Biomedical subjects

Barbara J Mason

Publications and source records attributed to Barbara J Mason.

12 recordsLinked to original sources

PubMed2006

Combined pharmacotherapies and behavioral interventions for alcohol dependence: the COMBINE study: a randomized controlled trial.

CONTEXT: Alcohol dependence treatment may include medications, behavioral therapies, or both. It is unknown how combining these treatments may impact their effectiveness, especially in the context of primary care and other nonspecialty settings. OBJECTIVES: To evaluate the efficacy of medication, behavioral therapies, and their combinations for treatment of alcohol dependence and to evaluate placebo effect on overall outcome. DESIGN, SETTING, AND PARTICIPANTS: Randomized controlled trial conducted January 2001-January 2004 among 1383 recently alcohol-abstinent volunteers (median age, 44 years) from 11 US academic sites with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, diagnoses of primary alcohol dependence. INTERVENTIONS: Eight groups of patients received medical management with 16 weeks of naltrexone (100 mg/d) or acamprosate (3 g/d), both, and/or both placebos, with or without a combined behavioral intervention (CBI). A ninth group received CBI only (no pills). Patients were also evaluated for up to 1 year after treatment. MAIN OUTCOME MEASURES: Percent days abstinent from alcohol and time to first heavy drinking day. RESULTS: All groups showed substantial reduction in drinking. During treatment, patients receiving naltrexone plus medical management (n = 302), CBI plus medical management and placebos (n = 305), or both naltrexone and CBI plus medical management (n = 309) had higher percent days abstinent (80.6, 79.2, and 77.1, respectively) than the 75.1 in those receiving placebos and medical management only (n = 305), a significant naltrexone x behavioral intervention interaction (P = .009). Naltrexone also reduced risk of a heavy drinking day (hazard ratio, 0.72; 97.5% CI, 0.53-0.98; P = .02) over time, most evident in those receiving medical management but not CBI. Acamprosate showed no significant effect on drinking vs placebo, either by itself or with any combination of naltrexone, CBI, or both. During treatment, those receiving CBI without pills or medical management (n = 157) had lower percent days abstinent (66.6) than those receiving placebo plus medical management alone (n = 153) or placebo plus medical management and CBI (n = 156) (73.8 and 79.8, respectively; P<.001). One year after treatment, these between-group effects were similar but no longer significant. CONCLUSIONS: Patients receiving medical management with naltrexone, CBI, or both fared better on drinking outcomes, whereas acamprosate showed no evidence of efficacy, with or without CBI. No combination produced better efficacy than naltrexone or CBI alone in the presence of medical management. Placebo pills and meeting with a health care professional had a positive effect above that of CBI during treatment. Naltrexone with medical management could be delivered in health care settings, thus serving alcohol-dependent patients who might otherwise not receive treatment. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00006206.

Acamprosate↗

PubMed2006

Effect of oral acamprosate on abstinence in patients with alcohol dependence in a double-blind, placebo-controlled trial: the role of patient motivation.

This is the first US study to evaluate the clinical efficacy of acamprosate (Campral), a newly FDA-approved medication for maintaining abstinence in patients with alcohol dependence following alcohol withdrawal. We compared effects of the standard 2 g dose (n=258) and an exploratory 3 g dose of acamprosate (n=83) versus placebo (n=260), and evaluated drug safety in a double-blind, placebo-controlled 6-month trial conducted in 21 outpatient clinics across the US. Participants were 601 volunteers with current alcohol dependence recruited primarily by advertisement. All patients concomitantly received eight sessions of brief manual-guided counseling (www.alcoholfree.info). The main outcome measure was the percentage of alcohol-free days over the 6-month study. Self-report was validated by breath alcohol concentration, gamma-glutamyltransferase (GGT) and collateral informant interviews. The percentage of abstinent days did not differ significantly across groups in a priori analysis (54.3% for placebo, 56.1% for 2 g, 60.7% for 3 g). Post-hoc analysis controlling for baseline variables and treatment exposure found acamprosate was associated with a significantly higher percentage of abstinent days than placebo (52.3% for placebo, 58.2% for 2 g, 62.7% for 3 g; P=0.01), with an even greater effect in the subgroup of 241 patients having a baseline goal of abstinence (58.1% for placebo, 70.0% for 2 g, 72.5% for 3 g; P=0.02). There were no deaths or serious drug-related adverse events. The US study findings suggest that acamprosate is safe and well tolerated in a broadly inclusive sample of alcoholics and appears effective in populations of patients motivated to have a treatment goal of abstinence.

Acamprosate↗

PubMed2006

Sertraline treatment of co-occurring alcohol dependence and major depression.

BACKGROUND: Major depressive disorder occurs commonly in association with alcohol dependence, both in clinical samples and in the community. Efforts to treat major depressive disorder in alcoholics with antidepressants have yielded mixed results. This multicenter, double-blind, placebo-controlled trial of sertraline was designed to address many of the potential methodological shortcomings of studies of co-occurring disorders. METHOD: Following a 1-week, single-blind, placebo lead-in period, 328 patients with co-occurring major depressive disorder and alcohol dependence were randomly assigned to receive 10 weeks of treatment with sertraline (at a maximum dose of 200 mg/d) or matching placebo. Randomization was stratified, based on whether initially elevated scores on the 17-item Hamilton Depression Rating Scale declined with cessation of heavy drinking, resulting in a sample of 189 patients with Hamilton Depression Rating Scale scores > or =17 (group A) and 139 patients with Hamilton Depression Rating Scale scores < or =16 (group B). RESULTS: Both depressive symptoms and alcohol consumption decreased substantially over time in both groups. There were no reliable medication group differences on depressive symptoms or drinking behavior in either group A or B patients. CONCLUSION: Despite careful attention to methodological considerations, this study does not provide consistent support for the use of sertraline to treat co-occurring major depressive disorder and alcohol dependence. The high rate of response among placebo-treated patients may help to explain these findings. Further research is needed to identify efficacious treatments for patients with these commonly co-occurring disorders.

Adult↗

PubMed2006

Understanding and treating alcohol dependence.

This article represents the proceedings of a symposium presented at the 158th Annual Meeting of the American Psychiatric Association held in Atlanta, Georgia, on May 24, 2005. The organizer/chairman was Bankole A. Johnson, DSc, MD, PhD. The presentations included the following: (1) Neuropharmacological Basis of Alcohol Dependence, by George F. Koob, PhD; (2) Recent Developments in the Genetics of Alcohol Dependence, by Marc A. Schuckit, MD; (3) New Pharmacological Strategies for Treating Alcohol Dependence, by Barbara J. Mason, PhD; (4) New Medications: The Use of Anticonvulsants, Both Alone and in Combination, with Various Forms of Psychotherapy, by Bankole A. Johnson, DSc, MD, PhD; and (5) Differential Effects of Pharmacological Agents on Craving, by Nassima Ait-Daoud, MD.

Alcoholism↗

PubMed2005

Acamprosate in the treatment of alcohol dependence.

Acamprosate is indicated for the maintenance of abstinence from alcohol in patients with alcohol dependence who are abstinent at treatment initiation in combination with psychosocial support. Acamprosate is a synthetic taurine analogue that seems to act centrally to restore the normal activity of glutamatergic neurotransmission altered by chronic alcohol exposure. Over the past 15 years, the safety and efficacy of acamprosate for alcohol dependence have been well established in multiple double-blind, placebo-controlled trials. Overall, acamprosate has been consistently associated with greater beneficial effects on measures of alcohol abstinence compared with placebo. Specifically, patients treated with acamprosate achieve greater rates of complete abstinence, longer times to first drink and/or increased duration of cumulative abstinence when compared with placebo. Acamprosate received approval by the US FDA for the treatment of alcohol dependence in July 2004 and is currently prescribed in 28 countries.

Acamprosate↗

PubMed2005

Rationale for combining acamprosate and naltrexone for treating alcohol dependence.

OBJECTIVE: This article provides an evidence-based review of acamprosate and naltrexone, used alone and in combination. Both medications are gaining increasing availability worldwide by prescription for the treatment of alcohol dependence. There is scientific and clinical interest in examining these drugs in combination, given their high tolerability, moderate effect sizes, different pharmacological profiles and potentially different effects on drinking outcomes. METHOD: This article includes a review of the key similarities and differences between acamprosate and naltrexone in the treatment of alcohol dependence; the published double-blind, placebo-controlled trials of acamprosate and naltrexone across a uniform range of outcome criteria to elucidate the differences and similarities in the behavioral effects of these drugs; the two published pharmacokinetic and pharmacodynamic drug interaction studies of acamprosate and naltrexone; and the single-site clinical trial of acamprosate and naltrexone used alone and in combination relative to placebo. RESULTS: Pharmacokinetic and pharmacodynamic studies report an increase in acamprosate plasma levels with no clinically significant elevation in adverse events when the two drugs are used in combination. Data from dose-response studies for acamprosate alone suggest that the augmentation of acamprosate plasma levels by co-administration of naltrexone may have clinical benefits. CONCLUSIONS: These factors support investigating the efficacy and safety of combining acamprosate and naltrexone for the treatment of alcohol dependence in a large-scale multisite trial, with evaluation of potential predictors of response to each drug alone and in combination relative to placebo.

Acamprosate↗

PubMed2005

How pilot studies improve large-scale clinical trials: lessons learned from the COMBINE Study.

OBJECTIVE: The design of a clinical trial to evaluate a potential therapy requires decisions about issues that include safety, efficacy, measurement, feasibility and training. Experience from the COMBINE Study, which tests the combination of medications and behavioral therapies for alcohol dependence, is presented as an example of how pilot studies improve large-scale clinical trials. METHOD: The COMBINE Pilot 1 inpatient study was designed to inform the main trial about the safety and tolerability of the doses of acamprosate (3 g/day) and naltrexone (100 mg/day) selected for study, alone and in combination. Pilot 2 was conducted as a feasibility study for the main trial, with the goals of (1) assessing the length of and compliance with research assessments, (2) developing methods for subject recruitment and staff training and (3) assessing the safety of the medications under less controlled outpatient conditions. RESULTS: Results from Pilot 1 provided safety information to support testing the medications in an outpatient study and contributed to the decision to incorporate dose reductions into the main trial protocol to manage adverse events. The results of Pilot 2 formed a basis for (1) reducing the length of the assessment battery, (2) having staff fully trained and recruitment procedures established for the main trial and (3) extending the drug safety results of Pilot 1 to outpatient conditions similar to those of the main trial. CONCLUSIONS: The COMBINE Study provides several examples of the successful application of pilot studies to inform the design of a clinical trial.

Alcoholism↗

PubMed2003

Acamprosate and naltrexone treatment for alcohol dependence: an evidence-based risk-benefits assessment.

This paper provides an evidence-based risk-benefit assessment of acamprosate and naltrexone in the treatment of alcohol dependence. A risk-benefit assessment is based on the premise that the choice of treatment depends on a number of factors, notably the adverse event profile and efficacy. An evidence-based approach attempts to operationalize how such risk-benefit assessments are made to inform physician choices. This approach involves a systematic assessment of all published double-blind, placebo-controlled trials. Based on this review, we conclude acamprosate and naltrexone are both useful in the treatment of alcohol dependence. However, the two drugs act in different ways in the brain, and their clinical profiles are different. Treatment effects seem to be more reliable for acamprosate, and this drug is better tolerated. The safety of the two drugs in combination has been supported by two independent double-blind studies, and combination treatment may offer an advantage for some patients.

Acamprosate↗

PubMed2003

Acamprosate.

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Acamprosate↗

PubMed2002

Rapid and sensitive determination of nalmefene in human plasma by gas chromatography-mass spectrometry.

A rapid gas chromatography-mass spectrometric method for the determination of nalmefene in human plasma is described. The procedure involves protein precipitation, extraction with ethanol-chloroform mixture and derivatization with pentafluropropionic anhydride. The deuterated analog of nalmefene, 6beta-naltrexol-d(7), was used as the internal standard. Quantitation was achieved on a HP-1 column (12 mx0.2 mm I.D.) with negative chemical ionization (NCI) using methane:ammonia (95:5) as the reagent gas. The standard curves were fitted using a quadratic equation with the curve encompassing a range of 0.5 to 200 ng/ml, and the intra- and inter-assay variations for three different nalmefene levels were less than 10% throughout. The limit of quantitation was found to be 0.5 ng/ml. The method described is highly specific and reproducible, and could also be applied for the determination of naltrexone and 6beta-naltrexol. Application of the method to actual human plasma samples is demonstrated.

Gas Chromatography-Mass Spectrometry↗

PubMed2002

A pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone.

Acamprosate and naltrexone have each demonstrated safety and efficacy for alcohol dependence in placebo-controlled clinical trials. There is scientific and clinical interest in evaluating these drugs in combination, given their high tolerability, moderate effect sizes, different pharmacological profiles and potentially different effects on drinking outcomes. Thus, this is the first human pharmacokinetic and pharmacodynamic drug interaction study of acamprosate and naltrexone. Twenty-four normal, healthy adult volunteers participated in a double-blind, multiple dose, within subjects, randomized, 3-way crossover drug interaction study of the standard therapeutic dose of acamprosate (2 g/d) and the standard therapeutic dose of naltrexone (50 mg/d), given alone and in combination, with seven days per treatment condition and seven days washout between treatments. Blood samples were collected on a standardized schedule for pharmacokinetic analysis of naltrexone, 6-beta-naltrexol, and acamprosate. A computerized assessment system evaluated potential drug effects on cognitive functioning. Coadministration of acamprosate with naltrexone significantly increased the rate and extent of absorption of acamprosate, as indicated by an average 33% increase in acamprosate maximum plasma concentration, 33% reduction in time to maximum plasma concentration, and 25% increase in area under the plasma concentration-time curve. Acamprosate did not affect the pharmacokinetic parameters of naltrexone or 6-beta-naltrexol. A complete absence of negative interactions on measures of safety and cognitive function supports the absence of a contraindication to co-administration of acamprosate and naltrexone in clinical practice.

Acamprosate↗

PubMed2002

Potential neuroprotective effects of acamprosate.

This article represents the proceedings of a symposium at the 2001 RSA Meeting in Montreal, Canada. The organizers were Barbara J. Mason and George F. Koob. Anita M. Goodman served as chair. The presentations were (1) Acamprosate inhibits alcohol withdrawal-induced neurotoxicity in organotypic hippocampal cultures, by John Littleton; (2) Acamprosate alteration of NMDA receptor-dependent synaptic transmission and synaptic plasticity, by George R. Siggins; (3) Acamprosate and glutamate during ethanol withdrawal, by Philippe De Witte; (4) Clinical evidence of protective CNS effects of acamprosate in alcohol-dependent individuals, by Barbara J. Mason.

Acamprosate↗