohol Dependence

O’Malley, Stephanie S.; Jaffe, Adam B.; Chang, Grace; Schottenfeld, Richard S.; Meyer, Roger E.; Rounsaville, Bruce J.

doi:10.1001/archpsyc.1992.01820110045007

Cited by 1,413 publications

(747 citation statements)

References 16 publications

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“…therapeutic efficacy of NTX in treating alcoholism (O'Malley et al, 1992(O'Malley et al, , 1996Volpicelli et al, 1992Volpicelli et al, , 1997Anton et al, 1999;Chick et al, 2000;Johnson and Ait-Daoud, 2000;Heinala et al, 2001;Krystal et al, 2001;Morris et al, 2001;Guardia et al, 2002), identifying factors that predict therapeutic response to NTX is a critical goal of alcoholism research. Although the cognitive effects of acute and chronic NTX may differ, recent data supports equivalent or greater efficacy of acute NTX dosing, relative to daily maintenance, in reducing excessive alcohol intake (Hernandez-Avila et al, 2006).…”

Section: Discussion Ntx Effects On Impulsive Choicementioning

confidence: 99%

Endogenous Opioid Blockade and Impulsive Responding in Alcoholics and Healthy Controls

Mitchell

Fields

et al. 2006

Neuropsychopharmacol

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The opioid receptor antagonist naltrexone (NTX) is one of few approved treatments for alcoholism, yet the mechanism by which it reduces drinking remains unclear. In rats, NTX reduces morphine-induced impulsive choice bias; however, nothing is known about the drug's effect on discrete aspects of impulsive behavior in humans, such as decision-making and inhibitory control. Here, we used a modified delay discounting procedure to investigate whether NTX improves decision-making or inhibitory control in humans. We measured the effect of acute NTX (50 mg) on choice between smaller sooner (SS) and larger later monetary rewards and on response errors (motor mismatch) in a high conflict condition in a group of abstinent alcoholics (AA) and healthy control subjects (CS). We previously reported that AA selected the SS option significantly more often than did CS in this paradigm. If the choice bias of AA is due to enhanced endogenous opioid signaling in response to potential reward, NTX should reduce such bias in the AA group. We found that NTX did not reliably reduce impulsive choice in the AA group; however, NTX's effect on choice bias across individuals was robustly predictable. NTX's effect on choice bias was significantly correlated with scores on Rotter's Locus of Control (LOC) scale; increasingly internal LOC scores predicted increasing likelihood of impulsive choices on NTX. In addition, we found that NTX significantly enhanced control of motor responses, particularly within the CS group. These results suggest that endogenous opioids may impair response selection during decision-making under conflict, and that NTX's effects on explicit decision-making are personality-dependent. Determining the biological basis of this dependence could have important implications for effective alcoholism treatment.

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Section: Discussion Ntx Effects On Impulsive Choicementioning

confidence: 99%

Endogenous Opioid Blockade and Impulsive Responding in Alcoholics and Healthy Controls

Mitchell

Fields

et al. 2006

Neuropsychopharmacol

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“…In the present study, dexamphetamine (the dextrorotatory isomer of amphetamine) was used at a dose of 30 mg (Metamina, Recip, six 5 mg tablets). The dose of NTX (ReVia, DuPont) was set at 50 mg, as this dose has proven to be efficacious in the treatment of the alcohol dependence syndrome (O'Malley et al, 1992;Volpicelli et al, 1992). Patients thus received either a 50 mg dose of NTX or identical placebo, followed by a 30 mg dose of dexamphetamine in a randomized design on 2 study days, 1 week apart.…”

Section: Methodsmentioning

confidence: 99%

Naltrexone Attenuates the Subjective Effects of Amphetamine in Patients with Amphetamine Dependence

Jayaram‐Lindström

Konstenius

Eksborg

et al. 2007

Neuropsychopharmacol

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Amphetamine abuse and dependence is a global health concern with a collateral increase in medical and social problems. Although some of the neurobiological mechanisms underlying amphetamine dependence and its devastating effects in humans are known, the development of rational and evidence-based treatment is lagging. There is evidence from preclinical studies suggesting that the endogenous opioid system plays a role in mediating some of the behavioral and neurochemical effects of amphetamine in a variety of controlled settings. In the present study we assessed the effects of naltrexone, an opioid antagonist (50 mg) on the subjective physiological and biochemical response to dexamphetamine (30 mg) in 20 amphetamine-dependent patients. Patients received naltrexone/amphetamine followed by placebo/amphetamine, 1 week apart in a randomized double-blind placebo-controlled design. The primary objective of the study was to evaluate the effect of pretreatment with naltrexone on the subjective response to amphetamine, using a Visual Analog Scale. The secondary objective was to investigate the effects of naltrexone on physiological and biochemical responses to amphetamine, as measured by changes in blood pressure, heart rate, skin conductance, and cortisol. Naltrexone significantly attenuated the subjective effects produced by dexamphetamine in dependent patients (po0.001). Pretreatment with naltrexone also significantly blocked the craving for dexamphetamine (po0.001). There was no difference between the groups on the physiological measures. The results suggest that the subjective effects of amphetamine could be modulated via the endogenous opioid system. The potential of naltrexone as an adjunct pharmaceutical for amphetamine dependence is promising.

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“…The earliest randomized controlled trials (RCTs) of naltrexone generated important evidence as to potential treatment mechanisms (O'Malley et al , 1992; Volpicelli et al , 1992; reviewed in Pettinati et al , 2006). In the seminal trial naltrexone reduced the incidence of relapse to heavy drinking, quantity of consumption and weekly reports of craving, but not the likelihood of an initial lapse (Volpicelli et al , 1992).…”

Section: Introductionmentioning

confidence: 99%

Effects of naltrexone on alcohol self‐administration and craving: meta‐analysis of human laboratory studies

et al. 2016

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Randomized clinical trials have established the efficacy of naltrexone for reducing quantity of alcohol consumption and incidence of relapse to heavy drinking. To evaluate putative treatment mechanisms, human laboratory studies have examined naltrexone's effects on alcohol responses and self‐administration during short‐term medication protocols. Results from these studies are inconsistent and have yet to be examined in aggregate. This meta‐analysis aimed to quantify naltrexone's effects on alcohol self‐administration and craving in the context of placebo‐controlled human laboratory trials. Potential moderators of medication effects were also examined. Meta‐analyses of alcohol self‐administration (k = 9, N = 490) and craving (k = 16, N = 748) confirmed that, under controlled experimental conditions, naltrexone reduces the quantity of consumption (Hedges' g = −.277, SE = .074, 95 percent CI = −.421, −.133, p < .001) and magnitude of self‐reported craving (g = −.286, SE = .066, 95 percent CI = −.416, −.156, p < .001) relative to placebo. Subgroup and moderation analyses found no evidence that effect sizes differed by study population (dependent versus non‐dependent drinkers), laboratory paradigm or duration of medication exposure. These results substantiate prior evidence for reductions in event‐level craving and consumption as potential treatment mediators, also establishing effect sizes to inform future human laboratory trials. From a clinical perspective, these results may provide additional evidence regarding naltrexone's efficacy in the context of acute or subacute dosing regimens.

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Naltrexone and Coping Skills Therapy for Alcohol Dependence

Cited by 1,413 publications

References 16 publications

Endogenous Opioid Blockade and Impulsive Responding in Alcoholics and Healthy Controls

Endogenous Opioid Blockade and Impulsive Responding in Alcoholics and Healthy Controls

Naltrexone Attenuates the Subjective Effects of Amphetamine in Patients with Amphetamine Dependence

Effects of naltrexone on alcohol self‐administration and craving: meta‐analysis of human laboratory studies

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