Naltrexone vs. Nefazodone for Treatment of Alcohol Dependence A Placebo-Controlled Trial

Kranzler, Henry R.; Modesto‐Lowe, Vania; Kirk, Jeffrey Van

doi:10.1016/s0893-133x(99)00135-9

Cited by 208 publications

(129 citation statements)

References 51 publications

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“…However, differences in trial design also limit the interpretation of findings. We also note that the presence of adverse effects early in treatment may affect treatment adherence and result in sampling bias that was not addressed in this study (Kranzler et al, 2000).…”

Section: Table 1 Baseline Demographics and Clinical Characteristics Omentioning

confidence: 97%

“…The specific procedures for the studies have been detailed in prior publications (Kranzler et al, 2000;Monterosso et al, 2001) and are briefly outlined here. Recruitment for the first study (study I) was conducted from January 1996 until January 1998 at the University of Pennsylvania (Monterosso et al, 2001).…”

Section: Study Samplementioning

confidence: 99%

“…A total of 240 subjects were randomly assigned to 24 weeks of naltrexone 100 mg/day or placebo and randomized to one of three different psychosocial interventions; cognitivebehavioral therapy (CBT), BRENDA, or simple medication management by a physician. The third study (study III), which involved 1 week of single-blind placebo treatment followed by 11 weeks of double-blind treatment, was conducted at the University of Connecticut Health Center between October 1993 and November 1996 (Kranzler et al, 2000). Subjects (n ¼ 183) were randomly assigned to receive naltrexone (50 mg/day), nefazodone (up to a maximum of 600 mg/day) or placebo in conjunction with CBT.…”

Section: Study Samplementioning

confidence: 99%

“…Although the majority of samples studied have shown a significant advantage of naltrexone over placebo (O'Malley et al, 1992;Volpicelli et al, 1992;Oslin et al, 1997;Chick et al, 2000;Anton et al, 2001;Monti et al, 2001;Morris et al, 2001), other studies have failed to show a significant drugplacebo difference (Kranzler et al, 2000;Krystal et al, 2001). Clearly, naltrexone does not help all alcohol-dependent adults and not all persons who drink alcohol show evidence of a 'high' (King et al, 1997) or an increase in endogenous opioids induced by alcohol consumption.…”

Section: Introductionmentioning

confidence: 99%

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A Functional Polymorphism of the μ-Opioid Receptor Gene is Associated with Naltrexone Response in Alcohol-Dependent Patients

Oslin

Berrettini

Kranzler

et al. 2003

Neuropsychopharmacol

552

399

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This study examined the association between two specific polymorphisms of the gene encoding the m-opioid receptor and treatment outcomes in alcohol-dependent patients who were prescribed naltrexone or placebo. A total of 82 patients (71 of European descent) who were randomized to naltrexone and 59 who were randomized to placebo (all of European descent) in one of three randomized, placebo-controlled clinical trials of naltrexone were genotyped at the A +118 G (Asn40Asp) and C +17 T (Ala6Val) SNPs in the gene encoding the m-opioid receptor (OPRM1). The association between genotype and drinking outcomes was measured over 12 weeks of treatment. In subjects of European descent, individuals with one or two copies of the Asp40 allele treated with naltrexone had significantly lower rates of relapse (p ¼ 0.044) and a longer time to return to heavy drinking (p ¼ 0.040) than those homozygous for the Asn40 allele. There were no differences in overall abstinence rates (p ¼ 0.611), nor were there differences in relapse rates or abstinence rates between the two genotype groups among those assigned to placebo. These preliminary results are consistent with prior literature demonstrating that the opioid system is involved in the reinforcing properties of alcohol and that allelic variation at OPRM1 is associated with differential response to a m-receptor antagonist. If replicated, these results would help to identify alcohol-dependent individuals who may be most likely to respond to treatment with naltrexone.

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Section: Table 1 Baseline Demographics and Clinical Characteristics Omentioning

confidence: 97%

Section: Study Samplementioning

confidence: 99%

Section: Study Samplementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A Functional Polymorphism of the μ-Opioid Receptor Gene is Associated with Naltrexone Response in Alcohol-Dependent Patients

Oslin

Berrettini

Kranzler

et al. 2003

Neuropsychopharmacol

552

399

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“…Consistent with these clinical findings, there have also been reports from preclinical studies in laboratory animals that describe naltrexone‐induced decreases in ethanol intake (Froehlich, Harts, Lumeng, & Li, 1987, 1990; Hubbell et al., 1986; Myers & Lankford, 1996; Parkes & Sinclair, 2000; Phillips, Wenger, & Dorow, 1997; Reid & Hunter, 1984), ethanol self‐administration (Heyser, Roberts, Schulteis, & Koob, 1999; Samson & Doyle, 1985; Sinden, Marfaing‐Jallat, & Le Magnen, 1983; Williams, Kane, & Woods, 2001), and the expression of ethanol‐induced conditioned place preference (Bechtholt & Cunningham, 2005; Cunningham, Henderson, & Bormann, 1998; Kuzmin, Sandin, Terenius, & Ogren, 2003; Middaugh & Bandy, 2000). Nevertheless, naltrexone is not always effective in humans (Gastpar et al., 2002; Kranzler, Modesto‐Lowe, & Van Kirk, 2000; Krystal, Cramer, Krol, Kirk, & Rosenheck, 2001). The reasons for such variability are not known, but may be related to the fact that naltrexone has non‐selective actions as an antagonist at all opioid receptors, and broad blockade of opioid receptors can trigger aversive and/or depressive‐like signs (West & Wise, 1988).…”

Section: Introductionmentioning

confidence: 99%

Kappa‐opioid receptors differentially regulate low and high levels of ethanol intake in female mice

et al. 2016

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IntroductionStudies in laboratory animals and humans indicate that endogenous opioids play an important role in regulating the rewarding value of various drugs, including ethanol (EtOH). Indeed, opioid antagonists are currently a front‐line treatment for alcoholism in humans. Although roles for mu‐ and delta‐opioid receptors have been characterized, the contribution of kappa‐opioid receptors (KORs) is less clear. There is evidence that changes in KOR system function can decrease or increase EtOH drinking, depending on test conditions. For example, female mice lacking preprodynorphin – the precursor to the endogenous KOR ligand dynorphin – have reduced EtOH intake. Considering that KORs can regulate dopamine (DA) transmission, we hypothesized that KORs expressed on DA neurons would play a prominent role in EtOH intake in females.MethodsWe used a Cre/loxP recombination strategy to ablate KORs throughout the body or specifically on dopamine uptake transporter (DAT)‐expressing neurons to investigate the role of KORs on preference for and intake of EtOH (2‐bottle choice), the transition from moderate to excessive EtOH drinking (intermittent EtOH access), and binge EtOH drinking (drinking in the dark [DID]).Results KOR deletion decreased preference for EtOH, although this effect was less pronounced when EtOH intake increased beyond relatively low levels.DiscussionOur findings indicate that KOR activation increases EtOH drinking via effects mediated, at least in part, by KORs on DA neurons. While the mechanisms of this regulation remain unknown, previous work suggests that alterations in negative reinforcement processes or sensitivity to the sensory properties of EtOH can affect preference and intake.

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Initial and Maintenance Naltrexone Treatment for Alcohol Dependence Using Primary Care vs Specialty Care

O’Malley¹,

Rounsaville²,

Farren³

et al. 2003

Arch Intern Med

126

101

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Naltrexone vs. Nefazodone for Treatment of Alcohol Dependence A Placebo-Controlled Trial

Cited by 208 publications

References 51 publications

A Functional Polymorphism of the μ-Opioid Receptor Gene is Associated with Naltrexone Response in Alcohol-Dependent Patients

A Functional Polymorphism of the μ-Opioid Receptor Gene is Associated with Naltrexone Response in Alcohol-Dependent Patients

Kappa‐opioid receptors differentially regulate low and high levels of ethanol intake in female mice

Initial and Maintenance Naltrexone Treatment for Alcohol Dependence Using Primary Care vs Specialty Care

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